DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers

Abstract

Objective: Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study.

Methods: A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively.

Results: Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers.

Conclusion: MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.

Keywords: Biological Markers; Carcinogenesis; DNA Mismatch Repair; Endometrial Neoplasms; Multivariate Analysis; Retrospective Studies.

Fig. 1

Kaplan-Meier survival curves of all cases according to mismatch repair (MMR) status. (A) Progression-free survival (PFS) curve of MMR-retained cases (dotted line) and MMR-deficient cases (solid line). Five-year PFS was 92% in MMR-deficient patients, and 78% in MMR-retained patients (p=0.013). (B) Overall survival (OS) curves of MMR-retained cases (dotted line) and MMR-deficient cases (solid line). Five-year OS was 94% in MMR-deficient patients, and 78% in MMR-retained patients (p=0.009).