stefania staibano - Academia.edu (original) (raw)

Papers by stefania staibano

Research paper thumbnail of Clinical and dermoscopic features of atypical Spitz tumors: A multicenter, retrospective, case-control study

Journal of the American Academy of Dermatology, 2015

Research paper thumbnail of Overexpression of cyclin-D1, bcl-2, and bax proteins, proliferating cell nuclear antigen (PCNA), and DNA-ploidy in squamous cell carcinoma of the oral cavity

Human Pathology, 1998

The prognostic role of the expression of bcl-1, bcl-2, bax, PCNA, and DNA-ploidy in a series of 2... more The prognostic role of the expression of bcl-1, bcl-2, bax, PCNA, and DNA-ploidy in a series of 25 oral squamous cell carcinoma (SCC) was investigated. The average age of the patients was 62.04 years (range, 27 to 81 years), with a sex ratio (M/F) of 23:2. The follow-up mean time was 2.24 years (range, 8 months to 8 years from surgery). Immunohistochemistry for PCNA, bcl-2, bcl-1, and bax proteins was carried out on 5-microm serial sections from formalin-fixed, paraffin-embedded tissue. The findings were compared with clinicopathologic data and with follow-up. The statistical evaluation of the results of the current study suggests that the low positivity for PCNA with a high positivity for bcl-2 protein are related to a better clinical behavior of the tumors. By converse, a high expression of PCNA, bax, and bcl-1 appears to correlate with a worse prognosis. All of our cases of SCC showed the presence of aneuploid populations, which was not correlated with the clinicopathologic parameters or with the overexpression of bcl-1, bcl-2, bax, and PCNA. Therefore, the aneuploidy per se did not predict the clinical evolution for the single cases of cancers. Nevertheless, once the parameters considered for the evaluation of DNA were examined in detail, it appeared that some of them, individually or combined with each other or with the expression of bcl-1, bcl-2, and bax, gained statistical significance in predicting the clinical evolution of SCC of our series. Particularly, high values of 2cDI and DNA-MG and the absence or reduction of the euploid population were associated with a short interval between surgery and recurrence or death, and this significance persisted when the simultaneous presence of overexpression of bcl-1 was considered.

Research paper thumbnail of Synergy between enzastaurin doxorubicin in inducing melanoma apoptosis

Pigment Cell & Melanoma Research, 2013

SummaryMelanoma is resistant to most standard chemotherapeutics. We analysed the combined effect ... more SummaryMelanoma is resistant to most standard chemotherapeutics. We analysed the combined effect of doxorubicin and enzastaurin on cell death of four melanoma cell lines, namely G361, SK‐MEL3, A375 and SAN. Enzastaurin IC50 was calculated by measure of growth inhibition with MTS assay and corresponded to 2 μM; the half maximal cytotoxicity of doxorubicin was obtained at 3 μM dose. Evaluation of combination index showed synergism (CI > 1) or additive effect (CI = 1) with all melanoma cell lines, with enzastaurin doses ≥0.6 μM and doxorubicin doses ≥1 μM. Combination of the two drugs resulted in increase in caspase 3 and 8 activation, in comparison with activation by single agents. Caspase 8 activation was impaired by TNFR‐1 blocking. Our results show doxorubicin‐stimulated production of TNFα, whereas enzastaurin‐stimulated TNFR‐1 expression on plasma membrane. The effect on TNFR‐1 appeared to be mediated by PKCζ inhibition. Taken together, our findings suggest that enzastaurin inc...

Research paper thumbnail of BAG3 protein delocalisation in prostate carcinoma

Tumor Biology, 2010

Despite the progressive increase of early diagnosis, a subset of prostate cancers show a metastas... more Despite the progressive increase of early diagnosis, a subset of prostate cancers show a metastasizing and lethal course, not always predictable upon the traditional prognostic parameters. The object of this study was to investigate the role of the survival co-chaperone protein BAG3 as a new prognostic marker for prostate cancer. BAG3 was detected by immunohistochemistry in 55 specimens of surgically removed prostate carcinomas and in 15 surgical specimens of non-neoplastic prostate tissues. Results were compared with clinic-pathological data and outcome of patients and statistically evaluated. BAG3 resulted expressed in all the cases: Non-neoplastic prostate tissue showed a cytoplasmatic staining with apical reinforcement, a finding which appears consistent with the reported connection of the protein with the membrane focal cell-adhesion complexes. In prostate carcinomas, BAG3 showed a progressive decrease of the expression level from well-to low-differentiated carcinoma, coupled with the loss of polarisation of the signal in metastasizing cases. These results indicate that BAG3 intra-cytoplasmic delocalisation is a specific feature of cancer versus non-neoplastic prostate and a candidate new marker for prediction of prostate cancer invasiveness and behaviour.

Research paper thumbnail of Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation

Research paper thumbnail of A Challenging Case of Primary Orbital Mesenchymal Chondrosarcoma

Orbit, 2010

Mesenchymal chondrosarcoma is an uncommon lesion of the bone and extraskeletal tissue involving v... more Mesenchymal chondrosarcoma is an uncommon lesion of the bone and extraskeletal tissue involving very rarely the orbit. Histopathological features of this lesion include: undifferentiated mesenchymal cells with islands of mature hyaline cartilage. We present a case of a 23-year-old man with primary orbital mesenchymal chondrosarcoma (OMC) with an uncommon management. This anecdotic report could be a contribution to the understanding of this unusual tumor.

Research paper thumbnail of Modulation of in vivo growth of thyroid tumor-derived cell lines by sense and antisense vascular endothelial growth factor gene

Research paper thumbnail of Estrogen receptor β expression in human prostate tissue

Molecular and Cellular Endocrinology, 2001

Research paper thumbnail of Variations of Proline-Rich Kinase Pyk2 Expression Correlate with Prostate Cancer Progression

Laboratory Investigation, 2001

Research paper thumbnail of Dermoscopy of pigmented skin lesions: Results of a consensus meeting via the Internet

Journal of the American Academy of Dermatology, 2003

Research paper thumbnail of Potentially malignant and malignant lesions of the lip. Role of silver staining nucleolar organizer regions, proliferating cell nuclear antigen, p53, and c-myc in differentiation and prognosis

Journal of Oral Pathology & Medicine, 2007

The cellular changes leading to carcinoma of the lip are still not completely understood. This st... more The cellular changes leading to carcinoma of the lip are still not completely understood. This study was carried out on 44 malignant and potentially malignant lesions of the lower lip [30 squamous cell carcinomas (SCC), 7 actinic cheilitis, 3 leukoplakias, and 4 nodal metastases from lower lip SCC]. Silver-stained nucleolar organizer regions (AgNORs) and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA), p53, and c-myc were evaluated on formalin-fixed, paraffin-embedded sections. The results indicate that the size and numbers of AgNORs and the percentage of PCNA-positive cells are sensitive parameters for discriminating between potentially malignant lesions and SCC, and for the prognostic sub-typing of lower lip SCC. Furthermore, while p53 positivity was found more frequently in high-grade carcinomas, p53-positive cellular clones were also found in some potentially malignant lesions, a finding probably related to ultraviolet-related cellular damage. These p53-positive lesions could be considered at higher risk of progression to malignancy than the p53-negative ones, although there is no evidence for this as yet. c-myc positivity was found only in some high-grade carcinomas and metastases, and appeared correlated with the later phases of lip carcinogenesis. The combined evaluation of the proliferation status, together with the changes in p53 and c-myc oncoproteins, might constitute useful markers for the prognostic evaluation of potentially malignant, as well as malignant, lesions of the lip.

Research paper thumbnail of Survivin, a Potential Early Predictor of Tumor Progression in the Oral Mucosa

Journal of Dental Research, 2003

Survivin is a recently described apoptosis inhibitor selectively over-expressed in most tumors. I... more Survivin is a recently described apoptosis inhibitor selectively over-expressed in most tumors. Immunohistochemistry was used to investigate a potential role of survivin as an early predictor of malignant transformation in precancerous and cancerous lesions of the oral cavity. Survivin was present in 10/30 cases (33%) of oral precancerous lesions without malignant progression, and in 15/16 cases (94%) of oral precancerous lesions evolved into full-blown squamous cell carcinoma. Tumors that progressed from these precancerous lesions retained widespread survivin positivity (100%). Variations among group means were highly statistically significant (p < 0.001). No significant correlation was found between survivin expression and the degree of dysplasia. High expression of cytoplasmic/nuclear survivin is an early event during oral carcinogenesis and may provide a useful tool for the identification of precancerous lesions at higher risk of progression into invasive carcinoma.

Research paper thumbnail of A possible role of catenin dyslocalization in pemphigus vulgaris pathogenesis

Journal of Cutaneous Pathology, 2001

Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucosa due to the pre... more Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucosa due to the presence of autoantibodies against the components of desmosomes. To date, less is known about the expression levels of beta- and gamma-catenins in blistering diseases. The objective of this study was to evaluate the role of beta- and gamma-catenins in the pathogenesis of acantholysis in pemphigus vulgaris. beta- and gamma-catenin expression was evaluated by immunohistochemistry in 30 cases of PV at various stages of the disease and, as controls, in 18 specimens of the skin/oral mucosa of healthy patients. Healthy skin and normal oral mucosa showed a strong beta- and gamma-catenin expression in basal and spinous layers with a prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of epithelium. In PV patients, cytoplasmic expression of gamma-catenin was detected in 28/30 cases, and in 19/30 cases of PV for beta-catenin. Moreover, a progressive displacement of the signal toward the nucleus was found in 14/30 cases for beta-catenin, with dyslocalization toward the nucleus, particularly in areas with intense acantholysis, and in 22/30 cases of PV for gamma-catenin. Abnormal distribution of gamma-catenin, consequent to PV IgG, may be considered a direct consequence of Dg3 dissociation from catenin. gamma-catenin likely plays a direct role in PV pathogenesis through its dyslocalization toward the nucleus or indirectly through the beta-catenin dyslocalization toward the nucleus, which is thought to induce transcription of selected target genes, such as uPAR.

Research paper thumbnail of Strict correlation between uPAR and plakoglobin expression in pemphigus vulgaris

Journal of Cutaneous Pathology, 2002

Recent studies have reported nuclear delocalization of plakoglobin in acantholytic pemphigus vulg... more Recent studies have reported nuclear delocalization of plakoglobin in acantholytic pemphigus vulgaris cells. The objective of this study was to evaluate the role of plakoglobin in the pathogenesis of acantholysis in pemphigus vulgaris (PV) and its relation with the urokinase-type plasminogen activator receptor (uPAR) expression. Plakoglobin and uPAR expressions were evaluated by immunohistochemistry in 22 cases of PV at various stages of the disease, and as controls in 18 specimens of skin/oral mucosa from healthy patients. Healthy skin/normal oral mucosa showed strong plakoglobin expression in the basal and spinous layers with prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of the epithelium. In PV patients, a progressive displacement of the plakoglobin signal toward the nucleus was found in 18/22 of the cases. Healthy skin/normal oral mucosa showed low uPAR expression with prevalent cellular membrane distribution. In the PV patients, strong uPAR expression was present in the acantholytic cells in 16/22 of the cases. There was direct correlation (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) between the uPAR expression and nuclear plakoglobin. The uPAR overexpression in acantholytic PV may be considered a direct consequence of plakoglobin abnormal distribution. Nuclear delocalization of plakoglobin, a direct consequence of plakoglobin-Dsg-3 dissociation induced by PV IgG, probably induces uPAR overexpression. This evidence suggests a central role for plakoglobin in PV pathogenesis because of its delocalization toward the nucleus, which is the probable cause of the uPAR gene expression.

Research paper thumbnail of Coexistence of Primary Gastric Giant Cell–Rich Leiomyosarcoma and Gastrointestinal Stromal Tumor

International Journal of Surgical Pathology, 2011

Leiomyosarcoma is one of the most common types of soft tissue sarcoma, usually seen in deep soft ... more Leiomyosarcoma is one of the most common types of soft tissue sarcoma, usually seen in deep soft tissues of the extremities and retroperitoneum. Leiomyosarcoma primarily involving the gastrointestinal tract is uncommon. This report presents a rare case of primary gastric giant cell-rich leiomyosarcoma associated with a gastrointestinal stromal tumor of the stomach in a 51-year-old man. The patient was alive with no evidence of recurrence 10 months later. To the authors’ knowledge, this association has not been previously reported.

Research paper thumbnail of Ovarian luteinized thecoma with sclerosing peritonitis in an adult woman treated with leuprolide and toremifene in complete remission at 5 years

Gynecologic Oncology, 2005

Luteinized thecoma of the ovary associated with sclerosing peritonitis is a rare pathologic condi... more Luteinized thecoma of the ovary associated with sclerosing peritonitis is a rare pathologic condition without a standard strategy of treatment. We present the case of an ovarian luteinizing sclerosing thecoma in a 39-year-old woman. The patient underwent three laparotomic operations for subocclusive symptoms, revealing in both occasions the presence of sclerosing peritonitis, with large abdominal masses, including cysts containing clear fluid. Treatment with toremifene 20 mg/day and leuprolide resulted in a dramatic improvement of the performance status and complete remission of all the abdominal lesions. After 60 months follow-up, the patient is still disease-free. Antiestrogens plus LHRH agonists might be a noninvasive, effective and well-tolerated therapy for sclerosing peritonitis in patient operated for luteinized thecomas.

Research paper thumbnail of Loss of Expression of Tumor Suppressor p16INK4 Protein in Human Primary Gastric Cancer Is Related to the Grade of Differentiation

Digestive Diseases, 2002

Background: Recent research has revealed a rapid increase in the number of alterations underlying... more Background: Recent research has revealed a rapid increase in the number of alterations underlying oncogenesis and the proteins which regulate the cell cycle. p16 is a cell cycle regulatory protein acting as a cyclin-dependent kinase inhibitor (CDKI). Because of its antiproliferative effect, p16 has been suggested to be a tumor suppressor gene. Deletions, mutations and functional inactivation of p16 occur with a frequency second only to p53 in most human malignancies. Aim: to evaluate the p16 protein expression in primary gastric cancer in order to understand the possible differences in relation to histotype and grade of tumors. Material and Methods: Immunohistochemical expression of p16 was investigated in matched normal and cancerous tissues from 70 patients with gastric cancer (52 intestinal and 18 diffuse type). Results: In non-cancerous gastric tissues the immunostaining of p16 was weak and limited to antral glands. In gastric cancer tissues, the enhanced immunoreactivity of p16...

Research paper thumbnail of PA.209 In-Vivo Histopathology via Standard Endoscopes. Results of a New High-Resolution Miniprobe-Based Confocal Microscope (Cellvizio-Gi, Mauna Kea Technologies)

Digestive and Liver Disease, 2008

Research paper thumbnail of Differential role of CD133 and CXCR4 in renal cell carcinoma

Research paper thumbnail of Abstract 4999: FK506 binding protein 51 (FKBP51) sustains stemness and the metastatic potential of malignant melanoma

Cancer Research, 2011

Background. FKBP51 is a cochaperone with peptidyl-prolyl isomerase activity that regulates severa... more Background. FKBP51 is a cochaperone with peptidyl-prolyl isomerase activity that regulates several biological processes in the cell, through protein-protein interaction. There is increasing evidence that FKBP51 hyperexpression is associated with cancer and this protein has a relevant role in sustaining cell growth, malignancy, and resistance to therapy. Very recently, we have found that FKBP51 is a protein associated with malignant melanoma. Its expression correlates with tumor aggressiveness and is maximal in metastatic lesions. Moreover, we have found that melanoma cancer stem cells express FKBP51 at levels higher than the other tumor cells and observed a 4 to 40 fold increase in the number of cancer stem cells, in cultures of melanoma cells stably transfected with FKBP51. Mitotic index, stemness features and angiogenesis are the main signs of aggressive melanoma. To better understand the role of FKBP51 in the biology and progression of melanoma, we attempted to investigate if thi...

Research paper thumbnail of Clinical and dermoscopic features of atypical Spitz tumors: A multicenter, retrospective, case-control study

Journal of the American Academy of Dermatology, 2015

Research paper thumbnail of Overexpression of cyclin-D1, bcl-2, and bax proteins, proliferating cell nuclear antigen (PCNA), and DNA-ploidy in squamous cell carcinoma of the oral cavity

Human Pathology, 1998

The prognostic role of the expression of bcl-1, bcl-2, bax, PCNA, and DNA-ploidy in a series of 2... more The prognostic role of the expression of bcl-1, bcl-2, bax, PCNA, and DNA-ploidy in a series of 25 oral squamous cell carcinoma (SCC) was investigated. The average age of the patients was 62.04 years (range, 27 to 81 years), with a sex ratio (M/F) of 23:2. The follow-up mean time was 2.24 years (range, 8 months to 8 years from surgery). Immunohistochemistry for PCNA, bcl-2, bcl-1, and bax proteins was carried out on 5-microm serial sections from formalin-fixed, paraffin-embedded tissue. The findings were compared with clinicopathologic data and with follow-up. The statistical evaluation of the results of the current study suggests that the low positivity for PCNA with a high positivity for bcl-2 protein are related to a better clinical behavior of the tumors. By converse, a high expression of PCNA, bax, and bcl-1 appears to correlate with a worse prognosis. All of our cases of SCC showed the presence of aneuploid populations, which was not correlated with the clinicopathologic parameters or with the overexpression of bcl-1, bcl-2, bax, and PCNA. Therefore, the aneuploidy per se did not predict the clinical evolution for the single cases of cancers. Nevertheless, once the parameters considered for the evaluation of DNA were examined in detail, it appeared that some of them, individually or combined with each other or with the expression of bcl-1, bcl-2, and bax, gained statistical significance in predicting the clinical evolution of SCC of our series. Particularly, high values of 2cDI and DNA-MG and the absence or reduction of the euploid population were associated with a short interval between surgery and recurrence or death, and this significance persisted when the simultaneous presence of overexpression of bcl-1 was considered.

Research paper thumbnail of Synergy between enzastaurin doxorubicin in inducing melanoma apoptosis

Pigment Cell & Melanoma Research, 2013

SummaryMelanoma is resistant to most standard chemotherapeutics. We analysed the combined effect ... more SummaryMelanoma is resistant to most standard chemotherapeutics. We analysed the combined effect of doxorubicin and enzastaurin on cell death of four melanoma cell lines, namely G361, SK‐MEL3, A375 and SAN. Enzastaurin IC50 was calculated by measure of growth inhibition with MTS assay and corresponded to 2 μM; the half maximal cytotoxicity of doxorubicin was obtained at 3 μM dose. Evaluation of combination index showed synergism (CI > 1) or additive effect (CI = 1) with all melanoma cell lines, with enzastaurin doses ≥0.6 μM and doxorubicin doses ≥1 μM. Combination of the two drugs resulted in increase in caspase 3 and 8 activation, in comparison with activation by single agents. Caspase 8 activation was impaired by TNFR‐1 blocking. Our results show doxorubicin‐stimulated production of TNFα, whereas enzastaurin‐stimulated TNFR‐1 expression on plasma membrane. The effect on TNFR‐1 appeared to be mediated by PKCζ inhibition. Taken together, our findings suggest that enzastaurin inc...

Research paper thumbnail of BAG3 protein delocalisation in prostate carcinoma

Tumor Biology, 2010

Despite the progressive increase of early diagnosis, a subset of prostate cancers show a metastas... more Despite the progressive increase of early diagnosis, a subset of prostate cancers show a metastasizing and lethal course, not always predictable upon the traditional prognostic parameters. The object of this study was to investigate the role of the survival co-chaperone protein BAG3 as a new prognostic marker for prostate cancer. BAG3 was detected by immunohistochemistry in 55 specimens of surgically removed prostate carcinomas and in 15 surgical specimens of non-neoplastic prostate tissues. Results were compared with clinic-pathological data and outcome of patients and statistically evaluated. BAG3 resulted expressed in all the cases: Non-neoplastic prostate tissue showed a cytoplasmatic staining with apical reinforcement, a finding which appears consistent with the reported connection of the protein with the membrane focal cell-adhesion complexes. In prostate carcinomas, BAG3 showed a progressive decrease of the expression level from well-to low-differentiated carcinoma, coupled with the loss of polarisation of the signal in metastasizing cases. These results indicate that BAG3 intra-cytoplasmic delocalisation is a specific feature of cancer versus non-neoplastic prostate and a candidate new marker for prediction of prostate cancer invasiveness and behaviour.

Research paper thumbnail of Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation

Research paper thumbnail of A Challenging Case of Primary Orbital Mesenchymal Chondrosarcoma

Orbit, 2010

Mesenchymal chondrosarcoma is an uncommon lesion of the bone and extraskeletal tissue involving v... more Mesenchymal chondrosarcoma is an uncommon lesion of the bone and extraskeletal tissue involving very rarely the orbit. Histopathological features of this lesion include: undifferentiated mesenchymal cells with islands of mature hyaline cartilage. We present a case of a 23-year-old man with primary orbital mesenchymal chondrosarcoma (OMC) with an uncommon management. This anecdotic report could be a contribution to the understanding of this unusual tumor.

Research paper thumbnail of Modulation of in vivo growth of thyroid tumor-derived cell lines by sense and antisense vascular endothelial growth factor gene

Research paper thumbnail of Estrogen receptor β expression in human prostate tissue

Molecular and Cellular Endocrinology, 2001

Research paper thumbnail of Variations of Proline-Rich Kinase Pyk2 Expression Correlate with Prostate Cancer Progression

Laboratory Investigation, 2001

Research paper thumbnail of Dermoscopy of pigmented skin lesions: Results of a consensus meeting via the Internet

Journal of the American Academy of Dermatology, 2003

Research paper thumbnail of Potentially malignant and malignant lesions of the lip. Role of silver staining nucleolar organizer regions, proliferating cell nuclear antigen, p53, and c-myc in differentiation and prognosis

Journal of Oral Pathology & Medicine, 2007

The cellular changes leading to carcinoma of the lip are still not completely understood. This st... more The cellular changes leading to carcinoma of the lip are still not completely understood. This study was carried out on 44 malignant and potentially malignant lesions of the lower lip [30 squamous cell carcinomas (SCC), 7 actinic cheilitis, 3 leukoplakias, and 4 nodal metastases from lower lip SCC]. Silver-stained nucleolar organizer regions (AgNORs) and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA), p53, and c-myc were evaluated on formalin-fixed, paraffin-embedded sections. The results indicate that the size and numbers of AgNORs and the percentage of PCNA-positive cells are sensitive parameters for discriminating between potentially malignant lesions and SCC, and for the prognostic sub-typing of lower lip SCC. Furthermore, while p53 positivity was found more frequently in high-grade carcinomas, p53-positive cellular clones were also found in some potentially malignant lesions, a finding probably related to ultraviolet-related cellular damage. These p53-positive lesions could be considered at higher risk of progression to malignancy than the p53-negative ones, although there is no evidence for this as yet. c-myc positivity was found only in some high-grade carcinomas and metastases, and appeared correlated with the later phases of lip carcinogenesis. The combined evaluation of the proliferation status, together with the changes in p53 and c-myc oncoproteins, might constitute useful markers for the prognostic evaluation of potentially malignant, as well as malignant, lesions of the lip.

Research paper thumbnail of Survivin, a Potential Early Predictor of Tumor Progression in the Oral Mucosa

Journal of Dental Research, 2003

Survivin is a recently described apoptosis inhibitor selectively over-expressed in most tumors. I... more Survivin is a recently described apoptosis inhibitor selectively over-expressed in most tumors. Immunohistochemistry was used to investigate a potential role of survivin as an early predictor of malignant transformation in precancerous and cancerous lesions of the oral cavity. Survivin was present in 10/30 cases (33%) of oral precancerous lesions without malignant progression, and in 15/16 cases (94%) of oral precancerous lesions evolved into full-blown squamous cell carcinoma. Tumors that progressed from these precancerous lesions retained widespread survivin positivity (100%). Variations among group means were highly statistically significant (p < 0.001). No significant correlation was found between survivin expression and the degree of dysplasia. High expression of cytoplasmic/nuclear survivin is an early event during oral carcinogenesis and may provide a useful tool for the identification of precancerous lesions at higher risk of progression into invasive carcinoma.

Research paper thumbnail of A possible role of catenin dyslocalization in pemphigus vulgaris pathogenesis

Journal of Cutaneous Pathology, 2001

Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucosa due to the pre... more Pemphigus vulgaris (PV) is an autoimmune blistering disease of the skin and mucosa due to the presence of autoantibodies against the components of desmosomes. To date, less is known about the expression levels of beta- and gamma-catenins in blistering diseases. The objective of this study was to evaluate the role of beta- and gamma-catenins in the pathogenesis of acantholysis in pemphigus vulgaris. beta- and gamma-catenin expression was evaluated by immunohistochemistry in 30 cases of PV at various stages of the disease and, as controls, in 18 specimens of the skin/oral mucosa of healthy patients. Healthy skin and normal oral mucosa showed a strong beta- and gamma-catenin expression in basal and spinous layers with a prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of epithelium. In PV patients, cytoplasmic expression of gamma-catenin was detected in 28/30 cases, and in 19/30 cases of PV for beta-catenin. Moreover, a progressive displacement of the signal toward the nucleus was found in 14/30 cases for beta-catenin, with dyslocalization toward the nucleus, particularly in areas with intense acantholysis, and in 22/30 cases of PV for gamma-catenin. Abnormal distribution of gamma-catenin, consequent to PV IgG, may be considered a direct consequence of Dg3 dissociation from catenin. gamma-catenin likely plays a direct role in PV pathogenesis through its dyslocalization toward the nucleus or indirectly through the beta-catenin dyslocalization toward the nucleus, which is thought to induce transcription of selected target genes, such as uPAR.

Research paper thumbnail of Strict correlation between uPAR and plakoglobin expression in pemphigus vulgaris

Journal of Cutaneous Pathology, 2002

Recent studies have reported nuclear delocalization of plakoglobin in acantholytic pemphigus vulg... more Recent studies have reported nuclear delocalization of plakoglobin in acantholytic pemphigus vulgaris cells. The objective of this study was to evaluate the role of plakoglobin in the pathogenesis of acantholysis in pemphigus vulgaris (PV) and its relation with the urokinase-type plasminogen activator receptor (uPAR) expression. Plakoglobin and uPAR expressions were evaluated by immunohistochemistry in 22 cases of PV at various stages of the disease, and as controls in 18 specimens of skin/oral mucosa from healthy patients. Healthy skin/normal oral mucosa showed strong plakoglobin expression in the basal and spinous layers with prevalent cellular membrane distribution; the intensity of staining progressively decreased toward the superficial layers of the epithelium. In PV patients, a progressive displacement of the plakoglobin signal toward the nucleus was found in 18/22 of the cases. Healthy skin/normal oral mucosa showed low uPAR expression with prevalent cellular membrane distribution. In the PV patients, strong uPAR expression was present in the acantholytic cells in 16/22 of the cases. There was direct correlation (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) between the uPAR expression and nuclear plakoglobin. The uPAR overexpression in acantholytic PV may be considered a direct consequence of plakoglobin abnormal distribution. Nuclear delocalization of plakoglobin, a direct consequence of plakoglobin-Dsg-3 dissociation induced by PV IgG, probably induces uPAR overexpression. This evidence suggests a central role for plakoglobin in PV pathogenesis because of its delocalization toward the nucleus, which is the probable cause of the uPAR gene expression.

Research paper thumbnail of Coexistence of Primary Gastric Giant Cell–Rich Leiomyosarcoma and Gastrointestinal Stromal Tumor

International Journal of Surgical Pathology, 2011

Leiomyosarcoma is one of the most common types of soft tissue sarcoma, usually seen in deep soft ... more Leiomyosarcoma is one of the most common types of soft tissue sarcoma, usually seen in deep soft tissues of the extremities and retroperitoneum. Leiomyosarcoma primarily involving the gastrointestinal tract is uncommon. This report presents a rare case of primary gastric giant cell-rich leiomyosarcoma associated with a gastrointestinal stromal tumor of the stomach in a 51-year-old man. The patient was alive with no evidence of recurrence 10 months later. To the authors’ knowledge, this association has not been previously reported.

Research paper thumbnail of Ovarian luteinized thecoma with sclerosing peritonitis in an adult woman treated with leuprolide and toremifene in complete remission at 5 years

Gynecologic Oncology, 2005

Luteinized thecoma of the ovary associated with sclerosing peritonitis is a rare pathologic condi... more Luteinized thecoma of the ovary associated with sclerosing peritonitis is a rare pathologic condition without a standard strategy of treatment. We present the case of an ovarian luteinizing sclerosing thecoma in a 39-year-old woman. The patient underwent three laparotomic operations for subocclusive symptoms, revealing in both occasions the presence of sclerosing peritonitis, with large abdominal masses, including cysts containing clear fluid. Treatment with toremifene 20 mg/day and leuprolide resulted in a dramatic improvement of the performance status and complete remission of all the abdominal lesions. After 60 months follow-up, the patient is still disease-free. Antiestrogens plus LHRH agonists might be a noninvasive, effective and well-tolerated therapy for sclerosing peritonitis in patient operated for luteinized thecomas.

Research paper thumbnail of Loss of Expression of Tumor Suppressor p16INK4 Protein in Human Primary Gastric Cancer Is Related to the Grade of Differentiation

Digestive Diseases, 2002

Background: Recent research has revealed a rapid increase in the number of alterations underlying... more Background: Recent research has revealed a rapid increase in the number of alterations underlying oncogenesis and the proteins which regulate the cell cycle. p16 is a cell cycle regulatory protein acting as a cyclin-dependent kinase inhibitor (CDKI). Because of its antiproliferative effect, p16 has been suggested to be a tumor suppressor gene. Deletions, mutations and functional inactivation of p16 occur with a frequency second only to p53 in most human malignancies. Aim: to evaluate the p16 protein expression in primary gastric cancer in order to understand the possible differences in relation to histotype and grade of tumors. Material and Methods: Immunohistochemical expression of p16 was investigated in matched normal and cancerous tissues from 70 patients with gastric cancer (52 intestinal and 18 diffuse type). Results: In non-cancerous gastric tissues the immunostaining of p16 was weak and limited to antral glands. In gastric cancer tissues, the enhanced immunoreactivity of p16...

Research paper thumbnail of PA.209 In-Vivo Histopathology via Standard Endoscopes. Results of a New High-Resolution Miniprobe-Based Confocal Microscope (Cellvizio-Gi, Mauna Kea Technologies)

Digestive and Liver Disease, 2008

Research paper thumbnail of Differential role of CD133 and CXCR4 in renal cell carcinoma

Research paper thumbnail of Abstract 4999: FK506 binding protein 51 (FKBP51) sustains stemness and the metastatic potential of malignant melanoma

Cancer Research, 2011

Background. FKBP51 is a cochaperone with peptidyl-prolyl isomerase activity that regulates severa... more Background. FKBP51 is a cochaperone with peptidyl-prolyl isomerase activity that regulates several biological processes in the cell, through protein-protein interaction. There is increasing evidence that FKBP51 hyperexpression is associated with cancer and this protein has a relevant role in sustaining cell growth, malignancy, and resistance to therapy. Very recently, we have found that FKBP51 is a protein associated with malignant melanoma. Its expression correlates with tumor aggressiveness and is maximal in metastatic lesions. Moreover, we have found that melanoma cancer stem cells express FKBP51 at levels higher than the other tumor cells and observed a 4 to 40 fold increase in the number of cancer stem cells, in cultures of melanoma cells stably transfected with FKBP51. Mitotic index, stemness features and angiogenesis are the main signs of aggressive melanoma. To better understand the role of FKBP51 in the biology and progression of melanoma, we attempted to investigate if thi...