Immunohistochemical analysis of possible chemoresistance markers identified by micro-arrays on serous ovarian carcinomas

Abstract

Using the DNA microarray technology, we have identified genes that are differentially expressed in chemosensitive and chemoresistant ovarian serous papillary carcinomas and could potentially distinguish ovarian cancer patients based on their response to chemotherapy. The present study aims to evaluate the clinical usefulness of overexpression of selected genes by immunohistochemistry. Our cohort included 158 women who were operated on and received chemotherapy for an advanced serous papillary ovarian carcinoma (FIGO stages III and IV). The end point used in this study was progression-free survival. Immunohistochemistry was performed on microarray blocks containing all 158 cases. Twelve commercially available antibodies were selected. Of them, 10 corresponded to differentially expressed genes in our micro-array study and p53 and Ki67 were included. Antibodies were obtained for the following selected genes: GSTA1, MMP1, FOSB, CTSL2, HSP10, CD36, CXCL2, RBBP7, Siva, and PTGDS. Cox proportional hazards models, adjusted for standard risk factors, were used to estimate the associations between the markers and progression-free survival. No association was found between mRNA level and protein expression by immunohistochemistry. In multivariate analyses, patients whose tumors overexpressed HSP10 had a lower risk of progression than those with low expression (HR: 0.6; CI: 0.42–0.87; P=0.007). High level of proliferation (Ki67) tended to be associated with a lower risk of progression (HR: 0.72; CI: 0.51–1.03; P=0.07) whereas MMP1 overexpression tended to be associated with a higher risk of progression (HR: 1.61; CI: 0.94–2.79; P=0.08). Our study shows that gene expression analysis coupled with immunohistochemistry allowed the identification of HSP10 as an independent factor of progression-free survival.