MGST1 expression in serous ovarian carcinoma differs at various anatomic sites, but is unrelated to chemoresistance or survival

Abstract

Objective: To investigate the expression of MGST1 in primary tumors, solid metastases and metastatic effusions in advanced-stage serous ovarian carcinoma (OC) and analyze the association with clinicopathologic parameters, including chemotherapy resistance and survival.

Methods: MGST1 mRNA expression was investigated in 178 tumors (88 effusions, 38 primary carcinomas, 52 solid metastases) from 144 patients using real-time quantitative PCR (qRT-PCR). Forty-two of the 88 effusions were additionally analyzed for MGST1 protein expression by Western blotting.

Results: mRNA expression of MGST1 was higher in primary carcinomas and solid metastases compared to effusions (p=0.008 and p=0.012, respectively). In patient-matched samples, mRNA expression of MGST1 was higher in solid metastases compared to effusions (p=0.023), and a trend for higher MGST1 levels in solid metastases compared to primary tumors was observed (p=0.06). Biopsies from primary carcinomas obtained from patients with >200 ml ascites at diagnosis had higher mRNA expression of MGST1 compared to samples from patients with <200 ml ascites (p=0.037). MGST1 mRNA expression was not associated with age, histological grade, tumor stage, residual disease volume, response to chemotherapy, chemotherapy resistance or survival. Western blot analysis of patient-matched effusions showed high concordance between MGST1 protein and mRNA levels measured by qRT-PCR (p<0.001).

Conclusions: The present study documents frequent MGST1 mRNA and protein expression in OC. The data suggest increased activity of oxidative response pathways, reflected by higher mRNA expression, in solid OC tumors compared to metastatic effusions. Additionally, a tumor microenvironment consisting of ascites may induce antioxidant activity.