title: Deficiency of MSH2 expression is associated with clear cell renal cell carcinoma.
abstract: DNA hypermethylation plays a major role in the regulation of gene expression in differentiation, development and diseases. The DNA mismatch repair system, which includes Mut-S-Homologon-2 (MSH2) protein, is essential to maintain the stability of the genome during repeated duplication. This study aimed to investigate tumoral MSH2 immunohistochemical expression in clear cell renal cell carcinoma (RCC), and the associations between tumoral MSH2 immunohistochemical expression and clinicopathological parameters. Previously, we reported a high-throughput method for analyzing the methylation status of 807 preselected genes; Illumina's GoldenGate Methylation Cancer Panel I microarray. The MSH2 gene was identified to be hypermethylated in cancer tissue compared with normal tissue. From January 2000 to December 2012, 129 clear cell RCC cases (median age, 61 years) were included in the immunohistochemical analysis of the present study. Patients were divided according to MSH2 expression status (MSH2-negative, n=53; MSH2-positive, n=76). T stage was significantly higher in the MSH2-negative group than in the MSH2 positive-group (P=0.021). There was no significant difference in terms of N stage, M stage and Fuhrman's nuclear grade between the MSH2-negative and MSH2-positive group (N stage, P=0.072; M stage, P=0.759; Fuhrman's nuclear grade, P=0118). The MSH2-negative group showed decreased rates of recurrence-free survival, progression-free survival and overall survival, without statistically significant results (P=0.232, P=0.268 and P=0.311, respectively). MSH2 protein expression may be a useful marker for predicting TNM stage and prognosis and, thus, MSH2 may be a prognostic factor in clear cell RCC.
authors.affiliation: Department of Urology, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors.forename: Koo Han
authors.initials: KH
authors.lastname: Yoo
authors.affiliation: Department of Pathology, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors.forename: Kyu Yeoun
authors.initials: KY
authors.lastname: Won
authors.affiliation: Department of Pathology, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors.forename: Sung-Jig
authors.initials: SJ
authors.lastname: Lim
authors.affiliation: Department of Pathology, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors.forename: Yong-Koo
authors.initials: YK
authors.lastname: Park
authors.affiliation: Department of Urology, School of Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.
authors.forename: Sung-Goo
authors.initials: SG
authors.lastname: Chang
keywords: DNA methylation; MSH2 protein; immunohistochemistry; renal cell carcinoma