Abstract

Abstract Mini-Chromosome Maintenance protein 7 (MCM7) is involved in replicative licensing and synthesis of DNA. It is previously identified as over-expressed gene in high-grade serous carcinomas compared to serous borderline tumors of the ovary in cDNA microarray studies. In this study, we sought to validate MCM7 expression in ovarian tumors by applying immunohistochemical analysis on tissue microarrays consisting of 445 ovarian tumors. MCM7 expression was quantified as MCM7 labeling index by determining the tumor nuclei positive for MCM7 staining as a percentage of total tumor nuclei. The labeling index scores were independently generated by two methods: PATH score provided by a manual review of each samples by a pathologist and ACIS score provided by Automated Cell Imaging System. Analyses of both scores indicated high degree of concordance in score distribution between PATH and ACIS. MCM7 expression is significantly higher in high-grade serous carcinomas compared to serous borderline tumors, confirming our previous cDNA microarray studies. In both PATH and ACIS analysis, MCM7 expression is also significantly higher in high-grade serous carcinomas compared to other histology subtypes of ovarian cancer. Finally, to identify the clinical significance of MCM7 expression, we determined the association between MCM7 expression and disease-free survival. MCM7 labeling index was dichotomized into two groups (high and low) using median labeling index as cut-off. For both PATH or ACIS-derived scores, univariate analyses indicate significant association of high MCM7 labeling index with better disease-free survival in high-grade serous carcinomas. These results suggest the clinical significance of MCM7 expression in high-grade serous carcinomas of the ovary and the need for further evaluation of MCM7 as a potential theranostic biomarker. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4637.

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