Expression of the mismatch repair gene hMLH1 is enhanced in non-small cell lung cancer with EGFR mutations

Date

2013-10-24

Authors

Li, Mei
Zhang, Qiuping
Liu, Lina
Lu, Weipeng
Wei, Hong
Li, Rachel W.
Lu, Shen

Journal Title

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Volume Title

Publisher

Public Library of Science

Abstract

Mismatch repair (MMR) plays a pivotal role in keeping the genome stable. MMR dysfunction can lead to carcinogenesis by gene mutation accumulation. HMSH2 and hMLH1 are two key components of MMR. High or low expression of them often mark the status of MMR function. Mutations (EGFR, KRAS, etc) are common in non-small cell lung cancer (NSCLC). However, it is not clear what role MMR plays in NSCLC gene mutations. The expression of MMR proteins hMSH2 and hMLH1, and the proliferation markers PCNA and Ki67 were measured by immunohistochemistry in 181 NSCLCs. EGFR and KRAS mutations were identified by high resolution melting analysis. Stronger hMLH1 expression correlated to a higher frequency of EGFR mutations in exon 19 and 21 (p<0.0005). Overexpression of hMLH1 and the adenocarcinoma subtype were both independent factors that related to EGFR mutations in NSCLCs (p=0.013 and p<0.0005). The expression of hMLH1, hMSH2 and PCNA increased, while Ki67 expression significantly decreased (p=0.030) in NSCLCs with EGFR mutations. Overexpression of hMLH1 could be a new molecular marker to predict the response to EGFR-TKIs in NSCLCs. Furthermore, EGFR mutations might be an early event of NSCLC that occur before MMR dysfunction.

Description

Keywords

adaptor proteins, signal transducing, adenocarcinoma, adult, aged, aged, 80 and over, base pair mismatch, carcinoma, non-small-cell lung, dna mismatch repair, dna repair, exons, female, humans, ki-67 antigen, lung neoplasms, male, middle aged, nuclear proteins, proliferating cell nuclear antigen, proto-oncogene proteins, receptor, epidermal growth factor, ras proteins

Citation

Source

PLoS ONE

Type

Journal article

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DOI

10.1371/journal.pone.0078500

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