Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research Indan Journal of Medical Research
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ORIGINAL ARTICLE
Year : 2011  |  Volume : 134  |  Issue : 2  |  Page : 186-192

Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma


1 Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang; Advanced Medical & Dental Institute, Universiti Sains Malaysia, Penang, Malaysia
2 Advanced Medical & Dental Institute, Universiti Sains Malaysia, Penang, Malaysia
3 Department of Pathology, Hospital Sultanah Bahiyah, Alor Star, Kedah, Malaysia
4 Department of Internal Medicine, Hospital Sultanah Bahiyah, Alor Star, Kedah, Malaysia
5 Department of Surgery, Hospital Sultanah Bahiyah, Alor Star, Kedah, Malaysia
6 Department of Pathology, Hospital Pulau Pinang, Penang, Malaysia

Correspondence Address:
Gurjeet Kaur
Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Minden, 11800 Penang
Malaysia
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PMID: 21911971

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Background & objectives : DNA mismatch repair gene (MMR) abnormalities are seen in 95 per cent of hereditary nonpolyposis colorectal cancer (HNPCC) and 10-15 per cent of sporadic colorectal cancers. There are no data on MMR abnormalities in Malaysian colorectal cancer patients. This study was aimed to determine the frequency of abnormal MMR gene protein expression in colorectal carcinoma in Northern Peninsular Malaysia using immunohistochemistry. Methods: Clinicopathological information was obtained from 148 patients' records who underwent bowel resection for colorectal cancer (CRC) at the three hospitals in Malaysia. Immunohistochemistry for MLH1, MSH2, MSH6 and PMS2 proteins were performed on paraffin embedded tissue containing carcinoma. Results: A total of 148 subjects and 150 colorectal carcinomas of sporadic and hereditary types were assessed. Three patients had synchronous tumours. Twenty eight cancers (18.6%) from 26 subjects (17.6%) had absent immunohistochemical expression of any one of the MMR gene proteins. This comprised absent MLH1 only - 3 cancers, absent MSH2 only - 3, absent MSH6 only - 2, absent PMS2 only - 3, absent MLH1 and PMS2 - 14, absent MSH2 and MSH6 - 2 and absent MLH1, MSH6 and PMS2 - 1. There was significant association between abnormal MMR gene protein expression and proximal colon cancers, mucinous, signet ring and poorly differentiated morphology. Interpretation & conclusions : Cancers with abnormal MMR gene expression were associated with microsatellite instability-high (MSI-H) phenotype. About 15 per cent demonstrated absent MSH2, MSH6 and PMS2 protein expression in isolation or in combination with other MMR genes, which often predicts a germline mutation, synonymous with a diagnosis of HNPCC. This appears to be high frequency compared to reported data.


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