title: Expression of the mismatch repair gene hMLH1 is enhanced in non-small cell lung cancer with EGFR mutations.
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.
authors.affiliation: Central Laboratory, The Second Hospital of Dalian Medical University, Dalian, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Zhang
authors.forename: Lina
authors.initials: L
authors.lastname: Liu
authors.forename: Weipeng
authors.initials: W
authors.lastname: Lu
authors.forename: Hong
authors.initials: H
authors.lastname: Wei
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Li
authors.forename: Shen
authors.initials: S
authors.lastname: Lu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020137:Base Pair Mismatch / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C117307:KRAS protein, human; D019394:Ki-67 Antigen; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D000070957:MutL Protein Homolog 1; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins