Role of podoplanin, E-cadherin, Ki-67 in the dissemination of tumor cells in ovarian surface epithelial carcinoma-An immunohistochemical study

Abstract

Background/aim: To understand the biological behaviour, ovarian carcinoma should be approached as a complex tissue composed of tumor cells, ECM proteins, endothelial cells, fibroblasts, inflammatory cells and lymphatics. We aimed to investigate the role of proliferation index of the tumor cells, cell adheshion molecules and lymphangiogenesis in the dissemination of tumor in ovarian surface epithelial carcinomas using suitable antibodies.

Materials and methods: Fifty-nine cases of ovarian carcinoma were assessed immunohistochemically to quantify the intratumoral and peritumoral LVD, podoplanin expression in stroma, E-cadherin expression and proliferation index of the tumor cells. Descriptive statistics were done stratifying the cases into early stage(FIGO-I) and advanced stage (FIGO-II,III,IV).Receiver operating curve was applied to determine the cut off of intratumoral LVD, peritumoral LVD, Ki-67 to discriminate early stage and advanced stage disease and the cut offs were validated by generating regression model.

Results: Intratumoral LVD (p = 0.001), peritumoral LVD (p = 0.000), high Ki-67 (p = 0.000), podoplanin expressing cancer associated fibroblasts (p = 0.002) and macrophages expressing podoplanin (p = 0.003) were significantly associated with advanced stage disease. Intratumoral LVD, peritumoral LVD and Ki67 at cut offs of 3.5, 9.5 and 30 % emerged as discriminators of early stage disease from advanced stage disease by ROC curve analysis. Peritumoral LVD > 9.5 had the highest odds of advanced disease (OR-33.948, CI-4.631-38.622).

Conclusion: OSECs with intratumoral LVD > 3.5, peritumoral LVD > 9.5 and Ki-67 > 30 % should be considered for aggressive chemotherapy and frequent follow-up. Peritumoral LVD and podoplanin expression in components of tumor stroma have a determinant role in tumor dissemination in OSEC.

Keywords: Cell adheshion; Collective cancer cell migration; Epithelial-mesenchymal transition; Lymphangiogenesis; Tumor associated macrophages; Tumor microenvironment.