Biomarker Conservation in Primary and Metastatic Epithelial Ovarian Cancer

Abstract

Purpose. The aim of this study was to compare the overexpression of specific biomarkers in primary advanced and recurrent epithelial ovarian cancers.Methods. Biomarker expression by epithelial ovarian cancer specimens from primary and metastatic sites was examined by immunohistochemistry and flow cytometry. Biomarker expression by subpopulations of tissues consisting of matched 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 1036 primary and 2137 metastatic sites. The percentages of biomarker expression 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 metastatic specimens were aneuploid, and approximately 57% of both sets had an S-phase fraction >7%. Only EGF-R and CD31 expression were found to be significantly different between the primary and metastatic tumors (P < 0.05). Of the paired synchronous cases (n ‫؍‬ 48) evaluated, 88% of aneuploid primary lesions were associated with aneuploid metastases. Similarly, the distributions for MDR1, HER2, and p53 expression did not vary significantly between primary and metastatic sites. Pairings of metachronous cases (n ‫؍‬ 66) revealed that nearly 80% of primary aneuploid tumors (n ‫؍‬ 39) retained their aneuploid status at the time of relapse. Furthermore, there were no significant changes in MDR1, p53, or HER2 expression at relapse.Conclusions. With the exception of EGF-R and CD31, clonal divergence of the biomarkers evaluated in this study probably does not play a significant role in imparting clinical heterogeneity during the advanced and recurrent stages of epithelial ovarian cancer. These particular genes likely undergo alterations early in the tumorigenesis process before metastases have become established.

Comparison of clinical staging of benign and malignant ovarian tissues with DNA flow cytometry

“…This data study suggest that aneuploidy if ever demonstrated in histologically confirmed borderline tumors should prompt more sampling of the tumor and a close follow up. Similar results have been seen in by other studies [53][54][55][56] . Lai et al [55] found that reproducible DNA aneuploidy of high DI may be predicting a poor outcome in 50 borderline ovarian cases.…”

HER-2 - A Possible Target for Therapy of Metastatic Urinary Bladder Carcinoma

“…All metastases were either homogeneously positive or negative. Tewari et al (32) found that H ER -2 was expressed in 11% of metastases from epithelial ovarian cancer (n ¾ 1444) and in 12% of primary tumours (n ¾ 730). H ER -2 expression did not signi cantly differ in primary and metastatic sites from the same patient (n ¾ 38).…”

A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors

“…19,20,[23][24][25]28,29,39,42,46,[49][50][51]53,58,[61][62][63][64]66,[71][72][73][74][76][77][78][79]82,83,85,87,90,95,97,99,103,104,106,109,110,114 Overall, p53 was detected in 39% of the Stage I/II tumors and 55% of the Stage III/IV tumors ( Again, although antibody specific estimates by tumor grade varied considerably (data not shown), a consistent pattern emerged. Overall, the proportion of tumors positive for p53 was lowest among the Grade 1 tumors and highest among the Grade 3 tumors (Fig.…”