Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma
نویسندگان
چکیده
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.
منابع مشابه
Deficient mismatch repair and RAS mutation in colorectal carcinoma patients: a retrospective study in Eastern China
Objectives To investigate the frequency and prognostic role of deficient mismatch repair (dMMR) and RAS mutation in Chinese patients with colorectal carcinoma. Methods Clinical and pathological information from 813 patients were reviewed and recorded. Expression of mismatch repair proteins was tested by immunohistochemistry. Mutation analyses for RAS gene were performed by real-time polymeras...
متن کاملDNA Mismatch Repair Deficiency in Colorectal Adenocarcinoma and its Association with Clinicopathological Features
Background: Evaluation of mismatch repair (MMR) status in colorectal cancer (CRC) could be used as the guidance for postsurgical treatment. Defective MMR status is associated with distinct clinicopathological features. This study aims to evaluate associations between MMR status and clinicopathological features in a retrospective cohort of consecutive Chinese CRC patients. Methods: Clinicopathol...
متن کاملسه موتاسیون ژرم لاین جدید در ژن MLH1 در بیماران مبتلا به سرطان کولورکتال ارثی
Abstract Background: Hereditary non-polyposis colorectal cancer is the most common cause of early onset of hereditary colorectal cancer. In the majority of Hereditary non-polyposis colorectal cancer families, microsatellite instability and germline mutation in one of the DNA mismatch repair genes in clouding MSH2, MLH1, MSH6 and PMS2 are found. The Objective of this study was to determine th...
متن کاملClinicopathological Characteristics and Prognosis of Colorectal Cancer in Chinese Adolescent Patients.
BACKGROUND Colorectal adenocarcinoma rarely occurred in adolescent. Clinical feature and prognosis of this population are not clear until now. In addition, DNA mismatch repair (MMR) status may relate to the early disease occurrence. The present study aimed to perform a retrospective analysis of adolescent patients with colorectal cancer, including clinicopathological characteristics and prognos...
متن کاملSystematic immunohistochemical screening for mismatch repair and ERCC1 gene expression from colorectal cancers in China: Clinicopathological characteristics and effects on survival
BACKGROUND We performed a systematic screening of colorectal cancer (CRC) tissues to investigate whether mismatch repair (MMR) status and ERCC1 protein expression could be predictive of clinical outcomes for these patients following the recommendation of The Evaluation of Genomic Applications in Practice of Prevention (EGAPP). METHODS The expression of four MMR genes and ERCC1 were assessed b...
متن کامل