NDLI: Promoter methylation and immunohistochemical expression of hMLH1 and hMSH2 in sporadic colorectal cancer: a study from India

Content Provider	Springer Nature Link
Author	Malhotra, Pooja Anwar, Mumtaz Kochhar, Rakesh Ahmad, Shabeer Vaiphei, Kim Mahmood, Safrun
Copyright Year	2013
Abstract	To determine the etiological factors of human colorectal cancer (CRC) we assessed the frequency and prognostic significance of hMLH1 and hMSH2 genes in conjunction with hMLH1 and hMSH2 protein expression in 30 Indian CRC patients. The protein expression and promoter methylation of hMLH1 and hMSH2; Mismatch Repair genes (MMR) were analyzed by immunohistochemistry and methylation-specific PCR (MSP), respectively. A loss of hMLH1 expression was recognized in 4(13.3 %) and loss of hMSH2 expression was recognized in 2(6.6 %) of 30 CRC cases whereas 50 % tumors showed reduced expression of hMLH1 and 33.3 % showed reduced expression of hMSH2 protein. One tumor showed a loss of both hMLH1 and hMSH2 expression. Normal nuclear staining pattern of hMLH1 and hMSH2 was observed in almost all the adjoining and normal mucosa. Promoter hypermethylation of the hMLH1 gene was detected in 15 of 30 CRC cases (50 %) and of hMSH2 gene was only in 3 of 30 CRC cases (10 %). No promoter methylation of hMLH1 and hMSH2 genes was observed in adjoining and normal mucosa. Combination of methylation of hMLH1 and hMSH2 gene was observed in two tumors (6.6 %). A significant correlation between histological grade of the tumor, methylation and expression of hMLH1 gene (p < 0.05) was observed. Normal expression of hMLH1 and hMSH2 was seen in all of the unmethylated tumors (100 %). Nuclear staining and promoter methylation of hMLH1 and hMSH2 did not significantly influence survival. hMLH1 methylation was common and was significantly correlated with loss of hMLH1 protein expression. In contrast, hMSH2 methylation was infrequent. These findings suggest that the inactivation of MMR gene expression probably via hypermethylation may lead to inactivation of their functions which finally leads to tumor aggressiveness and the immunostaining of hMLH1 protein can be used as a prognostic factor for determining the grade of the tumor.
Starting Page	3679
Ending Page	3687
Page Count	9
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	35
Issue Number	4
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-12-10
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Colorectal cancer hMLH1 hMSH2 Methylation Immunohistochemistry Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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