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. 2014 Nov;8(5):2135-2139.
doi: 10.3892/ol.2014.2482. Epub 2014 Aug 26.

Deficiency of MSH2 expression is associated with clear cell renal cell carcinoma

Koo Han Yoo  1 , Kyu Yeoun Won  2 , Sung-Jig Lim  2 , Yong-Koo Park  2 , Sung-Goo Chang  1
Affiliations

Deficiency of MSH2 expression is associated with clear cell renal cell carcinoma

Koo Han Yoo et al. Oncol Lett. 2014 Nov.

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.

Keywords: DNA methylation; MSH2 protein; immunohistochemistry; renal cell carcinoma.

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Figures

Figure 1
Figure 1
Tissue microarrays using clear cell RCC and normal kidney tissue. (A) Diffusely strong positive expression of MSH2 in clear cell RCC tissues at low magnification (x20). (B) Negative expression of MSH2 in clear cell RCC tissues at low magnification (x20). (C) Normal kidney cells show diffusely strong MSH2 expression at low magnification (x20). (D) RCC cells show diffusely strong nuclear MSH2 expression (magnification, ×200). (E) RCC cells show focally weak nuclear MSH2 expression (magnification, ×200). (F) MSH2 protein is expressed in the nuclei of tubular epithelial cells and parietal cells of Bowman’s capsule (magnification, ×100). RCC, renal cell carcinoma.
Figure 2
Figure 2
(A) Recurrence-free survival, (B) progression-free survival and (C) overall survival of the 129 clear cell renal cell carcinoma patients were analyzed according to the degree of expression by immunohistochemistry.
See this image and copyright information in PMC

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