Further studies are required to better understand the role of gamma/delta T cells in ovarian carcinoma, yet these data underline the importance of host immune response to cancer and the need to better study immune mechanisms to modulate the therapeutic treatment of cancer.
The aim of the study was to test the prognostic value of the microvessel density (MVD) within the tumor and the vascular endothelial growth factor (VEGF) expression on clinical response to chemotherapy, on brief disease-free interval, and on cause-specific survival in advanced ovarian serous carcinoma. We evaluated 83 ovarian carcinomas homogeneous for stage, type and grade histologic, surgical, and chemotherapeutic treatment. Brief disease-free interval and cause-specific survival rates (Kaplan-Meier method) were compared using the log-rank test. A multivariate analysis (Cox-proportional hazards model) was used to determine the independent effect of each variable on prognosis. Overall 60 and 120 months cause-specific survival rates were 27.7% and 2.4%, respectively. The brief disease-free interval rate was 66.2%. In univariate analysis, VEGF (P = 0.0001 and P = 0.016), MVD (P < 0.0005), and the FIGO stage IIIC even more than FIGO stage IIIA (P = 0.01 and P < 0.0005, respectively) were associated with survival and brief disease-free interval, and the residual tumor was associated with survival (P = 0.021). In multivariate analysis, the factors that were independent predictors of survival were MVD (P < 0.0005), VEGF (P = 0.027), and the FIGO stage IIIC even more than FIGO stage IIIA (P = 0.013). Moreover, MVD was an independent predictor also of brief disease relapse (P = 0.001). Both MVD and VEGF were correlated with clinical response to chemotherapy (P = 0.01 and P = 0.037). Our data suggest that MVD and VEGF may have prognostic significance in advanced ovarian serous carcinoma.
The aim of the study is to test the prognostic value of cyclooxygenase-2 (COX-2) and P-glycoprotein in relation to responsiveness to chemotherapy in ovarian carcinoma patients with "shorter and longer" survival. We evaluated 52 ovarian carcinomas homogeneous for stage, histologic type, grade of differentiation, and surgical and chemotherapeutic treatment. Twenty-eight of the patients had died of progression of disease no later than 2 years after primary surgical treatment, while 24 patients were alive with no evident disease 5 years after primary surgical treatment. In logistic regression analysis, COX-2 and P-glycoprotein, when analyzed one by one, are significant (P= 0.017 and P < 0.0005, respectively). P-glycoprotein is correlated with COX-2 (P= 0.008, Fisher's exact test); moreover, both COX-2 and the P-glycoprotein are correlated with clinical response to chemotherapy (P= 0.022 and P < 0.0005, respectively, Chi-square test). Our data suggest that COX-2 and P-glycoprotein may have prognostic significance in advanced ovarian serous carcinoma. The COX-2 and the P-glycoprotein overexpressions are correlated to one another and both with a progression of disease during the first-line chemotherapy. The administration of a COX-2 inhibitor in association with chemotherapy in ovarian carcinoma patients may improve the tumor chemosensibility and the overall survival.
c-KIT is also expressed in ovarian carcinoma and it is statistically correlated with chemotherapy resistance. This study suggests the necessity for clinical trials confirming the utility of the tyrosine kinase inhibitor, STI571, in ovarian advanced cancer patients with c-KIT overexpression when these patients have shown no clinical response to conventional chemotherapy.
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.
Conclusion: 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.
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