Carcinoma in situ Research Papers (original) (raw)

Modulation of cellular antigens in chronically infected CEM cells by HTLV-IIIB. 0-propiolactone-treated cells were acetone-fixed and stained with monoclonal antibodies; hence membrane and cytoplasmic antigen is detected. Filled columns, infected; hatched columns, uninfected cells. Similar results were obtained by flow cytometnc analysis of intact cells. in pathogenicity among virus variants between and within HIVinfected individuals and AIDS patients.4

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- Breast Cancer, Menopause, Follow-up studies, Mastectomy
- by Claudio Botti
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- Breast Cancer, Adolescent, Cytoskeleton Regulation, Cytoskeleton

Background Breast cancer is the most frequently diagnosed cancer in women. Intraepithelial lesions (IELs), such as usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors that predict a woman's chance of developing invasive breast cancer. Therefore, a comparative study that establishes an animal model of pre-invasive lesions is needed for the development of preventative measures and effective treatment for both mammary IELs and tumors. The purpose of this study was to characterize the histologic and molecular features of feline mammary IELs and compare them with those in women. Methods Formalin-fixed, paraffin-embedded specimens (n = 205) from 203 female cats with clinical mammary disease were retrieved from the archives of the Purdue University Animal Disease Diagnostic Laboratory and Veterinary Teaching Hospital (West Lafayette, IN), and the Department of Pathology and Veterinary Clinic, School of Veterinary Medici...

- by Sulma Mohammed
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- Veterinary Medicine, Breast Cancer, Immunohistochemistry, Comparative Study

The gluteal-fold flap was used to reconstruct vulvar and posterior vaginal wall defects in 40 patients. This is a fasciocutaneous, islanded flap based on the internal pudendal artery and vein perforators. The flap is robust and has the advantage of being away from the pathway of carcinoma spread. In addition it has minimal donorsite morbidity as the scar is hidden in a natural crease.

- by R. Ragoowansi
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- Long Term Care, Treatment Outcome, Medicine, Follow-up studies

The terminology for human papillomavirus (HPV)–associated squamous lesions of the lower anogenital tract has a long history marked by disparate diagnostic terms derived from multiple specialties. It often does not reflect current knowledge of HPV biology and pathogenesis. A consensus process was convened to recommend terminology unified across lower anogenital sites. The goal was to create a histopathologic nomenclature system that reflects current knowledge of HPV biology, optimally uses available biomarkers, and facilitates clear communication across different medical specialties. The Lower Anogenital Squamous Terminology (LAST) Project was cosponsored by the College of American Pathologists and the American Society for Colposcopy and Cervical Pathology and included 5 working groups; 3 work groups performed comprehensive literature reviews and developed draft recommendations. Another work group provided the historical background and the fifth will continue to foster implementation...

- by Ritu Nayar
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- Clinical Pathology, Colposcopy, Clinical Sciences, Precancerous Conditions

The aim of our study was to evaluate the therapeutic effectiveness of loop electrosurgical excision procedure (LEEP) in Greek patients with vulvar intraepithelial neoplasia (VIN). Between January 2002 and January 2009, 55 women with histologically confirmed VIN usual type were included in our study. For the LEEP procedure we used a high frequency electrosurgical unit with at least 80 W output. The tissue was removed to the second surgical plane. Statistical analyses were performed using the SPSS-13 for Windows. Complete response rate at 12-month follow-up was 100%. Complete response rate at 48 months of follow-up was 80%. Recurrence rate at 48 months of follow-up was 20%. LEEP may constitute a valuable excisional method for the treatment of VIN. It provides an interpretable specimen of the whole lesion within a few minutes. It needs a short period of training and has low cost.

- by Dimitrios Zygouris
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- Treatment Outcome, Greece, Hysterectomy, European
- by Damien Bolton
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- Australia, Clinical Sciences, Standard of Care, BCG vaccine
- by Sulma Mohammed
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- Veterinary Pathology, Nonparametric Statistics, Biology, Immunohistochemistry

The prevalence of prostatic intraepithelial neoplasia (PIN) in men who underwent surgery for benign prostatic hyperplasia (BPH) before and after the Chernobyl nuclear accident was studied. BPH samples were obtained by adenomectomy from 45 patients operated in 1984 before the accident (Group I), and 47 patients from the low contaminated Kiev City (Group II) and 76 from high contaminated area (Group III) operated between 1996 and 1998. Their BPH samples were examined histologically and immunohistochemically. The incidences of prostatic intraepithelial neoplasia (PIN) and high grade PIN (HGPIN) were 15.5 and 11.1% in Group I, 29.8 and 14.9% in Grpoup II, and 35. 5 and 19.7% in Group III. The difference between the incidences of PIN in Group I and III is significant (p<0.02). There was increased apoptosis in areas of PIN in Group II and III as compared to Group I (p<0.001). Since apoptosis has been shown to be associated with ionizing radiation and it is now found to be associated...

- by Gabriel Haas
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- Prostate Cancer, Apoptosis, Environmental Pollution, Medicine
- by Mattia Intra
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- Biology, Survival Analysis, Treatment Outcome, Medicine

Bowen's disease (cutaneous squamous cell carcinoma in situ), like other cancers of the skin, is rare in black peopleto our knowledge, only about 43 cases have been published in the medical literature. We report a 59-year old... more

- by Abdullahi MOHAMMED
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- Medicine, Thorax, Pruritus, Skin Neoplasms
- by David Gaucher
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- Optometry and Ophthalmology, Corneal Opacity, Carcinoma in situ
- by Marie-france Poupon
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- Neoplasm Invasiveness, Carcinoma in situ, Neoplasm metastasis

Normal Gonadal Development Phenotypic sexual differentiation is the result of 3 consecutive processes: stabilization and development of the primitive urogenital ridge, differentiation of the bipotential gonad into either a testis or an ovary, referred to as (gonadal) sex determination, and finally intact hormone production and action by the differentiated gonad [Grumbach et al., 2003] (fig. 1). In the last decades, several genes have been identified mostly in mice that are involved in this process at one or more levels. Steroidogenic factor 1 (Sf1, encoded by Nr5a1), Wt1 (Wilms' tumor 1), Lhx9 (LIM homeobox protein 9), and Emx2 (empty spiracles homolog 2) are important for stabilization and development of the urogenital ridge [Wilhelm and Koopman, 2006; Wilhelm et al., 2007a; Lin and Achermann, 2008]. At this stage, a balanced antagonism of male (Sox9 , SRYbox containing gene 9) and female (Rspo1 , R-spondin homolog) opposing signals, at very low expression levels, has been proposed to keep the gonad in a bipotential stage [Schlessinger et al., 2010]. In males, testis development is initiated around 10.5 days post coitum (dpc) by Sry (sexdetermining region of chromosome Y) expression from the Y chromosome [Koopman et al., 1991]. However, at present, Sox9 rather than Sry is considered to be the

- by Stenvert Drop
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- Adolescent, Biological Sciences, Child, Disorders of sex development

were operated with LRN safely, although there are more challenging procedures. We reported our experience managing renal masses ≥10 cm with transperitoneal LRN and compared this technique versus open radical nephrectomy (ORN) in terms of duration of hospitalization, complications, operative and perioperative outcomes. Materials and Methods: A retrospective analysis was performed in 114 patients (ORN=65; LRN n=49) that underwent surgery for kidney tumors from 2007 until 2012. Patients with T1 and T4 tumors (tm) were excluded from the study. The transperitoneal approach was preferred in all patients who underwent LRN. Patients' age, tumor size, preoperative surgical risk score, duration of hospitalization, complications and hospitalizations' costs were recorded. The complications (cp) in both groups were specified with the Modified Clavien System in five grades. Chi square test was used to assess differences in the response between the two groups and the Fisher's test, if necessary. All p-values less than 0.05 were considered statistically significant. Results: The mean age was found 56.34±14.54 years in the ORN group (G) and 57.18±13.41 years in the LRN G (p=0.247). Tumor size was calculated 9.52±2.36 (7-16) cm in the ORN G and 9.72±1.73 (7-15) cm in the LRN G (p=0.495). In the ORN G, T2 tm were found in 51 (78.4%) patients and T3 tm in 14 (21.5%) patients. In the LRN G, T2 tm were identified in 37 (75.5%) patients and T3 tm in 12 (24.5%) patients (p=0.362). There was no significant difference between the two groups in terms of mean age, American Society of Anesthesiologists (ASA) score, mean tumor size and tumor stages. After an early post-operative period pain necessitating analgesics was observed in all patients (100%) of both groups (Grade 1 cp). Blood transfusion was required in 19 patients (29.2%) in the ORN G and 11 (22.4%) patients in the LRN G (Grade 2 cp) (p=0.560). Grade 3 cp was not observed in either group. Grade 4 cp occurred in 4 (6.1%) patients (acute tubular necrosis (2), the need for dialysis, pulmonary embolism, atrial fibrillation) in the ORN G and in 1 (2%) patient (atrial fibrillation) in the LRN G. Grade 5 cp did not occur in either group. The mean hospital stay was 4.95±1.85 days in th eORN G and 3.10±1.67 days in the LRN G (p<0.001). The mean follow-up period was calculated 39 months for the ORN G and 32 months for the LRN G. Local recurrence occurred in 2 (3%) patients in the ORN G. Two patients in ORN G and 2 patients in LRN G died during the follow-up period. Discussion and Conclusion: The most controversial topic in literature concerns the risk of local recurrence in patients with T2 or T3 tm that underwent LRN, although the incidence of disease recurrence seems to be more prominent in patients with high-grade tm (2). Therefore, LRN can be safe in terms of duration of hospitalization, complications, operative and perioperative outcomes by experienced laparoscopists for very large renal masses (≥10 cm). In our study blood transfusion and complication rates are higher for ORN in pT2/T3 patients and unrelated to tumor and total specimen size.

- by Luigi Silvestri
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- Urology, Urinary incontinence, Urodynamics, Cystectomy

Mammary intraepithelial lesions (IELs) are noninvasive epithelial proliferations that include ductal hyperplasia (DH), atypical DH (ADH), and ductal carcinoma in situ (DCIS). In women, IELs are associated with increased risk of invasive breast cancer and form a basis for therapeutic decisions. Similarly, in female dogs, IELs are common in tumor-bearing glands and in non-tumor-bearing glands. To determine the prevalence and types of spontaneous IELs, mammary glands from 108 female dogs without clinical mammary disease were evaluated histologically and immunohistochemically. Within this population, 56 dogs (52%) had at least one type of spontaneous IEL, including DH (49 dogs), ADH (14 dogs), low-grade DCIS (19 dogs), intermediate-grade DCIS (12 dogs), and high-grade DCIS (1 dog). Twenty-one dogs had two or more different IEL types. In 23 of 24 dogs with atypical IELs (ADH or DCIS), immunohistochemical expression was determined for estrogen receptor α (ER-α), progesterone receptor (PR)...

- by Sulma Mohammed
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- Veterinary Pathology, Nonparametric Statistics, Biology, Immunohistochemistry
- by Julie Schnur
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- Biopsy, Clinical oncology, Breast Neoplasms, Carcinoma in situ
- by José Fonseca-Moutinho
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- Carcinoma in situ

Breast microcalcifications are key diagnostically significant radiological features for localisation of malignancy. This study explores the hypothesis that breast calcification composition is directly related to the local tissue pathological state. A total of 236 human breast calcifications from 110 patients were analysed by mid-Fouries transform infrared (FTIR) spectroscopy from three different pathology types (112 invasive carcinoma (IC), 64 in-situ carcinomas and 60 benign). The biochemical composition and the incorporation of carbonate into the hydroxyapatite lattice of the microcalcifications were studied by infrared microspectroscopy. This allowed the spectrally identified composition to be directly correlated with the histopathology grading of the surrounding tissue. The carbonate content of breast microcalcifications was shown to significantly decrease when progressing from benign to malignant disease. In this study, we report significant correlations (P<0.001) between mi...

- by Nicholas Stone
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- Carbonates, Carcinoma, Calcinosis, Breast Neoplasms

The CDKN2A gene locus encodes two different proteins derived from alternative splicing. p16 (exons 1␣, 2, and 3) acts as a G 1 cell cycle regulator, and p14 ARF (exons 1␤, 2, and 3) acts to modulate MDM2mediated degradation of p53. Inactivation of p16 is a common finding in many cancers; however, there is little data on CDKN2A gene abnormalities in oral precancer. In this longitudinal study, we examined changes in the CDKN2A gene locus in sequential epithelial dysplasias and oral carcinomas from 11 patients. Genomic DNA was extracted from laser-microdissected lesional tissue, and exons 1␣, 1␤, and 2 were analyzed by duplex PCR. Immunohistochemistry was done to identify p16 and p14 ARF protein expression. Two adjacent polymorphic microsatellite markers were used for allelotyping. Homozygous deletion of exon 1␣ was identified in 2 of 17 (12%) precancerous lesions. Loss of either exon 1␣, exon 2, or both was seen in seven of nine (78%) carcinomas. In five of these carcinomas, there was loss of only exon 1␣. No case showed deletion of exon 1␤. In 5 of 11 patients, microsatellite markers showed differing patterns of allelic imbalance in the precancerous lesions and the subsequent carcinoma, suggesting a complex genetic pattern of progression from dysplasia to carcinoma. We conclude that during oral carcinogenesis homozygous deletion of exon 1␣ of the CDKN2A gene is common but that deletion of exon 2 and 1␤ is less frequent. Moreover, our results suggest that the progression from oral precancer to cancer, in some cases, is more complex genetically than predicted by linear models of carcinogenesis.

- by NALIN THAKKER
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- Genetics, Cancer, Cell Cycle, Immunohistochemistry

The intraductal approach is particularly appeal-ing in the setting of ductal carcinoma in situ (DCIS), a preinvasive breast neoplasm that is thought to be entirely intraductal in its extent. Based on an emerging understand-ing of the... more

- by shelley hwang
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- Oncology, Breast Cancer, Medicine, Molecular Diagnostics

Association of breast carcinoma and multiple intraductal papillomas: an histological and immunohistochemical investigation To identify histological preneoplastic lesions and early neoplastic foci, a histological and immunohistochemical study has been conducted on a series of 18 cases with the rare association of multiple intraductal papillomas and in situ breast carcinoma. The pathological and clinical data of these cases have been collated. A close anatomical and spatial association between the benign papillomas and areas of in situ carcinoma (mostly of the cribriforrn type) was a frequent finding. In agreement with the results of our previous investigations, cytoplasmic CEA has been found to be a marker of intraductal carcinomas, while staining for actin has been found useful to identify the myoepithelial cells present in benign papillomas as opposed to carcinomas. The immunohistochernical procedures for these two markers have been conducted on parallel sections; alternatively, an immunoperoxidaselimmuno-galactosidase sequence has been applied on the same section. The results indicate that, in cases with multiple papillomas, CEA-positive, myoepitheiial cell-free carcinomatous areas can be anatomically associated with and even present inside the benign-looking papillary lesions. These findings can be interpreted as evidence of a malignant transformation of intraductal papillomas, or, less likely, of their 'cancerization' by ductal carcinoma.

- by Gianni Bussolati
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- Immunohistochemistry, Histopathology, Actin, Clinical Sciences

The objective of the study was to evaluate the risk of anal squamous intraepithelial lesions (ASILs) in immunocompetent women with genital squamous intraepithelial lesions (GSILs). STUDY DESIGN: This was a cross-sectional study that included 260 immunocompetent women divided into 2 study groups: 1 group included 184 women diagnosed with GSIL by genital colposcopy and biopsy, and the other included 76 controls. All subjects were submitted to anoscopy followed by a biopsy if pertinent. RESULTS: Of 184 GSIL women, 32 (17.4%) had ASIL (P Ͻ .001). The risk of ASIL was 13.1 times greater for GSIL women when there were 3 or 4 genital sites involved. All cases of high-grade ASIL were found in women with cervical GSILs. Among risk factors, anal intercourse without a condom demonstrated an important association with ASIL (prevalence ratio adjusted for age ϭ 2.6). CONCLUSION: There seems to be a strong association between ASIL and multicentric GSIL. Another factor related to ASIL was the practice of unprotected anal intercourse.

- by José Eleutério
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- Brazil, Adolescent, Comorbidity, Multivariate Analysis

Summary. Objectives. To evaluate quality of life and voice in patients previously treated for early laryngeal cancer versus healthy controls and to assess correlations between demographic and cancer characteristics and posttreatment... more

- by Saulius Vaitkus
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- Depression, Quality of life, Endoscopy, Anxiety
- by Munechika Misumi
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- Radiation, Risk, Japan, Biological Sciences

Contributors C. Paul conceptualized the idea, in discussion with B. Brookes; reviewed the literature; and wrote the first draft of the article. B. Brookes revised the article for important intellectual content.

- by charlotte paul
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- Sociology, Human Rights, Prejudice, Medicine
- by ERCAN ARCA
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- Management, Dermatology, Medicine, Melanoma

UNLABELLED Frozen section examination is aimed at making a preoperative diagnosis, determining the benign or malignant nature of a breast lesion, but also the most suitable surgical procedure. The sensitivity and specificity of this method and the causes of discrepancies were analyzed in a retrospective study of 2 177 breast lesions. METHOD 1,150 frozen sections from 2,177 breast lesions were performed in the interval 1999-2005. The sections made at the open door cryostat and measuring 5 microm were stained with rapid Hematoxylin-Eosin. The following terms were used for describing the intraoperative diagnosis: negative, positive, and await paraffin section. After the frozen section diagnosis was made, the frozen tissue was thawed to room temperature and fixed in formalin overnight for further paraffin processing. The remaining unfrozen tissue was processed into a paraffin section. RESULTS The number of cases and the number of frozen sections increased from 1999 (341 cases, 87 frozen...

- by Dana Dobru
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- Medicine, Neoplasm Invasiveness, Retrospective Studies, Intraoperative Period

Around 70% of bladder tumors are non muscle-invasive at diagnosis and of these, 70% are stage Ta, 20% are stage T1, and 10% are carcinoma in situ (CIS). Bladder cancer is staged according to the 2002 tumor, nodes, metastases (TNM) classification approved by the Union International Contre le Cancer (Table 1.1). In this classification, papillary tumors confined to the urothelium

- by John Kelly
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- Bladder Cancer, Basement Membrane, Carcinoma in situ
- by Raj Persad
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- Medicine, Bladder Cancer, Cancer Therapy, Postgraduate medical education
- by C. Speeg-schatz
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- Optometry and Ophthalmology, Corneal Opacity, Carcinoma in situ

HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires

One hundred fifty-six consecutive cases of carcinoma of the anal canal and margin diagnosed between 1959 and 1986 were reviewed. There were 27 cases between 1959 and 1967, 41 between 1968 and 1976, and 88 between 1977 and 1986. Although the female-to-male ratio remained constant at 1.5:1, a high-risk group emerged, consisting of male patients with admitted homosexuality, bisexuality, or a history of anal condylomata acuminata. During the earliest period, 8 percent of male patients were in this group; this subset rose to 72 percent during the latest period (P < .05). While the number of anal margin cancers has decreased, there has been a steady rise in the number of anal canal and in situ carcinomas, especially in the high-risk group.

- by Steven Wexner
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- Homosexuality, Squamous Cell Carcinoma, Risk factors, Clinical Sciences

Considerable progress has been made in understanding breast lesions utilizing molecular methods, but conventional morphology, simple immunohistochemical stains and common sense still prevail in diagnosing the vast majority of breast disease. The focus of this review is to identify the most common breast lesions sent to our consultation practice, and to reiterate salient diagnostic features, differential diagnoses and common pitfalls in identifying these lesions. Separation of epithelial proliferative lesions and differentiation between usual epithelial hyperplasia (UEH) and atypical ductal hyperplasia (ADH) are the most common problems encountered in our Consultation practice. Differentiation between UEH and ADH is based on the assumption that ADH is a clonal process, recognized by a uniform phenotype and more recently described immunohistochemical markers such as differential cytokeratin and also hormone receptor expression. Difficulty in subtyping invasive carcinomas and exclusion of in situ and ⁄ or invasive carcinoma in a sclerosing lesion is also commonly noted. Finally, problems in distinguishing various papillary and fibroepithelial lesions are also encountered. The use of common immunohistochemical stains such as various cytokeratin and myoepithelial markers, E-cadherin and hormone receptors is helpful in solving most of these diagnostic dilemmas.

- by Sarah Pinder
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- Histopathology, Differential Diagnosis, Fibrosis, Hyperplasia

Blinded urinary assays for cyclic guanosine 3':5'-monophos- phate (cGMP) and cyclic adenosine 3':5'-monophosphate (cAMP) were performed on 49 subjects with documented ab normal cervical cytology and 21 control subjects with normal cytology. A significant difference in the mean cGMP:cAMP ratios between the case and control groups was found. A significantly greater proportion of women with cytological ab normalities had a

- by Chandralekha Duttagupta
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- Cancer, cyclic AMP, Cyclic nucleotides, Indexation

Recombinant vaccinia virus has been widely employed as a cancer vaccine in several clinical trials. In this study we explored, employing BALB/c mice transgenic for the rat neu oncogene, the ability of the recombinant vaccinia virus neu (rV-neuT) vaccine to inhibit growth of neu+ mammary carcinomas and whether the efficacy of vaccination was dependent on: a) carcinogenesis stage at which the vaccination was initiated; b) number of vaccinations and c) route of delivery (systemic vs local). BALB-neuT mice were vaccinated one, two and three times by subcutaneous (s.c) and intramammary gland (im.g) injection with rV-neuT or V-wt (wild type vaccinia virus) starting at the stage in which mouse mammary gland displays atypical hyperplasia, carcinoma in situ or invasive carcinoma. We demonstrated that vaccination using rV-neuT was more effective when started at an earlier stage of mammary carcinogenesis and after three vaccinations. im.g vaccination was more effective than s.c vaccination in inhibiting mammary carcinogenesis, eliciting anti-Neu antibodies, increasing anti-Neu IgG2a/G3 isotypes and inducing antibodies able to trigger mammary tumor cell apoptosis and antibody dependent cellular cytotoxicity. The better protective ability of rV-neuT im.g vaccination was associated with its capacity to induce a superior degree of in vivo mammary cancer cell apoptosis. Our research suggests that intratumoral vaccination using recombinant vaccinia virus could be employed to increase the activity of a genetic cancer vaccine. This study may have important implications for the design of cancer vaccine protocols for the treatment of breast cancer and of accessible tumors using recombinant vaccinia virus.

- by Roberto Bei
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- Genetics, Immunology, Clinical Trial, Breast Cancer

Purpose: We assessed the ability of laser induced autofluorescence to differentiate malignant from nonmalignant bladder lesions. Materials and Methods: We studied 53 patients with bladder cancer undergoing mucosal biopsies or transurethral resection of a bladder tumor. A quartz optical fiber was advanced through the working channel of a cystoscope and placed in gentle contact with the bladder. Tissue fluorescence was excited by 337 nm. light pulses (nitrogen laser). One fiber was used for transmission of the excitation and emission (fluorescence) light. An optical multichannel analyzer system was used to record fluorescence spectra of the sites of interest. Results: We analyzed the fluorescence spectra of 114 bladder areas (1 carcinoma in situ as well as 28 malignant, 35 inflammatory, 7 dysplastic, 1 squamous metaplastic and 42 normal areas). These lesions included 44 difficult to diagnose suspicious tumors (11 malignant and 33 nonmalignant). We developed an algorithm that used the 1385:1455 nm. fluorescence ratio to distinguish malignant from nonmalignant lesions, including inflammatory areas. By analyzing the data on all 114 lesions, we noted the sensitivity, specificity, and positive and negative predictive values of this method for differentiating malignant from nonmalignant bladder lesions to be 97,98,93 and 99%, respectively. Conclusions: Under excitation with 337 nm. light a clear differentiation between malignant and nonmalignant bladder tissues can be made using the 13851455 nm. autofluorescence ratio.

- by Sigrid Avrillier
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- Algorithms, Urology, Bladder Cancer, Lasers

- by Antonio Carbone
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- Urology, Medicine, Urinary incontinence, Urodynamics

Background: Non-attendance at gynecological clinics is a major limitation of cervical cancer screening and self-collection of samples may improve this situation. Although HPV testing of self-collected vaginal samples is acceptable, the specificity is inadequate. The current focus is increasing self-collection of vaginal samples to minimize clinic visits. In this study, we analyzed the concordance and clinical performance of DNA methylation biomarker (PAX1, SOX1, and ZNF582) detection in self-collected vaginal samples and physician-collected cervical samples for the identification of cervical neoplasm. Methods: We enrolled 136 cases with paired methylation data identified from abnormal Pap smears (n = 126) and normal controls (n = 10) regardless of HPV status at gynecological clinics. The study group comprised 37 cervical intraepithelial neoplasm I (CIN1), 23 cervical intraepithelial neoplasm II (CIN2), 16 cervical intraepithelial neoplasm III (CIN3), 30 carcinoma in situ (CIS), 13 squamous cell carcinomas (SCCs) and seven adenocarcinomas (ACs)/adenosquamous carcinomas (ASCs). PAX1, SOX1 and ZNF582 methylation in study samples was assessed by real-time quantitative methylation-specific polymerase chain reaction analysis. We generated methylation index cutoff values for the detection of CIN3+ in physician-collected cervical samples for analysis of the self-collected group. Concordance between the physician-collected and self-collected groups was evaluated by Cohen's Kappa. Sensitivity, specificity and area under curve (AUC) were calculated for detection of CIN3+ lesions. Finally, we produced an optimal cutoff value with the best sensitivity from the self-collected groups. Results: We generated a methylation index cutoff value from physician-collected samples for detection of CIN3+. There were no significant differences in sensitivity, specificity of PAX1, SOX1 and ZNF582 between the self-collected and physician-collected groups. The methylation status of all three genes in the normal control samples, and the CIN 1, CIN2, CIN3, CIS, ACs/ASCs and SCC samples showed reasonable to good concordance between the two groups (κ = 0.443, 0.427, and 0.609 for PAX1, SOX1, and ZNF582, respectively). In determining the optimal cutoff values from the self-collected group, ZNF582 showed the highest sensitivity (0.77; 95%CI, 0.65-0.87) using a cutoff value of 0.0204. Conclusions: Methylation biomarker analysis of the three genes for detection of CIN3+ lesions shows reasonable to good concordance between the self-collected and physician-collected samples. Therefore, self-collection of samples could be adopted to decrease non-attendance and improve cervical screening.

- by Yaw-wen Hsu
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- Epigenomics, Polymerase Chain Reaction, DNA methylation, ROC Curve

With the development of expertise in image guidance for breast surgery, many surgeons now perform preoperative wire localization themselves. Use of a single wire versus multiple wires to bracket a radiographic breast abnormality has previously been described, although benefits of this technique based on clinical outcomes such as margin status, tissue volume removed, and re-excision rates have not been established. This study is a retrospective analysis of wire-localized breast biopsies performed by 14 surgeons over 29 months; stereotactic and ultrasound guidance were used. During this time, 489 wire localizations were done, of which 159 used multiple wires. Two hundred eleven of these biopsies were done for malignant disease, 86 using multiple wires. After controlling for tumor node metastases stage, single and multiple wire placements were compared using endpoints of margin status, need for re-excision, and total volume of tissue removed. Neither margin status nor re-excision was r...

- by Michael Biderman
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- Surgery, Treatment, Localization, Treatment Outcome

It has been reported that the diagnosis of serous tubal intraepithelial carcinoma (STIC) is not optimally reproducible based only on histologic assessment. Recently, we reported that the use of a diagnostic algorithm that combines histologic features and coordinate immunohistochemical expression of p53 and Ki-67 substantially improves reproducibility of the diagnosis. The goal of the current study was to validate this algorithm by testing a group of 6 gynecologic pathologists who had not participated in the development of the algorithm (3 faculty, 3 fellows) but who were trained in its use by referring to a website designed for that purpose. They then reviewed a set of microscopic slides, which contained 41 mucosal lesions of the fallopian tube. Overall consensus (≥4 of 6 pathologists) for the 4 categories of STIC, serous tubal intraepithelial lesion (our atypical intermediate category), p53 signature, and normal/reactive was achieved in 76% of lesions with no consensus in 24%. Combining diagnoses into 2 categories (STIC vs. non-STIC) resulted in overall consensus in 93% with no consensus in 7%. The kappa value for STIC vs. non-STIC among all 6 observers was also high at 0.67 and did not significantly differ whether for faculty (κ=0.66) or fellows (κ=0.60). These findings confirm the reproducibility of this algorithm by a group of gynecologic pathologists who were trained on a website for that purpose. Accordingly, we recommend its use in research studies. Before applying it in routine clinical practice, the algorithm should be evaluated by general surgical pathologists in the community setting.

- by Jeffrey Seidman
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- Algorithms, Observer Variation, Reproducibility of Results, Carcinoma in situ

Pancreatic ductal adenocarcinoma (PDAC) is the most common pancreatic malignancy with a dismal prognosis. Developing novel strategies to prevent or delay pancreatic cancer is currently of intense interest. The chemopreventive efficacy of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, was evaluated against the progression of pancreatic intraepithelial neoplasms (PanIN) to PDAC in conditional LSL-Kras G12D/+ transgenic mice. LSL-Kras G12D/+ and p48 Cre/+ mice were bred, and offspring of activated Kras G12D/+ were generated. Six-week-old male Kras G12D/+ (20 per group) and C57BL/6 wild-type (12 per group) mice were fed (AIN-76A) diets containing 0, 100, and 200 ppm of gefitinib for 35 weeks. At termination, pancreases were evaluated histopathologically for PanINs and PDAC, and various biomarkers were measured by immunohistochemistry, immunofluorescence, immunoblotting, and/or reverse transcription-PCR. Dietary gefitinib at 100 and 200 ppm significantly suppressed PDAC incidence by 77% and 100%, respectively (P < 0.0001) when compared with control diet. Importantly, a significant inhibition of carcinoma and a dose-dependent suppression of PanINs [PanIN-1, 37-62% (P < 0.002); PanIN-2, 38-41 (P < 0.001); and PanIN-3, 7-34% (P < 0.0141)] were observed in mice treated with gefitinib. Furthermore, mice treated with 100 and 200 ppm of gefitinib exhibited 67.6% to 77.3% of the pancreas to be free from ductal lesions. Also, gefitinib reduced EGFR, proliferating cell nuclear antigen, cyclin D1, C 2 GNT, RhoA, β-catenin, p38, phospho-extracellular signal-regulated kinase, caveolin-1, and mucin and increased cyclin B1 in the pancreatic lesions/PDAC. In summary, these results show that gefitinib can prevent the progression of pancreatic cancer precursor lesions to PDAC in a preclinical model. The present study highlights the promise of chemoprevention and the potential usefulness of EGFR inhibitors in individuals at high risk for pancreatic cancer. Cancer Prev Res; 3(11); 1417-26. ©2010 AACR.

- by Misty Brewer
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- Immunohistochemistry, Cancer Prevention, Western blotting, Mice

Aim: To assess cytological, colposcopic and histological outcomes in women referred to a teaching hospital dysplasia clinic with low-grade changes on screening Pap smear. Methods: Analysis of a computerised database. Results: Repeating the Pap test was of little value. Fifteen percent of women with low-grade changes on the referral smear had biopsy proven high-grade change. There was little difference in biopsy proven high-grade change in women referred with an 'abnormal smear of uncertain significance' (23%) or 'an abnormal smear of uncertain significance-possible high-grade change' (24%). Conclusions: Given these findings and the current medico-legal climate, immediate referral of women with lowgrade changes on routine cytology is indicated, and seems a safer option than the more conservative approach of a repeat smear in 6 or 12 months. Further study of the usefulness of separating smears of uncertain significance into high-grade and low-grade categories is warranted. Consumer input into recommendations for management of Pap smear abnormalities is required.

- by Michael Quinn
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- Australian and New Zealand Cinema, Biopsy, Consumer, Squamous Cell Carcinoma

The outcome of radical external beam radiation therapy for 26 consecutive patients with invasive carcinoma of the penis treated between 1970 and 1985 was assessed to test the efficacy, and side effects of such treatment. Methods and Material: A retrospective review of 26 patients with invasive carcinoma of the penis and 11 patients with carcinoma in-situ of the penis, treated at the Princess Margaret Hospital between 1970 and 1985, was performed. Radiation treatment was delivered using @Co or 100-250 kv equipment to a dose ranging from 25 Gy in 10 fractions over 2 weeks to 60 Gy in 25 fractions over 5 weeks. The most often used XRT prescription was 50 Gy in 20 fractions over 4 weeks. Results: The 5-year overall actuarial survival for patients with invasive cancers was 62% (510) and the causespecific survival was 69% (rt9). The control of the primary lesion was 61.5%. Of five patients who progressed after initial radiotherapy, one patient was salvaged by penectomy. Of 11 patients who recurred after initial complete response, three did so in the penis alone and all were successfully salvaged by penectomy. Late complications were recorded in seven patients, two of whom underwent penectomy as a result. All patients with carcinoma in-situ achieved a complete response and, with follow-up ranging from 1 to 14 years, none recurred. Conclusion: We conclude that radiation therapy with surgery reserved for the management of local recurrence is an effective first line treatment for patients with carcinoma of the penis. Carcinoma penis, Radiotherapy, Results.

- by Tony Panzarella
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- Radiation Therapy, Survival Analysis, Radiotherapy, Squamous Cell Carcinoma

An inflammatory component consisting of cells and chemical mediators may influence the proliferation and dissemination of the oral squamous cell carcinoma (OSCC). In the present study, we evaluated the possible relationship between Ki-67, tumor-associated macrophages (TAMs), and COX-2 in OSCCs. In addition, the immunodetection of these proteins was associated with different histological grades of malignancy, including invasive and in situ tumors. Twenty-seven OSCC cases were examined by light microscopy using criteria adopted WHO, and immunohistochemistry for Ki-67, CD68, and COX-2 using EnVision System in invasive and in situ lesions. Immunohistochemical detection of these proteins was assessed and scored for COX-2, and results were compared with their histological grades of malignancy. A correlation between Ki-67, COX-2, and CD68 was not found. Histological grade of malignancy (HDM) was associated with the Ki-67 immunostaining (P = 0.00), but this was not observed regarding both C...

- by Christina Takiya
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- Dentistry, Cancer, Immunohistochemistry, Macrophages

The most commonly used staging system for cervical cancer is based on the International Federation of Gynaecology and Obstetrics (FIGO) staging system. Magnetic resonance imaging (MRI) has been accepted as the optimal tool for evaluation of the main prognostic factors and selection of therapeutic strategy. The purpose of this study was to compare the preoperative clinical examination FIGO staging findings with MRI and postoperative pathology report in females with primary cancer of the cervix. The study prospectively included 46 females consecutively hospitalized at the Department of Gynaecology and Obstetrics at the "Sestre milosrdnice" University Hospital Center in Zagreb. Interviews, clinical examination, transvaginal ultrasound and MRI were performed in all patients. In selected patients the surgical procedure was done and the correlation of clinical findings according to FIGO classifications, MRI and histopathological findings was completed. According to FIGO classifi...

- by Ksenija Klasnic
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- Anthropology, Magnetic Resonance Imaging, Prospective studies, Staging
- by Gani SUTEDJA
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- Cancer, Telomerase, Cancer Diagnosis, Squamous Cell Carcinoma

Induction of the expression of the Mr 67,000 high-affinity laminin receptor gene has been postulated as playing a role in the progression of human tumors to invasive cancers. We tested this hypothesis by examining histopathological sections of a large number of epithelial lesions of the genital tract associated with human papillomaviruses. In situ hybridization was performed with a riboprobe generated from a laminin receptor complementary DNA. Laminin receptor mRNA was expressed primarily in the less differentiated cells in normal squamous tissues and in a spectrum of squamous neoplasms. There was no net induction of mRNA per cell in intraepithelial or invasive squamous neoplasms relative to normal tissue. In contrast, laminin receptor mRNA was not expressed at a detectable level in normal glands of the uterine cervix but was dramatically induced in morphologically abnormal, human papillomavirus-positive glands, irrespective of the genotype of human papillomaviruses present. The ind...

- by Leendert Looijenga
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- Andrology, Risk, Ultrasound, tESTIS