Correlation of Immunohistochemical Expression of MDR1, MRP1, Topoisomerase IIalpha with Prognostic Factors and Histoculture Drug Response Assay (HDRA) Result in Breast Carcinoma

Purpose: Drug resistance plays an important role in the failure of chemotherapy in breast cancer. The purpose of the study was to investigate the chemosensitive and chemoresistance indices of breast carcinomas and see if the in vitro chemosensitivity test correlated with the prognostic indices. Methods: The immunohistochemical expressions of MDR1, MRP1 and topoisomerase IIα (topo IIα) were studied and then correlated these with the in vitro chemosensitivities using the histoculture drug response assay (HDRA) and clinicopathological factors in 51 breast carcinomas. Results: In the breast carcinomas examined, the immunohistochemical expressions of MDR1, MRP1 and topo IIα were strongly observed in 26 (51.0%), 16 (32.0%), 15 (31.3%) carcinomas, respectively. The MRP1 was more frequently expressed in poorly differentiated carcinomas (P= 0.006), and those of MDR1 and topo IIα were more frequently observed in tumor overexpressing cerbB2 (P=0.038, P=0.036). The expression of MDR1 was related to that of topo IIα (P=0.015). Comparing these markers with the in vitro chemosensitivities to cyclophosphamide, 5-FU, adriamycin, taxol and taxotere, no correlations were found between the expression of MDR1, MRP1, and topo IIα but from the chemosensitivity using the HDRA, the growth inhibition rate for cyclophosphamide was higher in MRP1 expressing carcinomas (P=0.009). Conclusion: MDR1, MRP1 and topo IIα were all found to be associated with the poor prognostic indices, but assessment of their immunohistochemical expressions did not allow for prediction of the response to chemotherapy by the in vitro chemosensitivity test in breast carcinomas. (Journal of Korean Breast Cancer Society 2004;7:228-235)