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Diagnostic Cytopathology 03/2008; 36(2):113-4. · 1.16 Impact Factor
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ABSTRACT: The bcl-2 protein is a membrane protein involved in prolonging cell survival by inhibiting apoptosis. The HER-2 oncogene, which is located on chromosome 17 and encodes for a tyrosine-kinase growth factor receptor, is amplified and HER-2/neu is overexpressed in 25% to 30% of breast carcinomas. The authors analyzed the bcl-2 expression and the bcl-2 gene and HER-2/neu overexpression and amplification in FIGO stage IIIC, serous, G3, ovarian carcinomas obtained from living patients who had no evident disease 5 years after primary treatment compared with ovarian carcinomas obtained from patients, matched for stage, grade of differentiation, and treatment, who had died of progression of disease no later than 2 years after primary treatment. bcl-2 overexpression was statistically correlated with progression of disease during first-line chemotherapy (P=0.021). The HER-2/neu status was found not to correlate with progression of disease during first-line chemotherapy. Both bcl-2 and HER-2/neu expression were not statistically associated with the clinical outcome of ovarian cancer patients. Gene amplification of the HER-2/neu chromosome 17 was found in all the HER-2/neu, 3+ score, positive-staining ovarian carcinomas. None of the analyzed samples revealed a translocation t(14;18)(q32;q21) in the bcl-2 gene. The knowledge of additional prognostic or even predictive factors, such as bcl-2 expression, in patients with advanced ovarian carcinoma before the primary chemotherapeutic treatment may help in the management of patients who require a more tailored treatment. In addition, the gene amplification of the HER-2/neu suggests that HER-2 is a potential target for treatment in ovarian cancer.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 07/2006; 14(2):181-6. · 1.63 Impact Factor
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American journal of obstetrics and gynecology 05/2006; 194(4):1203; author reply 1204. · 3.28 Impact Factor
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ABSTRACT: CA-125 is elevated in the serum of the majority of ovarian carcinoma patients. Cyclooxygenase-2 is an enzyme whose synthesis is upgraded by several cytokines, growth factors, and tumor promoters.
We analyzed cyclooxygenase-2, preoperative CA-125 levels, and CA-125 levels during chemotherapy in 41 FIGO stage III, grade 3, ovarian serous carcinoma patients in relation to survival with a logistic regression. The correlation of cyclooxygenase-2 expression and CA-125 preoperative level with clinical responsiveness to chemotherapy was studied according to Fisher's exact test. We compared 23 patients living with no evident disease five years after primary treatment to 18 patients who had died of progression of disease no later than two years after primary treatment.
Cyclooxygenase-2 overexpression (p = 0.014 and p = 0.036) and preoperative CA-125 level (p = 0.012 and p = 0.029) were found to be independent predictors of survival in univariate and multivariate analyses. Cyclooxygenase-2 and CA-125 level were correlated to responsiveness to chemotherapy (p = 0.003 and p = 0.036, respectively; Fisher's exact test). The patients with a CA-125 level <35 U/ml after two cycles of chemotherapy showed a longer survival (p = 0.008). The median preoperative CA-125 was 195 in high survival patients and 650 in low survival patients (p= 0.004, Wilcoxon Mann-Whitney test).
Cyclooxygenase-2 overexpression and CA-125 levels may help the management of ovarian cancer patients, permitting the selection of more aggressive and tailored first-line therapy.
Acta Obstetricia Et Gynecologica Scandinavica 01/2006; 85(4):493-8. · 1.77 Impact Factor
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Acta Obstetricia Et Gynecologica Scandinavica - ACTA OBSTET GYNECOL SCAND. 01/2006; 85(4):493-498.
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Gynecologic Oncology 09/2005; 98(2):334-5. · 3.89 Impact Factor
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ABSTRACT: We analyzed in advanced ovarian serous G3 carcinoma the correlation between epidermal growth factor receptor (EGFR) overexpression and tumor angiogenesis and their relation with clinical outcome. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) were statistically correlated with disease-free interval and death from disease both in univariate and multivariate analyses while EGFR expression was not correlated with clinical outcome. MVD was significantly associated with progression of disease during chemotherapy while VEGF and EGFR expression were not correlated with responsiveness to chemotherapy (Fisher's exact test). VEGF expression was correlated with MVD (Fisher's exact test). EGFR showed a trend to correlation with MVD. Further studies focusing on the use of angiogenesis inhibitors in addition to EGFR inhibitors on ovarian carcinoma cells may produce therapeutic strategies in the selection of tailored therapies in ovarian cancer patients.
International Journal of Surgical Pathology 05/2005; 13(2):135-42. · 1.00 Impact Factor
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Archives of pathology & laboratory medicine 05/2005; 129(4):e103-4. · 2.58 Impact Factor
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Gynecologic Oncology 07/2004; 93(3):718. · 3.89 Impact Factor
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ABSTRACT: Primary and secondary mucinous tumors can involve the ovaries and have similar histologic appearances. The differential diagnosis is important for surgical and chemotherapeutic treatment and for the prognosis, but often it is extremely difficult. This article discusses an immunohistochemical panel that includes carcinoembryonic antigen (CEA), cytokeratin (CK) 7, CK20, CA125, CA19.9, and a new marker, CDX-2, for the distinction between primary ovarian mucinous carcinomas and metastatic (intestinal) ovarian tumors. Forty-three cases representing primary and secondary ovarian tumors were considered and consisted of 14 primary mucinous ovarian carcinomas (PMOCs) and 29 secondary (intestinal) ovarian tumors (SIOTs). Fisher exact test was performed to evaluate the reliability of the respective antibodies to discriminate between PMOCs and SIOTs. CDX-2 was diffusely positive in all SIOTs and was expressed focally in 3 cases (21.42%) of PMOCs. CK7 was diffusely positive in 13 cases (44.82%) of SIOTs and in 13 cases (92.85%) of PMOCs. CK20 was diffusely positive in 17 cases (58.62%) of SIOTs and in 6 cases (42.85%) of PMOCs. CEA was diffusely positive in 28 cases (96.55%) of SlOTs and in 12 cases (85.71%) of PMOCs. CA 19.9 was positive in all SIOTs and in 12 cases (85.71%) of PMOCs. CA125 was positive in 3 cases (10.34%) of SIOTs and in 4 cases (28.57%) of PMOCs. CK7 and especially CDX-2, a specific and sensitive marker, can aid pathologists in making a differential diagnosis (P = 0.003 and P < 0.0005, respectively), whereas CEA, CK20, CA125, and CA 19.9 markers are not high enough to distinguish between primary and secondary mucinous ovarian tumors.
Applied immunohistochemistry & molecular morphology: AIMM / official publication of the Society for Applied Immunohistochemistry 07/2004; 12(2):127-31. · 1.63 Impact Factor
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ABSTRACT: Uterine leiomyosarcomas are rare tumors characterized by their resistance to chemotherapy and radiation treatment. Surgery is the primary method of treatment, but for patients with unresectable disease, alternate therapeutic options are clearly warranted. According to initial observations of c-KIT expression, correlation with a bad prognosis, and the successful therapeutic possibility of STI571 in gastrointestinal stromal tumors, the data have encouraged us to study c-KIT expression in these tumors.
We analyzed the expression of c-KIT and genetic assessment of exon 11 of c-kit gene in 32 uterine leiomyosarcomas.
In 17 cases (53.1%), we observed a c-KIT expression in tumor cells. Of the 17 patients with distinct c-KIT-positive immunoreactivity, eight had I or II stage disease and nine had III or IV stage disease. Molecular genetic analysis of exon 11, analyzed by direct DNA sequencing, was performed for all of the c-KIT-positive uterine leiomyosarcomas. No mutations were found.
The conventional chemotherapy in leiomyosarcomas appears to be ineffective for patients with metastatic or unresectable disease, and the management of these patients poses a special problem. In these women, new therapeutic strategies are warranted. The treatment with STI571 in leiomyosarcoma patients might be hypothesized, because uterine leiomyosarcomas also express c-KIT.
Clinical Cancer Research 06/2004; 10(10):3500-3. · 7.74 Impact Factor
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ABSTRACT: Cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and microvessel density (MVD) have been reported to be significantly related to carcinogenesis and to tumoral progression. The aim of the study was to analyse immunohistochemically the overexpression of COX-2 and VEGF, and the MVD between one another, and also in relation with clinical outcome in ovarian carcinoma. We selected 52 patients with ovarian carcinoma homogeneous by stage, type and histological grade, surgical and chemotherapeutic treatment. Of these, 28 patients had died of progression of their disease within 2 years of their primary surgical treatment, while 24 patients were alive with no evident disease at 5 years from the primary surgical treatment. The differences of the COX-2 status, the MVD and the VEGF expression in the two groups of ovarian carcinoma patients with low and high survival rate, respectively, were calculated according to the Fisher's exact test and the logistic regression. The shift in location of MVD in the two groups of patients was calculated according to the Wilcoxon Mann-Whitney test. MVD was correlated with COX-2 and VEGF overexpression (P=0.009 and P=0.003, respectively), COX-2 and VEGF were correlated to one another (P=0.044). In logistic regression analysis, COX-2, VEGF, and MVD were significant (P=0.017, P=0.008, P<0.0005, respectively). In the cases with low survival rate, the average MVD was 102, while in the cases with high survival rate the average MVD was 40.5 (P<0.0005). The evaluation of the COX-2, the VEGF and the MVD may give additional prognostic information for first-line chemotherapy and clinical outcome of patients with ovarian carcinoma and may encourage selection of more tailored therapies. Angiogenesis inhibitors or COX-inhibitors probably can have synergistic effects with chemotherapy.
Oncology Reports 03/2004; 11(2):309-13. · 1.84 Impact Factor
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ABSTRACT: To correlate the treatment used in uterine sarcoma with outcome. The prognostic importance of pathology, clinical parameters and treatment are analyzed.
Forty patients (median age, 59 years; range, 37-85) with histologically verified uterine sarcoma were identified from a database compiled at the University of Florence from 1980 to 2001. Patients were followed for a median of 54 months (range, 3 months to 10 years). Twenty-four patients had leiomyosarcoma, 12 patients had mixed mullerian tumors, and 3 patients had endometrial stromal sarcoma. Stage I, II, III and IV tumors were identified in 22, 2, 9 and 7 patients, respectively. High, intermediate, low and unspecified grade sarcoma occurred in 9, 4, 5 and 22 patients, respectively.
At the time of analysis, 58% of patients had died and 42% were alive, with a median survival of 2 years from the initial diagnosis. Cause-specific survival for the entire group was 81%, 41% and 25% at 1, 3 and 5 years, respectively. In our series, univariate analysis for cause-specific survival did not demonstrate statistical significance for histology, grade, stage or age. There appeared to be a significant impact for postoperative radiotherapy in reducing local recurrence with a total dose higher than 50 Gy.
Our data favor treatment for uterine sarcoma with radical surgery plus irradiation, even in elderly patients.
Tumori 91(2):139-43. · 0.86 Impact Factor
