ABSTRACT
OBJECTIVE: Ovarian cancer is the most lethal of all gynecologic malignancies. It is characterized by the spread of intraperitoneal tumors, accumulation of ascites, and formation of tumor blood vessels. Cyclin I has been linked with angiogenesis-related proteins, like vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2), in human breast cancer. We examined whether an association exists between expression of cyclin I, VEGFR-2, clinicopathologic parameters and survival of patients with epithelial ovarian cancer (EOC). METHODS: Cyclin I and VEGFR-2 expressions were analyzed by immunohistochemistry in 55 human primary EOC tissue specimens. RESULTS: Cyclin I immunoreactivity was significantly correlated with VEGFR-2 (R=0.4587, P=0.0004), and immunolabeling of cyclin I and VEGFR-2 significantly correlated with cancer cells' proliferative activity evaluated using cyclin A labeling index as a marker (R=0.3107, P=0.0209 and R=0.4183, P=0.0015, respectively). VEGFR-2 immunostaining was significantly higher in advanced, poorly differentiated, and suboptimally resected EOCs compared to their counterparts (P<0.05). Finally, higher VEGFR-2 expression was significantly associated with shorter disease-free survival (P=0.0437). CONCLUSIONS: Our results indicate that elevated expression of cyclin I and VEGFR-2 is likely to provide a proliferative advantage to the EOC cells, and that cyclin I may be linked with angiogenesis in EOC. Higher expression of VEGFR-2 is associated with more advanced disease. Further investigation of cyclin I in ovarian cancer is needed to evaluate if cyclin I may become a novel target for an anticancer therapy.
Subject(s)
Cyclin I/metabolism , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Ovarian Epithelial , Cell Growth Processes/physiology , Cyclin I/biosynthesis , Female , Humans , Immunohistochemistry , Middle Aged , Neoplasms, Glandular and Epithelial/blood supply , Neoplasms, Glandular and Epithelial/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Ovarian Neoplasms/blood supply , Ovarian Neoplasms/pathology , Vascular Endothelial Growth Factor Receptor-2/biosynthesis , Young AdultABSTRACT
BACKGROUND: Neuropilin (NRP) may be used as a marker of lymphangiogenesis in malignant tumors. Significant correlations of the expression of NRP with tumor progression and overall survival prognosis were found in several cancer types. However; its potential role in epithelial ovarian cancer (EOC) has not been clarified. AIMS: The aim of the work was to study a possible correlation of neuropilin-1 (NRP-1) expression with selected clinical and histological features of EOC. MATERIAL AND METHODS: The study included 53 women (aged 23 to 81, mean 56.6 +/- 14.4 yrs), 38 of which were postmenopausal (71.7%). Immunohistochemical staining with a specific anti-NRP-1 antibody was performed in representative tumor tissue samples of patients with EOC. Both, percentage of stained lymphatic cells and intensity of staining were assessed under 200x magnification. The results were correlated with the menopausal status, FIGO stage, histological type and histological grade of EOC. RESULTS: Histological examination revealed that there were 27 cases of serous cancers (50%), 15 cases of mucinous cancer (28.3%) and 11 endometrioid cancers (20.7%). In 41.5% (n = 22) cases of EOC no NRP-1 staining was found, a weak (+) or strong (++) staining were found in 13 (24.5%) and 18 tumors, respectively There were no significant differences between neuropilin-1 expression and both menopausal status of women and histological type of EOC. Except for stage II, clinical EOC patients' FIGO stage was not correlated with the lack of expression (38.8% for stage I, 71.4% for stage II and 35.7% for stage III). CONCLUSION: We believe that neuropilin-1 expression is probably not related to clinical and histological features of epithelial ovarian cancer:
