Tumor- and stromal cell-specific expression of topoisomerase IIα and HER-2/neu in primary and recurrent ovarian cancer: Results of a prospective study.

The aim of the present study was to evaluate the expression of topoisomerase IIα (TOP2A) and HER-2 in tumor epithelial and adjacent stromal cells in ovarian cancer (OvCa). Immunohistochemistry for TOP2A and HER-2 was performed on 50 OvCa specimens from the Tumor Bank of Ovarian Cancer, and was correlated to established clinicopathological parameters. TOP2A was expressed in 98% and HER-2 in 52% of the OvCa specimens. Moderate expression of TOP2A was detected in 72% of the adjacent stromal cells. TOP2A and HER-2 were strongly expressed in the tumor epithelial cells of primary OvCa, but reduced in recurrent OvCa. Stromal expression of TOP2A increased in recurrent OvCa after platinum-based chemotherapy. In conclusion, distinct epithelial and stromal cell expression of TOP2A and HER-2 is a novel feature in the tumor biology of OvCa. Differential cellular expression of TOP2A in relation to previous chemotherapy probably reflects a modified activity of the 'stromal compartment' in drug resistance. Thus, analysis of TOP2A expression in tumor and stromal OvCa cells can aid in identifying subgroups of patients who may have a more favorable response to chemotherapy.