Biomarker conservation in primary and metastatic epithelial ovarian cancer

Purpose. The aim of this study was to compare the overexpression of specifi c biomarkers in primary advanced and recurrent epithelial ovarian cancers. Methods. Biomarker expression by epithelial ovarian cancer specimens from p rimary and metastatic sites was examined by immunohistochemistry and flow c ytometry. Biomarker expression by subpopulations of tissues consisting of m atched pairs of synchronous and metachronous lesions was also studied. Results. A total of 3173 epithelial ovarian cancer specimens were retrieved from women with FIGO Stage III/IV disease. These included lesions from 103 6 primary and 2137 metastatic sites. The percentages of biomarker expressio n for primary and metastatic lesions, respectively, were MDR1, 12 and 10%; p53, 55 and 60%; HER2, 12 and 11%; EGF-R, 26 and 33%; increased microvessel counts (CD31), 21 and 36%. Approximately 73% of both primary and metastati c specimens were aneuploid, and approximately 57% of both sets had an S-pha se fraction >7%. Only EGF-R and CD31 expression were found to be significan tly different between the primary and metastatic tumors (P < 0.05). Of the paired synchronous cases (n = 48) evaluated, 88% of aneuploid primary lesio ns were associated with aneuploid metastases. Similarly, the distributions for MDR1, HER2, and p53 expression did not vary significantly between prima ry and metastatic sites. Pairings of metachronous cases (n = 66) revealed t hat nearly 80% of primary aneuploid tumors (n = 39) retained their aneuploi d status at the time of relapse. Furthermore, there were no significant cha nges in MDR1, p53, or HER2 expression at relapse. Conclusions. With the exception of EGFR and CD31, clonal divergence of the biomarkers evaluated in this study probably does not play a significant rol e in imparting clinical heterogeneity during the advanced and recurrent sta ges of epithelial ovarian cancer. These particular genes likely undergo alt erations early in the tumorigenesis process before metastases have become e stablished, (C) 2000 Academic Press.