hMLH1/hMSH2 Protein Expression in Sporadic Colorectal Carcinoma and Its Clinicopathological Significance.
- Author:
Jae Hee KANG
1
;
Kil Yeon LEE
;
Kee Hyung LEE
;
Choong YOON
;
Soo Myung OH
;
Joo Hee LEE
Author Information
1. Department of Surgery, Kyung-Hee University Hospital, Seoul, Korea. keehlee@chollian.net
- Publication Type:Original Article
- Keywords:
Sporadic colorectal cancer;
hMLH1;
hMSH2;
Microsatellite instability;
Immunohistochemistry
- MeSH:
Antibodies, Monoclonal;
Base Sequence;
Colorectal Neoplasms*;
Colorectal Neoplasms, Hereditary Nonpolyposis;
DNA Mismatch Repair;
DNA Replication;
Formaldehyde;
Humans;
Immunohistochemistry;
Mass Screening;
Microsatellite Instability;
Mucins;
Paraffin;
Prognosis
- From:Journal of the Korean Society of Coloproctology
2001;17(1):38-46
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: DNA replication errors (RERs) in repeated nucleotide sequences (microsatellite instability) is caused by defective mismatch repair (MMR) genes. Ninety percent of colorectal carcinomas in hereditary nonpolyposis colorectal cancer (HNPCC) patients and 10-15% of sporadic colorectal cancers show microsatellite instability. In the majority of colorectal cancers with microsatellite instability, the defective MMR gene is hMLH1 or hMSH2. The author examined immunohistochemical expression of hMLH1 and hMSH2 in 75 cases of colorectal carcinomas excluding HNPCC, based on Amsterdam criteria for investigating clinicopathological characteristics and prognosis in hMLH1/hMSH2 negative cases. METHODS: Formalin fixed, paraffin blocks obtained from tumors of 75 cases of colorectal cancers were stained with two monoclonal antibodies (hMLH1 and hMSH2). The correlation between hMLH1/hMSH2 negativity, and clinicopathological feature and prognosis were statistically analysed. RESULTS: Twelve cases (16.0%) showed hMLH1/hMSH2 negativity. Negative expression of hMLH1/hMSH2 was associated with early onset (under age 50), proximal location, multiplicity, mucinous histologic type and poor differentiation. There was a significant survival advantage in patients with hMLH1/hMSH2 negative colorectal carcinoma. CONCLUSIONS: This study shows that hMLH1/hMSH2 negative colorectal carcinomas have the same clinicopathological characteristics of colorectal carcinomas with microsatellite instability. The immunohistochemical test for hMLH1/hMSH2 protein can be a simple screening method routinely applicable. The result of this test is available for establishing guidelines for management, and an independent prognostic factor for sporadic colorectal cancers.
