Dianna Roberts | MD Anderson Cancer Center, UT Texas, Houston (original) (raw)

Papers by Dianna Roberts

Research paper thumbnail of Binding of Bacterial Lipopolysaccharide to Murine Lymphocytes

Annals of the New York Academy of Sciences, Jun 1, 1983

Research paper thumbnail of Immunological Comparisons of the Sera of Chicken, Turkey, Pheasant, Quail and Their Intergeneric Hybrids

Poultry Science, 1977

Sera from chicken, turkey, pheasant, quail and their intergeneric hybrids were compared by their ... more Sera from chicken, turkey, pheasant, quail and their intergeneric hybrids were compared by their reactions in two-dimensional immunoelectrophorsis with homologous and heterologous antisera. As many as 44 antigenically distinguishable components were resolved in these sera by use of this technique. Sera from the intergeneric hybrids, when allowed to react with rabbit anti-White Leghorn antiserum, gave more precipitin peaks than did any of the parental sera in reaction with this same antiserum. Thus it appeared that intergeneric hybridization induced a propagation of avian serum antigens recognized by rabbit antiserum to a single parental serum. For example, all parental sera, in reaction with homologous or heterologous antisera, appeared to contain only one precipitin peak which migrated in the albumin area. Sera from the intergeneric hybrids of chicken X turkey, chicken X pheasant, and chicken X quail had two antigenetically distinguishable peaks in the albumin area. Sera from turkey X pheasant and pheasant X quail had only one peak in this region. These results agree with the observations obtained from polyacrylamide disc gel electrophoresis of the plasma proteins.

Research paper thumbnail of Quantitative Promoter Hypermethylation Analysis of Cancer-Related Genes in Salivary Gland Carcinomas: Comparison with Methylation-Specific PCR Technique and Clinical Significance

Clinical Cancer Research, May 1, 2008

To compare the methylation status of tumor-associated genes by quantitative pyrosequencing and qu... more To compare the methylation status of tumor-associated genes by quantitative pyrosequencing and qualitative methylation-specific PCR (MSP) techniques and to correlate the results with clinicopathologic features and patients outcome to determine which method might have greater clinical utility. Experimental Design: The hypermethylation status of the retinoid acid receptor h2 (RARb2), RAS association domain family 1A (RASSF1A), O 6-methylguanine-DNA methyltransferase (MGMT), and E-cadherin genes was analyzed in five salivary carcinoma cell lines and 69 human salivary gland carcinoma specimens by pyrosequencing and MSP techniques. The two datasets were compared by linear regression. Correlations between methods and with clinicopathologic characteristics were assessed by Pearson's m 2 test or the two-tailed Fisher exact test, as applicable, using cutoff points determined from the regression curves and empirical fitting. We also investigated the effect of demethylating agents on methylated genes in cell lines to assess their effect on the expression of these genes. Results: Overall, regression analysis indicated high degrees of correlation of the two methods for measurement of methylation for the RARb2, RASSF1A, and MGMT genes (adjusted R 2 = 0.319, 0.835, and 0.178; P < 0.001, <0.001, and 0.0002, respectively) among the 69 tumors tested. However, the pyrosequencing technique yielded four more instances of methylation above background levels than MSP for RARb2 and three more for RASSF1. Methylation of either RARb2 and RASSF1A alone or both by pyrosequencing were correlated with tumor type (P = 0.027, 0.014, and 0.012, respectively). Methylation of RARb2 alone and in combination with RASSF1A by pyrosequencing were also significantly correlated with tumor grade (P = 0.014 and 0.011, respectively) and 3-year survival (P = 0.002 and 0.004, respectively). The survival curves of patients who had hypermethylation at both RARb2 and RASSF1A were significantly lower than those of patients who had hypermethylation at neither or just for the RASSF1A (P = 0.008 and 0.007, respectively). 5-Azadeoxycytidine treatment of methylated cell lines led to the reactivation of RARb2 expression in only one of the five cell lines. Conclusions: (a) Although the methylation status of RARb2, RASSF1A, and MGMT genes by both techniques were significantly correlated, pyrosequencing is generally more sensitive and its results correlate better with the clinical variables than those of MSP. (b) The methylation level of the RARb2 and/or RASSF1A by pyrosequencing is significantly associated with aggressive tumor phenotypes and patients survival.

Research paper thumbnail of Ocular adnexal lymphoma: validation of American Joint Committee on Cancer seventh edition staging guidelines

British Journal of Ophthalmology, Apr 23, 2014

To validate the prognostic significance of the American Joint Committee on Cancer (AJCC) seventh ... more To validate the prognostic significance of the American Joint Committee on Cancer (AJCC) seventh edition staging criteria for ocular adnexal lymphoma (OAL) of all histologic subtypes. Retrospective review of clinical records for all consecutive patients with OAL treated from November 1998 to December 2012. 130 patients were evaluated, 82 with primary and 34 with secondary OAL. Fourteen patients were excluded due to incomplete records. 71 women (61.2%) and 45 men (38.8%) had a median age of 61.5 years. Patients were followed for a median of 32.5 months. Treatment varied, in part, related to lymphoma histologic subtype. Overall, there were 17 recurrences (8 local and 9 distant) in patients with primary OAL. For primary OAL, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 55.9% and 85.8%, respectively. For primary OAL, while there was a trend towards decreased 5-year DFS for more aggressive subtypes, this was not statistically significant. More advanced Ann Arbor stage was associated with decreased 5-year DFS; however, this trend was not statistically significant. However, increased AJCC seventh edition T category was associated with decreased 5-year DFS (T1=67.8%, T2=59.2%, T3=28.6%, T4=33.3%; p=0.025). AJCC seventh edition T category was predictive of DFS in patients with OAL.

Research paper thumbnail of Cell type-dependent biomarker expression in adenoid cystic carcinoma

Cancer, Sep 7, 2010

Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by c... more Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by cellular, morphologic and clinical heterogeneity. We hypothesize that its dual cellular composition plays an important role in biomarker evaluation, tumor biological behavior and therapy response. To investigate the differential localization and expression of c-kit and EGFR proteins, we performed immunohistochemical analysis on tissue arrays of 199 tumors and correlated the results with the clinico-pathological factors. The results show c-kit expression to be limited to the inner ductal epithelial cells and the EGFR expression mainly to the outer myoepithelial cells in the majority of tubular and cribriform patterns. In solid ACC, c-kit was uniformly positive while EGFR was consistently negative. Significant statistical correlation was found between c-Kit expression and a poor 3-year outcome, and EGFR expression with a better 3-year outcome. Our findings underscore the importance of cellular subtypes' localization of biomarkers in the clinical and therapeutic stratification of patients with this entity.

Research paper thumbnail of Association of TERT Promoter Mutation, But Not BRAF Mutation, With Increased Mortality in PTC

The Journal of Clinical Endocrinology and Metabolism, Dec 1, 2015

Context: Papillary thyroid carcinoma (PTC) carrying the BRAF mutation has been reported to be ass... more Context: Papillary thyroid carcinoma (PTC) carrying the BRAF mutation has been reported to be associated with high recurrence and potentially increased mortality. PTC carrying the TERT promoter mutation has been associated with older age, recurrence, and aggressive disease. Objective: The objective of this study was to determine the association of BRAF and TERT promoter gene alterations with recurrence and survival in a high-risk population. Design: Genomic DNA was analyzed for the BRAF mutation from 256 persistent/recurrent PTC (p/rPTC; 202 new, 54 previously reported) and for the TERT promoter mutation and polymorphism (242 p/rPTC). Two-tailed Fisher exact tests or the Pearson 2 test were performed for the associations between mutations and other variables. Overall and disease-free survivals were compared by log rank tests on Kaplan-Meier plots and by Cox regression analysis. TERT promoter constructs were tested in PTC cell lines to determine their activities in these cells. Results: BRAF V600E mutation was identified in 235 of 256 (91.8%), TERT promoter mutation at Ϫ124 was detected in 77 of 242 (31.8%), and TERT promoter polymorphism at Ϫ245 was found in 113 of 242 (46.7%) p/rPTC patients. A significant difference in survival was found in p/rPTC patients with the TERT promoter mutation, which also displayed increased activity in vitro as compared to the nonmutated promoter sequence. No association was noted between the BRAF mutation or TERT promoter polymorphism and recurrence or survival. A drawback of our study could be the limited number of patients with nonmutated BRAF (21 of 256 [8.2%]). Conclusions: Mutation in the TERT promoter, but not in BRAF, was associated with decreased survival in 19 (24.7%) p/rPTC patients who died of disease and in 38 (49.4%) p/rPTC patients who died at last contact. The presence or absence of the BRAF mutation and TERT promoter polymorphism, however, was not significantly correlated with survival.

Research paper thumbnail of Sentinel node biopsy in patients with cutaneous melanoma of the head and neck: Recurrence and survival study

Head & neck, Oct 1, 2008

Background. Controversy remains regarding the benefits of sentinel lymph node (SLN) biopsy for pr... more Background. Controversy remains regarding the benefits of sentinel lymph node (SLN) biopsy for predicting survival in cutaneous melanoma of the head and neck (CMHN). Methods. We analyzed the factors associated with the recurrence and survival of CMHN patients treated in our institution. Results. One hundred thirteen patients underwent SLN biopsy for CMHN in a 12-year period. SLN identification was successful in 96%, with a median of 3 SLNs per patient. Positive-SLNs were identified in 21%. With a median follow-up of 34 months, 28% recurred. Disease-free survival (DFS) and overall survival (OS) rates were 66% and 78% in patients with SLN-negative, and 39% and 62% in SLN-positive disease. In multivariate analysis, greater Breslow-thickness was associated with decreased DFS rate (HR 2.07, CI 1.04-4.09), and age >60 years (HR 3.53, CI 1.32-9.4) with lower 5-year OS rate. Conclusion. Primary tumor thickness and age were associated with decreased survival, whereas SLN status showed a trend for prognostic significance in CMHN. V

Research paper thumbnail of Histologic features of conjunctival melanoma predictive of metastasis and death (an American Ophthalmological thesis)

PubMed, Dec 1, 2012

Purpose: In conjunctival melanoma, tumor thickness and nonlimbal location are associated with poo... more Purpose: In conjunctival melanoma, tumor thickness and nonlimbal location are associated with poor prognosis. However, other established high-risk features for cutaneous melanoma, including ulceration, mitotic figures, epithelioid cell type, and lymphovascular invasion, have not previously been studied extensively for their prognostic value in conjunctival melanoma. We examined the hypothesis that these features also predict regional nodal metastasis and death in conjunctival melanoma. Methods: The medical records of 44 of 46 consecutive conjunctival melanoma patients treated between June 2003 and December 2009 were retrospectively reviewed; tumor tissue was not available for the two excluded patients. Demographic and clinicopathologic features, including tumor location, tumor thickness, ulceration, mitotic rate, histology, lymphovascular invasion, and microsatellitosis, were reviewed. Outcome measures included regional nodal metastasis, distant metastasis, and death. Results: Twenty-six women and 18 men had a median age of 62 years. Regional nodal metastasis occurred in 7 patients (16%) and distant metastasis in 9 (20%). Median follow-up was 40 months. At last follow-up, 10 patients (23%) had died of disease. Tumor thickness>2.0 mm, ulceration, and mitotic figure>1/mm2 predicted regional nodal metastasis and death from disease. In addition to these three histologic features, vascular invasion, epithelioid cell type, and microsatellitosis significantly predicted death from disease. Tumor location (bulbar vs nonbulbar) was not correlated with regional nodal metastasis or death. Conclusions: In conjunctival melanoma, as in cutaneous melanoma, thicker tumor, ulceration, and higher mitotic rate are correlated with regional nodal metastasis. In addition, lymphovascular invasion, epithelioid cell type, and microsatellitosis are correlated with melanoma-related death.

Research paper thumbnail of An audit and feedback system for effective quality improvement in head and neck surgery: Can we become better surgeons?

Cancer, Jan 13, 2015

Background-We have established an evaluation system for measuring physician performance. We aimed... more Background-We have established an evaluation system for measuring physician performance. We aimed to determine whether initial evaluation with surgeon feedback improved subsequent performance. Methods-After evaluation of the initial cohort of procedures (2004-2008), surgeons were given risk-adjusted individual feedback. Procedures in the post-feedback cohort (2009-2010) were then assessed. Both groups were further stratified into high-and low-acuity procedures (HAPs and LAPs, respectively). Negative performance measures included length of peri-operative stay longer than 2 days for LAPs and 11 days for HAPs, peri-operative blood transfusion, return to the operating room within 7 days and readmission, surgical site infection, and mortality within 30 days. Results-There were 2618 procedures in the initial cohort and 1389 procedures in the postfeedback cohort. Factors affecting performance included surgeon, procedure acuity, and patient co-morbidities. There were no significant differences in the proportion of LAPs and HAPs or in the prevalence of patient co-morbidities between the 2 assessment periods. Mean length of stay significantly decreased for LAPs from 2.1 to 1.5 days (p=0.005) and for HAPs from 10.5 to 7 days (p=0.003). The incidence of having one or more negative performance indicators decreased significantly for LAPs from 39.1% to 28.6% (p<0.001) and trended down for HAPs from 60.9% to 53.5% (p=.081). Conclusions-Periodic assessment of performance and outcomes are essential to continual quality improvement. Significant decreases in length of stay and negative performance indicators were seen after feedback. We conclude that an audit and feedback system may be an effective means of improving quality of care as well as reducing practice variability within a surgical department.

Research paper thumbnail of The role of interstitial brachytherapy with salvage surgery for the management of recurrent head and neck cancers

Research paper thumbnail of Role of<i>CRTC1/MAML2</i>Translocation in the Prognosis and Clinical Outcomes of Mucoepidermoid Carcinoma

JAMA otolaryngology-- head & neck surgery, Mar 1, 2016

IMPORTANCE The CRTC1/MAML2 fusion transcript, which arises from the CRTC1/MAML2 translocation, is... more IMPORTANCE The CRTC1/MAML2 fusion transcript, which arises from the CRTC1/MAML2 translocation, is a molecular marker unique to mucoepidermoid carcinoma (MEC), the most common malignant tumor of the salivary gland. The extent to which the transcript influences disease features and patient survival is unclear. OBJECTIVE To determine whether the CRTC1/MAML2 fusion transcript is associated with disease stage, tumor grade, or survival outcomes in patients with MEC. DESIGN, SETTING, AND PARTICIPANTS A retrospective medical record review was performed at a tertiary-care academic medical institution. The review included 90 patients with MEC who underwent treatment from January 1, 1995, to December 31, 2011, and for whom archived formalin-fixed, paraffin-embedded tumor specimens were available. Records were reviewed for clinical, demographic, and survival data. Tumor specimens underwent fluorescence in situ hybridization. Follow-up was completed on May 15, 2014, and data were analyzed from June 1 to July 1, 2014. MAIN OUTCOMES AND MEASURES CRTC1/MAML2 fusion transcript status. Statistical analysis determined whether transcript status was associated with disease stage, tumor grade, and/or overall and disease-free survival. RESULTS Among the 90 eligible patients (median [range] age, 55.1 [7.8-89.2] years), 42 were female and 48 were male. Fluorescence in situ hybridization revealed a CRTC1/MAML2 translocation in 50 patients (56%). The translocations were more prevalent in intermediate-grade tumors (31 of 49 [63%]) than in high-grade (11 of 49 [22%]) and low-grade (7 of 49 [14%]) tumors; 1 tumor sample had no available grading. Similar proportions of patients with translocation-positive disease had T1 (13 of 49 [26%]), T2 (15 of 49 [31%]), T4a (14 of 49 [28%]), or T0 or Tx (8 of 49 [16%]) stages of disease. Thirty-eight of 49 patients with translocation-positive MEC (78%) had N0 stage of disease. Rates of 5-year overall survival were similar for patients with translocation-positive and translocationnegative disease (76.8% vs 75.5%, respectively; P = .17), as were rates of disease-free survival (65.2% vs 57.4%, respectively; P = .28). CONCLUSIONS AND RELEVANCE Detection of the CRTC1/MAML2 fusion transcript provides useful information for MEC diagnosis but is not associated with differences in survival outcomes.

Research paper thumbnail of Malignant Fibrous Histiocytoma of the Head and Neck Region

Laryngoscope, 2009

ABSTRACT

Research paper thumbnail of Sialendoscopy for Patients with Radioiodine-Induced Sialadenitis and Xerostomia

Thyroid, Jul 1, 2015

Background: We examined outcomes in patients treated for radioactive iodine-induced sialadenitis ... more Background: We examined outcomes in patients treated for radioactive iodine-induced sialadenitis (RAIS) and xerostomia with sialendoscopy. Methods: Data was prospectively collected for all patients undergoing sialendoscopy for RAIS from a single institution. Interventional details and intraoperative findings were recorded. Qualitative data were obtained through patient examination, telephone interviews, and use of a standard quality of life questionnaire, Xerostomia Questionnaire. Quantitative data were obtained from patients who underwent sialometry. Results: Twenty-six patients (24 women and 2 men; median age, 43 years; age range, 19-57 years) underwent interventional sialendoscopy after conservative management of symptoms proved unsuccessful. Sialadenitis was present in 25 patients and xerostomia in 22 patients. Mucus plugging in the duct of the gland was the most common finding (22 patients) followed by stenosis (18 patients), inflammation (eight patients), and erythema (eight patients). Median follow-up time was 23.4-12.1 months. Sixteen patients (64%) reported complete resolution; seven (28%), partial resolution; one (4%), no change in symptoms; and one (4%), regression in RAIS-related symptoms. Patients subjectively noted the following regarding their xerostomia symptoms: seven (31.8%) had complete resolution; 10 (45.5%), partial resolution; four (18.2%), no change; and one (4.5%), regression. Statistical analysis of the available sialometry data revealed a statistically significant difference in saliva production at 6 months following sialendoscopy for unstimulated saliva production (p = 0.028). Conclusion: Sialendoscopy is an effective treatment option for the management of RAIS and xerostomia refractory to conservative therapy and medical management. Patients in our cohort report durable improvement in symptoms after intervention.

Research paper thumbnail of Outcomes of Pediatric Patients with Malignancies of the Major Salivary Glands

Annals of Surgical Oncology, Jun 29, 2010

Background.-To report the outcomes and early to long term treatment complications among pediatric... more Background.-To report the outcomes and early to long term treatment complications among pediatric patients with major salivary gland malignancies treated at a single institution. Materials and Method.-This study was a retrospective case review set at a tertiary referral cancer center. Patients less than 19 years of age with a diagnosis of a major salivary gland malignancy were identified at the M. D. Anderson tumor database between 1953 and 2006. Results.-A total of 61 patients were identified, with equal gender distribution. The majority of tumors arose in the parotid gland (83%), and the most common pathology was mucoepidermoid carcinoma (46%). Lymphatic metastasis was identified in 37% of patients, nearly all with mucoepidermoid carcinoma. Although 65% of patients had prior treatment elsewhere, more than 75% of patients underwent surgical resection at our institution. External beam radiation was used in 45% of patients, with an average dose of 58.6 Gray. Average patient follow-up was 153 months. The overall survival rate was 93% at 5 years, and 26% developed a recurrence. A second primary was identified in 2 patients. Permanent facial paresis was noted in 7 patients (12%) and xerostomia in 1 patient (4%). Conclusions.-Survival of pediatric patients with major salivary gland carcinomas is favorable. Adverse outcomes were best predicted by tumor grade, margin status, and neural involvement. Radiation therapy is beneficial for locoregional control of disease, with acceptable long-term FIGURE 1.-a Distribution of pediatric major salivary gland tumors by histology. (Reprinted from Kupferman ME, de la Garza GO, Santillan AA, et al. Outcomes of pediatric patients with malignancies of the major salivary glands. Ann Surg Oncol. 2010;[Epub ahead of print], with kind permission from Springer Science+Business Media: Annals of Surgical Oncology.

Research paper thumbnail of Genetic and Expression Analysis of HER-2 and EGFR Genes in Salivary Duct Carcinoma: Empirical and Therapeutic Significance

Clinical Cancer Research, Apr 14, 2010

Purpose: Salivary duct carcinoma overexpresses epidermal growth factor receptor (EGFR) and HER-2,... more Purpose: Salivary duct carcinoma overexpresses epidermal growth factor receptor (EGFR) and HER-2, although the underlying mechanisms remain undefined. Because of the potential utilization of these markers as treatment targets, we evaluated protein and gene status by several techniques to determine complementary value. Experimental Design: A tissue microarray of 66 salivary duct carcinomas was used for immunohistochemical analysis of HER-2 and EGFR expression (semiquantitatively evaluated into a three-tiered system), and fluorescence in situ hybridization for gene copy number, and chromosomes 7 and 17 ploidy status. Sequencing of exons 18, 19, and 21 of the EGFR gene for mutations was carried out. Result: For EGFR, 46 (69.7%) of the 66 tumors showed some form of EGFR expression (17 at 3+, 17 at 2+, 12 at 1+) but none gene amplification. Five (9.4%) of 53 tumors showed mutations in exon 18 (n = 3) and exon 19 (n = 2). Polysomy of chromosome 7 (average >2.5 copies/cell) was detected in 15 (25.0%) of 60 tumors (6 at 3+, 5 at 2+, 2 at 1+, 2 at 0+ expression) and correlated with poor 3-year survival (P = 0.015). For HER-2, 17 (25.8%) of 66 tumors expressed HER-2 (10 at 3+, 3 at 2+, 4 at 1+). Eight tumors showed HER-2 gene amplification (6 at 3+, 1 at 1+, 1 at 0+ protein expression). Chromosome 17 polysomy was found in 8 (15.7%) of 51 tumors; two had HER-2 expression (3+, 1+). Conclusion: Our study shows that salivary duct carcinomas (a) harbor EGFR gene mutations in a subset of tumors that may guide therapy, (b) pursue an aggressive clinical course in cases with chromosome 7 polysomy and high EGFR expression, and (c) with HER-2 gene amplification and protein high expression, may be selected for targeted therapy. Clin Cancer Res; 16(8); 2266-74. ©2010 AACR.

Research paper thumbnail of The role of postoperative adjuvant radiation therapy in the treatment of mucosal melanomas of the head and neck region

Archives of Otolaryngology-head & Neck Surgery, Aug 1, 2003

Research paper thumbnail of Differential Expression of Hormonal and Growth Factor Receptors in Salivary Duct Carcinomas

The American Journal of Surgical Pathology, Nov 1, 2007

Research paper thumbnail of Presence of malignant tumor cells in persistent neck disease after radiotherapy for advanced squamous cell carcinoma of the oropharynx is associated with poor survival

European Archives of Oto-rhino-laryngology, Nov 22, 2005

Non-surgical therapy consisting of external beam radiation with or without chemotherapy is an eff... more Non-surgical therapy consisting of external beam radiation with or without chemotherapy is an effective treatment for patients with squamous cell carcinoma (SCC) of the oropharynx with advanced neck disease (N2a or greater). However, many of these patients have to undergo a neck dissection for clinically persistent regional disease. It is reported that nearly 50% of the neck dissection specimens contain residual viable tumor cells that may indicate partial radiation failure and as a consequence poor survival. In order to address the significance of this finding, we conducted a nonrandomized retrospective study, including 35 patients who underwent definitive radiation therapy followed by either a radical or modified radical (RND/MRND) or a selective neck dissection (SND) for clinically persistent neck disease 6 weeks after completing therapy for stage III/IV SCC of the oropharynx (base of the tongue =15, tonsil =12, soft palate =7 and pharyngeal wall =1). All neck dissection specimens were reviewed according to histological criteria indicating viable residual tumor. We observed an increased relative risk (RR) for local and regional failures in the patient population with viable cancer cells in the post-irradiation neck specimens (RR=6.7 and 4.1, respectively). The presence of malignant tumor cells in residual disease in the neck correlated with poor disease-specific and overall survival (P =0.03 and P =0.01, respectively). Of note, the extent of neck dissection did not improve the disease-free or overall survival in this patient population (P =0.5 and P =0.6, respectively). In conclusion, the presence of viable cancer cells in radiated neck nodes is a novel prognostic marker for disease-specific survival in patients treated for SCCs of the oropharynx with advanced neck disease and may serve as an identifier for patients who will benefit from post-treatment chemoprevention.

Research paper thumbnail of Molecular and Clinicopathologic Comparisons of Head and Neck Squamous Carcinoma Variants

The American Journal of Surgical Pathology, Oct 1, 2004

To investigate, for the first time, the events associated with the phenotypic and clinical divers... more To investigate, for the first time, the events associated with the phenotypic and clinical diversities of head and neck squamous carcinomas (HNSC), we performed molecular analyses on 92 primary tumors representing the entire spectrum of the morphologic subtypes using microsatellite markers at chromosome 3p, 4p, 8p, 9p, 11q, 17p, and 18q regions and correlated the results with the clinicopathologic features and patients' survival. Loss of heterozygosity (LOH) at D9S168 and D9S171 markers on chromosome 9p regions was commonly identified in all subtypes. Distinctive alterations in certain subtypes were noted at chromosomes 3p, 4p, 8p, and 11p regions. In general, less aggressive types (verrucous, papillary, and well-differentiated conventional) had a significantly lower LOH incidence than the more aggressive (basaloid, sarcomatoid, and highgrade conventional squamous carcinoma) categories. Significant association between LOH and age, stage, nodal status, and patient outcome was found. Survival analysis revealed that pathologic categorization (less versus more aggressive) and LOH at marker D11S4167 and D3S2432 are independent predictors of patients' survival. Our analysis also defined a set of limited markers that account for most of alterations within and across these tumor subtypes. Our study indicates that 1) certain genetic markers are common to all subtypes of HNSC supporting their early involvement in tumorigenesis, 2) inter-and intratumoral genetic differences evolve subsequently and may underlie their morphologic heterogeneity, 3) high incidence of LOH in certain regions characterizes aggressive tumors, 4) categorical classification and LOH at 11p and 3p regions independently correlated with patient survival, and 5) a limited set of markers identify the majority of genetic alterations in these tumors.

Research paper thumbnail of Moderately Differentiated Neuroendocrine Carcinoma (Atypical Carcinoid) of the Larynx: A Clinically Aggressive Tumor

Laryngoscope, Jul 1, 2005

To evaluate the presentation, treatment, and outcome of a small series of patients with moderatel... more To evaluate the presentation, treatment, and outcome of a small series of patients with moderately differentiated neuroendocrine carcinoma (MDNC) of the larynx seen at one institution and to provide information on this uncommon laryngeal malignancy for therapeutic decision making. Retrospective analysis of medical records. Cases were identified from databases maintained by the medical informatics and pathology departments. Patient, tumor, treatment, and outcome data were collected from medical records. Main outcome measures were recurrence, overall and disease-specific survival, and cause of death. Eleven patients (6 males; 5 females) seen between 1990 and 2003 had sufficient documentation for further evaluation. Patients presented with dysphagia, throat pain, or hoarseness, and all tumors arose in the supraglottis. Eight of 11 patients gave a history of cigarette use. Of the 10 patients treated with curative intent, 7 who recurred all died with disease. The average disease-free interval was 54 months, with a range of 2 to 101 months. The overall and disease-specific survival was 64 and 54 months, respectively. Nine patients were alive 3 years after diagnosis. No correlations with age, stage at presentation, or initial treatment modality and outcome (recurrence or survival) were found. Laryngeal MDNC is an aggressive malignancy with frequent regional and distant metastases. Although surgical resection is usually recommended, patients did respond to radiation and chemotherapy, suggesting a combined approach may be indicated. Aggressive initial therapy is needed because development of recurrence portends a poor outcome.

Research paper thumbnail of Binding of Bacterial Lipopolysaccharide to Murine Lymphocytes

Annals of the New York Academy of Sciences, Jun 1, 1983

Research paper thumbnail of Immunological Comparisons of the Sera of Chicken, Turkey, Pheasant, Quail and Their Intergeneric Hybrids

Poultry Science, 1977

Sera from chicken, turkey, pheasant, quail and their intergeneric hybrids were compared by their ... more Sera from chicken, turkey, pheasant, quail and their intergeneric hybrids were compared by their reactions in two-dimensional immunoelectrophorsis with homologous and heterologous antisera. As many as 44 antigenically distinguishable components were resolved in these sera by use of this technique. Sera from the intergeneric hybrids, when allowed to react with rabbit anti-White Leghorn antiserum, gave more precipitin peaks than did any of the parental sera in reaction with this same antiserum. Thus it appeared that intergeneric hybridization induced a propagation of avian serum antigens recognized by rabbit antiserum to a single parental serum. For example, all parental sera, in reaction with homologous or heterologous antisera, appeared to contain only one precipitin peak which migrated in the albumin area. Sera from the intergeneric hybrids of chicken X turkey, chicken X pheasant, and chicken X quail had two antigenetically distinguishable peaks in the albumin area. Sera from turkey X pheasant and pheasant X quail had only one peak in this region. These results agree with the observations obtained from polyacrylamide disc gel electrophoresis of the plasma proteins.

Research paper thumbnail of Quantitative Promoter Hypermethylation Analysis of Cancer-Related Genes in Salivary Gland Carcinomas: Comparison with Methylation-Specific PCR Technique and Clinical Significance

Clinical Cancer Research, May 1, 2008

To compare the methylation status of tumor-associated genes by quantitative pyrosequencing and qu... more To compare the methylation status of tumor-associated genes by quantitative pyrosequencing and qualitative methylation-specific PCR (MSP) techniques and to correlate the results with clinicopathologic features and patients outcome to determine which method might have greater clinical utility. Experimental Design: The hypermethylation status of the retinoid acid receptor h2 (RARb2), RAS association domain family 1A (RASSF1A), O 6-methylguanine-DNA methyltransferase (MGMT), and E-cadherin genes was analyzed in five salivary carcinoma cell lines and 69 human salivary gland carcinoma specimens by pyrosequencing and MSP techniques. The two datasets were compared by linear regression. Correlations between methods and with clinicopathologic characteristics were assessed by Pearson's m 2 test or the two-tailed Fisher exact test, as applicable, using cutoff points determined from the regression curves and empirical fitting. We also investigated the effect of demethylating agents on methylated genes in cell lines to assess their effect on the expression of these genes. Results: Overall, regression analysis indicated high degrees of correlation of the two methods for measurement of methylation for the RARb2, RASSF1A, and MGMT genes (adjusted R 2 = 0.319, 0.835, and 0.178; P < 0.001, <0.001, and 0.0002, respectively) among the 69 tumors tested. However, the pyrosequencing technique yielded four more instances of methylation above background levels than MSP for RARb2 and three more for RASSF1. Methylation of either RARb2 and RASSF1A alone or both by pyrosequencing were correlated with tumor type (P = 0.027, 0.014, and 0.012, respectively). Methylation of RARb2 alone and in combination with RASSF1A by pyrosequencing were also significantly correlated with tumor grade (P = 0.014 and 0.011, respectively) and 3-year survival (P = 0.002 and 0.004, respectively). The survival curves of patients who had hypermethylation at both RARb2 and RASSF1A were significantly lower than those of patients who had hypermethylation at neither or just for the RASSF1A (P = 0.008 and 0.007, respectively). 5-Azadeoxycytidine treatment of methylated cell lines led to the reactivation of RARb2 expression in only one of the five cell lines. Conclusions: (a) Although the methylation status of RARb2, RASSF1A, and MGMT genes by both techniques were significantly correlated, pyrosequencing is generally more sensitive and its results correlate better with the clinical variables than those of MSP. (b) The methylation level of the RARb2 and/or RASSF1A by pyrosequencing is significantly associated with aggressive tumor phenotypes and patients survival.

Research paper thumbnail of Ocular adnexal lymphoma: validation of American Joint Committee on Cancer seventh edition staging guidelines

British Journal of Ophthalmology, Apr 23, 2014

To validate the prognostic significance of the American Joint Committee on Cancer (AJCC) seventh ... more To validate the prognostic significance of the American Joint Committee on Cancer (AJCC) seventh edition staging criteria for ocular adnexal lymphoma (OAL) of all histologic subtypes. Retrospective review of clinical records for all consecutive patients with OAL treated from November 1998 to December 2012. 130 patients were evaluated, 82 with primary and 34 with secondary OAL. Fourteen patients were excluded due to incomplete records. 71 women (61.2%) and 45 men (38.8%) had a median age of 61.5 years. Patients were followed for a median of 32.5 months. Treatment varied, in part, related to lymphoma histologic subtype. Overall, there were 17 recurrences (8 local and 9 distant) in patients with primary OAL. For primary OAL, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 55.9% and 85.8%, respectively. For primary OAL, while there was a trend towards decreased 5-year DFS for more aggressive subtypes, this was not statistically significant. More advanced Ann Arbor stage was associated with decreased 5-year DFS; however, this trend was not statistically significant. However, increased AJCC seventh edition T category was associated with decreased 5-year DFS (T1=67.8%, T2=59.2%, T3=28.6%, T4=33.3%; p=0.025). AJCC seventh edition T category was predictive of DFS in patients with OAL.

Research paper thumbnail of Cell type-dependent biomarker expression in adenoid cystic carcinoma

Cancer, Sep 7, 2010

Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by c... more Adenoid cystic carcinoma (ACC), a rare and progressive salivary malignancy, is characterized by cellular, morphologic and clinical heterogeneity. We hypothesize that its dual cellular composition plays an important role in biomarker evaluation, tumor biological behavior and therapy response. To investigate the differential localization and expression of c-kit and EGFR proteins, we performed immunohistochemical analysis on tissue arrays of 199 tumors and correlated the results with the clinico-pathological factors. The results show c-kit expression to be limited to the inner ductal epithelial cells and the EGFR expression mainly to the outer myoepithelial cells in the majority of tubular and cribriform patterns. In solid ACC, c-kit was uniformly positive while EGFR was consistently negative. Significant statistical correlation was found between c-Kit expression and a poor 3-year outcome, and EGFR expression with a better 3-year outcome. Our findings underscore the importance of cellular subtypes' localization of biomarkers in the clinical and therapeutic stratification of patients with this entity.

Research paper thumbnail of Association of TERT Promoter Mutation, But Not BRAF Mutation, With Increased Mortality in PTC

The Journal of Clinical Endocrinology and Metabolism, Dec 1, 2015

Context: Papillary thyroid carcinoma (PTC) carrying the BRAF mutation has been reported to be ass... more Context: Papillary thyroid carcinoma (PTC) carrying the BRAF mutation has been reported to be associated with high recurrence and potentially increased mortality. PTC carrying the TERT promoter mutation has been associated with older age, recurrence, and aggressive disease. Objective: The objective of this study was to determine the association of BRAF and TERT promoter gene alterations with recurrence and survival in a high-risk population. Design: Genomic DNA was analyzed for the BRAF mutation from 256 persistent/recurrent PTC (p/rPTC; 202 new, 54 previously reported) and for the TERT promoter mutation and polymorphism (242 p/rPTC). Two-tailed Fisher exact tests or the Pearson 2 test were performed for the associations between mutations and other variables. Overall and disease-free survivals were compared by log rank tests on Kaplan-Meier plots and by Cox regression analysis. TERT promoter constructs were tested in PTC cell lines to determine their activities in these cells. Results: BRAF V600E mutation was identified in 235 of 256 (91.8%), TERT promoter mutation at Ϫ124 was detected in 77 of 242 (31.8%), and TERT promoter polymorphism at Ϫ245 was found in 113 of 242 (46.7%) p/rPTC patients. A significant difference in survival was found in p/rPTC patients with the TERT promoter mutation, which also displayed increased activity in vitro as compared to the nonmutated promoter sequence. No association was noted between the BRAF mutation or TERT promoter polymorphism and recurrence or survival. A drawback of our study could be the limited number of patients with nonmutated BRAF (21 of 256 [8.2%]). Conclusions: Mutation in the TERT promoter, but not in BRAF, was associated with decreased survival in 19 (24.7%) p/rPTC patients who died of disease and in 38 (49.4%) p/rPTC patients who died at last contact. The presence or absence of the BRAF mutation and TERT promoter polymorphism, however, was not significantly correlated with survival.

Research paper thumbnail of Sentinel node biopsy in patients with cutaneous melanoma of the head and neck: Recurrence and survival study

Head & neck, Oct 1, 2008

Background. Controversy remains regarding the benefits of sentinel lymph node (SLN) biopsy for pr... more Background. Controversy remains regarding the benefits of sentinel lymph node (SLN) biopsy for predicting survival in cutaneous melanoma of the head and neck (CMHN). Methods. We analyzed the factors associated with the recurrence and survival of CMHN patients treated in our institution. Results. One hundred thirteen patients underwent SLN biopsy for CMHN in a 12-year period. SLN identification was successful in 96%, with a median of 3 SLNs per patient. Positive-SLNs were identified in 21%. With a median follow-up of 34 months, 28% recurred. Disease-free survival (DFS) and overall survival (OS) rates were 66% and 78% in patients with SLN-negative, and 39% and 62% in SLN-positive disease. In multivariate analysis, greater Breslow-thickness was associated with decreased DFS rate (HR 2.07, CI 1.04-4.09), and age >60 years (HR 3.53, CI 1.32-9.4) with lower 5-year OS rate. Conclusion. Primary tumor thickness and age were associated with decreased survival, whereas SLN status showed a trend for prognostic significance in CMHN. V

Research paper thumbnail of Histologic features of conjunctival melanoma predictive of metastasis and death (an American Ophthalmological thesis)

PubMed, Dec 1, 2012

Purpose: In conjunctival melanoma, tumor thickness and nonlimbal location are associated with poo... more Purpose: In conjunctival melanoma, tumor thickness and nonlimbal location are associated with poor prognosis. However, other established high-risk features for cutaneous melanoma, including ulceration, mitotic figures, epithelioid cell type, and lymphovascular invasion, have not previously been studied extensively for their prognostic value in conjunctival melanoma. We examined the hypothesis that these features also predict regional nodal metastasis and death in conjunctival melanoma. Methods: The medical records of 44 of 46 consecutive conjunctival melanoma patients treated between June 2003 and December 2009 were retrospectively reviewed; tumor tissue was not available for the two excluded patients. Demographic and clinicopathologic features, including tumor location, tumor thickness, ulceration, mitotic rate, histology, lymphovascular invasion, and microsatellitosis, were reviewed. Outcome measures included regional nodal metastasis, distant metastasis, and death. Results: Twenty-six women and 18 men had a median age of 62 years. Regional nodal metastasis occurred in 7 patients (16%) and distant metastasis in 9 (20%). Median follow-up was 40 months. At last follow-up, 10 patients (23%) had died of disease. Tumor thickness>2.0 mm, ulceration, and mitotic figure>1/mm2 predicted regional nodal metastasis and death from disease. In addition to these three histologic features, vascular invasion, epithelioid cell type, and microsatellitosis significantly predicted death from disease. Tumor location (bulbar vs nonbulbar) was not correlated with regional nodal metastasis or death. Conclusions: In conjunctival melanoma, as in cutaneous melanoma, thicker tumor, ulceration, and higher mitotic rate are correlated with regional nodal metastasis. In addition, lymphovascular invasion, epithelioid cell type, and microsatellitosis are correlated with melanoma-related death.

Research paper thumbnail of An audit and feedback system for effective quality improvement in head and neck surgery: Can we become better surgeons?

Cancer, Jan 13, 2015

Background-We have established an evaluation system for measuring physician performance. We aimed... more Background-We have established an evaluation system for measuring physician performance. We aimed to determine whether initial evaluation with surgeon feedback improved subsequent performance. Methods-After evaluation of the initial cohort of procedures (2004-2008), surgeons were given risk-adjusted individual feedback. Procedures in the post-feedback cohort (2009-2010) were then assessed. Both groups were further stratified into high-and low-acuity procedures (HAPs and LAPs, respectively). Negative performance measures included length of peri-operative stay longer than 2 days for LAPs and 11 days for HAPs, peri-operative blood transfusion, return to the operating room within 7 days and readmission, surgical site infection, and mortality within 30 days. Results-There were 2618 procedures in the initial cohort and 1389 procedures in the postfeedback cohort. Factors affecting performance included surgeon, procedure acuity, and patient co-morbidities. There were no significant differences in the proportion of LAPs and HAPs or in the prevalence of patient co-morbidities between the 2 assessment periods. Mean length of stay significantly decreased for LAPs from 2.1 to 1.5 days (p=0.005) and for HAPs from 10.5 to 7 days (p=0.003). The incidence of having one or more negative performance indicators decreased significantly for LAPs from 39.1% to 28.6% (p<0.001) and trended down for HAPs from 60.9% to 53.5% (p=.081). Conclusions-Periodic assessment of performance and outcomes are essential to continual quality improvement. Significant decreases in length of stay and negative performance indicators were seen after feedback. We conclude that an audit and feedback system may be an effective means of improving quality of care as well as reducing practice variability within a surgical department.

Research paper thumbnail of The role of interstitial brachytherapy with salvage surgery for the management of recurrent head and neck cancers

Research paper thumbnail of Role of<i>CRTC1/MAML2</i>Translocation in the Prognosis and Clinical Outcomes of Mucoepidermoid Carcinoma

JAMA otolaryngology-- head & neck surgery, Mar 1, 2016

IMPORTANCE The CRTC1/MAML2 fusion transcript, which arises from the CRTC1/MAML2 translocation, is... more IMPORTANCE The CRTC1/MAML2 fusion transcript, which arises from the CRTC1/MAML2 translocation, is a molecular marker unique to mucoepidermoid carcinoma (MEC), the most common malignant tumor of the salivary gland. The extent to which the transcript influences disease features and patient survival is unclear. OBJECTIVE To determine whether the CRTC1/MAML2 fusion transcript is associated with disease stage, tumor grade, or survival outcomes in patients with MEC. DESIGN, SETTING, AND PARTICIPANTS A retrospective medical record review was performed at a tertiary-care academic medical institution. The review included 90 patients with MEC who underwent treatment from January 1, 1995, to December 31, 2011, and for whom archived formalin-fixed, paraffin-embedded tumor specimens were available. Records were reviewed for clinical, demographic, and survival data. Tumor specimens underwent fluorescence in situ hybridization. Follow-up was completed on May 15, 2014, and data were analyzed from June 1 to July 1, 2014. MAIN OUTCOMES AND MEASURES CRTC1/MAML2 fusion transcript status. Statistical analysis determined whether transcript status was associated with disease stage, tumor grade, and/or overall and disease-free survival. RESULTS Among the 90 eligible patients (median [range] age, 55.1 [7.8-89.2] years), 42 were female and 48 were male. Fluorescence in situ hybridization revealed a CRTC1/MAML2 translocation in 50 patients (56%). The translocations were more prevalent in intermediate-grade tumors (31 of 49 [63%]) than in high-grade (11 of 49 [22%]) and low-grade (7 of 49 [14%]) tumors; 1 tumor sample had no available grading. Similar proportions of patients with translocation-positive disease had T1 (13 of 49 [26%]), T2 (15 of 49 [31%]), T4a (14 of 49 [28%]), or T0 or Tx (8 of 49 [16%]) stages of disease. Thirty-eight of 49 patients with translocation-positive MEC (78%) had N0 stage of disease. Rates of 5-year overall survival were similar for patients with translocation-positive and translocationnegative disease (76.8% vs 75.5%, respectively; P = .17), as were rates of disease-free survival (65.2% vs 57.4%, respectively; P = .28). CONCLUSIONS AND RELEVANCE Detection of the CRTC1/MAML2 fusion transcript provides useful information for MEC diagnosis but is not associated with differences in survival outcomes.

Research paper thumbnail of Malignant Fibrous Histiocytoma of the Head and Neck Region

Laryngoscope, 2009

ABSTRACT

Research paper thumbnail of Sialendoscopy for Patients with Radioiodine-Induced Sialadenitis and Xerostomia

Thyroid, Jul 1, 2015

Background: We examined outcomes in patients treated for radioactive iodine-induced sialadenitis ... more Background: We examined outcomes in patients treated for radioactive iodine-induced sialadenitis (RAIS) and xerostomia with sialendoscopy. Methods: Data was prospectively collected for all patients undergoing sialendoscopy for RAIS from a single institution. Interventional details and intraoperative findings were recorded. Qualitative data were obtained through patient examination, telephone interviews, and use of a standard quality of life questionnaire, Xerostomia Questionnaire. Quantitative data were obtained from patients who underwent sialometry. Results: Twenty-six patients (24 women and 2 men; median age, 43 years; age range, 19-57 years) underwent interventional sialendoscopy after conservative management of symptoms proved unsuccessful. Sialadenitis was present in 25 patients and xerostomia in 22 patients. Mucus plugging in the duct of the gland was the most common finding (22 patients) followed by stenosis (18 patients), inflammation (eight patients), and erythema (eight patients). Median follow-up time was 23.4-12.1 months. Sixteen patients (64%) reported complete resolution; seven (28%), partial resolution; one (4%), no change in symptoms; and one (4%), regression in RAIS-related symptoms. Patients subjectively noted the following regarding their xerostomia symptoms: seven (31.8%) had complete resolution; 10 (45.5%), partial resolution; four (18.2%), no change; and one (4.5%), regression. Statistical analysis of the available sialometry data revealed a statistically significant difference in saliva production at 6 months following sialendoscopy for unstimulated saliva production (p = 0.028). Conclusion: Sialendoscopy is an effective treatment option for the management of RAIS and xerostomia refractory to conservative therapy and medical management. Patients in our cohort report durable improvement in symptoms after intervention.

Research paper thumbnail of Outcomes of Pediatric Patients with Malignancies of the Major Salivary Glands

Annals of Surgical Oncology, Jun 29, 2010

Background.-To report the outcomes and early to long term treatment complications among pediatric... more Background.-To report the outcomes and early to long term treatment complications among pediatric patients with major salivary gland malignancies treated at a single institution. Materials and Method.-This study was a retrospective case review set at a tertiary referral cancer center. Patients less than 19 years of age with a diagnosis of a major salivary gland malignancy were identified at the M. D. Anderson tumor database between 1953 and 2006. Results.-A total of 61 patients were identified, with equal gender distribution. The majority of tumors arose in the parotid gland (83%), and the most common pathology was mucoepidermoid carcinoma (46%). Lymphatic metastasis was identified in 37% of patients, nearly all with mucoepidermoid carcinoma. Although 65% of patients had prior treatment elsewhere, more than 75% of patients underwent surgical resection at our institution. External beam radiation was used in 45% of patients, with an average dose of 58.6 Gray. Average patient follow-up was 153 months. The overall survival rate was 93% at 5 years, and 26% developed a recurrence. A second primary was identified in 2 patients. Permanent facial paresis was noted in 7 patients (12%) and xerostomia in 1 patient (4%). Conclusions.-Survival of pediatric patients with major salivary gland carcinomas is favorable. Adverse outcomes were best predicted by tumor grade, margin status, and neural involvement. Radiation therapy is beneficial for locoregional control of disease, with acceptable long-term FIGURE 1.-a Distribution of pediatric major salivary gland tumors by histology. (Reprinted from Kupferman ME, de la Garza GO, Santillan AA, et al. Outcomes of pediatric patients with malignancies of the major salivary glands. Ann Surg Oncol. 2010;[Epub ahead of print], with kind permission from Springer Science+Business Media: Annals of Surgical Oncology.

Research paper thumbnail of Genetic and Expression Analysis of HER-2 and EGFR Genes in Salivary Duct Carcinoma: Empirical and Therapeutic Significance

Clinical Cancer Research, Apr 14, 2010

Purpose: Salivary duct carcinoma overexpresses epidermal growth factor receptor (EGFR) and HER-2,... more Purpose: Salivary duct carcinoma overexpresses epidermal growth factor receptor (EGFR) and HER-2, although the underlying mechanisms remain undefined. Because of the potential utilization of these markers as treatment targets, we evaluated protein and gene status by several techniques to determine complementary value. Experimental Design: A tissue microarray of 66 salivary duct carcinomas was used for immunohistochemical analysis of HER-2 and EGFR expression (semiquantitatively evaluated into a three-tiered system), and fluorescence in situ hybridization for gene copy number, and chromosomes 7 and 17 ploidy status. Sequencing of exons 18, 19, and 21 of the EGFR gene for mutations was carried out. Result: For EGFR, 46 (69.7%) of the 66 tumors showed some form of EGFR expression (17 at 3+, 17 at 2+, 12 at 1+) but none gene amplification. Five (9.4%) of 53 tumors showed mutations in exon 18 (n = 3) and exon 19 (n = 2). Polysomy of chromosome 7 (average >2.5 copies/cell) was detected in 15 (25.0%) of 60 tumors (6 at 3+, 5 at 2+, 2 at 1+, 2 at 0+ expression) and correlated with poor 3-year survival (P = 0.015). For HER-2, 17 (25.8%) of 66 tumors expressed HER-2 (10 at 3+, 3 at 2+, 4 at 1+). Eight tumors showed HER-2 gene amplification (6 at 3+, 1 at 1+, 1 at 0+ protein expression). Chromosome 17 polysomy was found in 8 (15.7%) of 51 tumors; two had HER-2 expression (3+, 1+). Conclusion: Our study shows that salivary duct carcinomas (a) harbor EGFR gene mutations in a subset of tumors that may guide therapy, (b) pursue an aggressive clinical course in cases with chromosome 7 polysomy and high EGFR expression, and (c) with HER-2 gene amplification and protein high expression, may be selected for targeted therapy. Clin Cancer Res; 16(8); 2266-74. ©2010 AACR.

Research paper thumbnail of The role of postoperative adjuvant radiation therapy in the treatment of mucosal melanomas of the head and neck region

Archives of Otolaryngology-head & Neck Surgery, Aug 1, 2003

Research paper thumbnail of Differential Expression of Hormonal and Growth Factor Receptors in Salivary Duct Carcinomas

The American Journal of Surgical Pathology, Nov 1, 2007

Research paper thumbnail of Presence of malignant tumor cells in persistent neck disease after radiotherapy for advanced squamous cell carcinoma of the oropharynx is associated with poor survival

European Archives of Oto-rhino-laryngology, Nov 22, 2005

Non-surgical therapy consisting of external beam radiation with or without chemotherapy is an eff... more Non-surgical therapy consisting of external beam radiation with or without chemotherapy is an effective treatment for patients with squamous cell carcinoma (SCC) of the oropharynx with advanced neck disease (N2a or greater). However, many of these patients have to undergo a neck dissection for clinically persistent regional disease. It is reported that nearly 50% of the neck dissection specimens contain residual viable tumor cells that may indicate partial radiation failure and as a consequence poor survival. In order to address the significance of this finding, we conducted a nonrandomized retrospective study, including 35 patients who underwent definitive radiation therapy followed by either a radical or modified radical (RND/MRND) or a selective neck dissection (SND) for clinically persistent neck disease 6 weeks after completing therapy for stage III/IV SCC of the oropharynx (base of the tongue =15, tonsil =12, soft palate =7 and pharyngeal wall =1). All neck dissection specimens were reviewed according to histological criteria indicating viable residual tumor. We observed an increased relative risk (RR) for local and regional failures in the patient population with viable cancer cells in the post-irradiation neck specimens (RR=6.7 and 4.1, respectively). The presence of malignant tumor cells in residual disease in the neck correlated with poor disease-specific and overall survival (P =0.03 and P =0.01, respectively). Of note, the extent of neck dissection did not improve the disease-free or overall survival in this patient population (P =0.5 and P =0.6, respectively). In conclusion, the presence of viable cancer cells in radiated neck nodes is a novel prognostic marker for disease-specific survival in patients treated for SCCs of the oropharynx with advanced neck disease and may serve as an identifier for patients who will benefit from post-treatment chemoprevention.

Research paper thumbnail of Molecular and Clinicopathologic Comparisons of Head and Neck Squamous Carcinoma Variants

The American Journal of Surgical Pathology, Oct 1, 2004

To investigate, for the first time, the events associated with the phenotypic and clinical divers... more To investigate, for the first time, the events associated with the phenotypic and clinical diversities of head and neck squamous carcinomas (HNSC), we performed molecular analyses on 92 primary tumors representing the entire spectrum of the morphologic subtypes using microsatellite markers at chromosome 3p, 4p, 8p, 9p, 11q, 17p, and 18q regions and correlated the results with the clinicopathologic features and patients' survival. Loss of heterozygosity (LOH) at D9S168 and D9S171 markers on chromosome 9p regions was commonly identified in all subtypes. Distinctive alterations in certain subtypes were noted at chromosomes 3p, 4p, 8p, and 11p regions. In general, less aggressive types (verrucous, papillary, and well-differentiated conventional) had a significantly lower LOH incidence than the more aggressive (basaloid, sarcomatoid, and highgrade conventional squamous carcinoma) categories. Significant association between LOH and age, stage, nodal status, and patient outcome was found. Survival analysis revealed that pathologic categorization (less versus more aggressive) and LOH at marker D11S4167 and D3S2432 are independent predictors of patients' survival. Our analysis also defined a set of limited markers that account for most of alterations within and across these tumor subtypes. Our study indicates that 1) certain genetic markers are common to all subtypes of HNSC supporting their early involvement in tumorigenesis, 2) inter-and intratumoral genetic differences evolve subsequently and may underlie their morphologic heterogeneity, 3) high incidence of LOH in certain regions characterizes aggressive tumors, 4) categorical classification and LOH at 11p and 3p regions independently correlated with patient survival, and 5) a limited set of markers identify the majority of genetic alterations in these tumors.

Research paper thumbnail of Moderately Differentiated Neuroendocrine Carcinoma (Atypical Carcinoid) of the Larynx: A Clinically Aggressive Tumor

Laryngoscope, Jul 1, 2005

To evaluate the presentation, treatment, and outcome of a small series of patients with moderatel... more To evaluate the presentation, treatment, and outcome of a small series of patients with moderately differentiated neuroendocrine carcinoma (MDNC) of the larynx seen at one institution and to provide information on this uncommon laryngeal malignancy for therapeutic decision making. Retrospective analysis of medical records. Cases were identified from databases maintained by the medical informatics and pathology departments. Patient, tumor, treatment, and outcome data were collected from medical records. Main outcome measures were recurrence, overall and disease-specific survival, and cause of death. Eleven patients (6 males; 5 females) seen between 1990 and 2003 had sufficient documentation for further evaluation. Patients presented with dysphagia, throat pain, or hoarseness, and all tumors arose in the supraglottis. Eight of 11 patients gave a history of cigarette use. Of the 10 patients treated with curative intent, 7 who recurred all died with disease. The average disease-free interval was 54 months, with a range of 2 to 101 months. The overall and disease-specific survival was 64 and 54 months, respectively. Nine patients were alive 3 years after diagnosis. No correlations with age, stage at presentation, or initial treatment modality and outcome (recurrence or survival) were found. Laryngeal MDNC is an aggressive malignancy with frequent regional and distant metastases. Although surgical resection is usually recommended, patients did respond to radiation and chemotherapy, suggesting a combined approach may be indicated. Aggressive initial therapy is needed because development of recurrence portends a poor outcome.