Altered Expression Pattern of Topoisomerase IIα, in Ovarian Tumor Epithelial and Stromal Cells after Platinum-Based Chemotherapy

Abstract

OBJECTIVE: The aim of this study was to evaluate the expression of topoisomerase IIα (TOP2A) in epithelial and stromal cells of ovarian cancer. METHODS: TOP2A expression was analyzed in normal ovarian tissue and in laser-microdissected ovarian tumor epithelial and adjacent stromal cells using quantitative real time RT-PCR (n = 38), RNA in situ hybridization (n =13), and immunhistochemistry (n = 69). Results: TOP2A mRNA was detected by RNA in situ hybridization in all ovarian cancer samples, with stronger hybridization signals in tumor epithelial cells compared to adjacent stromal cells. The same expression pattern was found by immunohistochemistry (P = .0001). Very interestingly, specific changes of TOP2A were found in recurrent ovarian cancer after platinum-based chemotherapy: TOP2A expression decreased in tumor epithelial cells (P = .056) of recurrent ovarian cancer, whereas it increased in tumor adjacent stromal cells (P = .023) compared to primary ovarian cancer. CONCLUSION: TOP2A mRNA and protein expressions in ovarian cancer exhibit specific patterns in tumor epithelial and adjacent stromal cells, which are differentially modulated after platinum-based chemotherapy. These data support the possible importance of the stromal compartment in tumor progression and suggest that tumor stromal cells might be relevant to the development of chemotherapy resistance in ovarian cancer.

Keywords

• TOP2A
• ovarian cancer
• RNA in situ hybridization
• tumor stromal cells
• chemotherapy resistance