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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Immunohistochemistry detects mismatch repair gene defects in colorectal cancer
Colorectal Disease, Volume 8, No. 5, Year 2006
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Description
Objective: The clinical management of colorectal malignancies that arise via the mismatch repair gene pathway may differ from those that arise from the more common loss of heterozygosity pathway. They respond differently to chemotherapy, have a different prognosis and are associated with a raised incidence of metachronous lesions if a germline mutation is present. Established methods of detecting mismatch repair gene defects require the testing for microsatellite instability. This is expensive and requires specialized molecular biological resources and staff. An immunohistochemical method is attractive because it is far cheaper, and can be performed by most anatomical pathology laboratories. The aim of this study was to determine the incidence of mismatch repair gene defects using immunohistochemistry in a group of patients who were aged ≤45 years at the time of diagnosis of colorectal cancer and to compare the patient survival and pathological features of tumours with and without mismatch repair gene defects. Methods: One hundred and four patients with colorectal cancer, diagnosed at 45 years or younger between January 1983 and December 2001, who had been managed at Groote Schuur Hospital, were identified from clinical records. Demographic and clinical data was collected from the clinical notes. The pathological reports were reviewed and the original histopathological slides retrieved. New tissue sections were cut from the original paraffin embedded tissue blocks to obtain both normal colonic mucosa and tumour on the same slide. There was insufficient tissue available or poor staining in 11 patients so 93 were available for the study. Results: The mismatch repair status was detected by antibodies to hMLH1 and hMSH2 gene product using a standard immunohistochemical technique. Fifty-six (60%) of 93 tumours demonstrated normal expression of both hMLH1 and hMSH2 protein. Twenty-five (27%) tumours did not express hMLH1 and 12 (13%) hMSH2 proteins. Comparison of the histopathological features revealed that a greater proportion of tumours with absence of either the hMLH1 or hMSH2 product were right sided, mucinous and poorly differentiated when compared to those that expressed the gene product. There was no detectable difference in overall survival or in survival of patients with Duke's C carcinoma when the groups were separated by the presence or absence of gene product. Conclusions: This study found that 40% of patients who were ≤45 years of age at the time of diagnosis of colorectal cancer seen at Groote Schuur Hospital have tumours which are related to the absence of expression of either hMLH1 or hMSH2 genes. © 2006 Blackwell Publishing Ltd.
Authors & Co-Authors
Hameed, F.
South Africa, Cape Town
University of Cape Town
Goldberg, Paul A.
South Africa, Cape Town
University of Cape Town
South Africa, Cape Town
Medical School
Hall, Pauline De La M.
South Africa, Cape Town
University of Cape Town
Algar, Ursula
South Africa, Cape Town
University of Cape Town
van Wijk, Rochelle A.
South Africa, Cape Town
University of Cape Town
Ramesar, Rajkumar S.
South Africa, Cape Town
University of Cape Town
Statistics
Citations: 17
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.1111/j.1463-1318.2006.00956.x
e-ISSN:
14631318
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Study Design
Cohort Study