Title

Expression of mismatch repair proteins in colorectal cancer at Aga Khan University Hospital, Nairobi

Date of Award

2013

Document Type

Dissertation

Degree Name

Master of Medicine (MMed)

First Supervisor/Advisor

Zahir Moloo

Second Supervisor/Advisor

Shaheen Sayed

Department

Pathology (East Africa)

Abstract

Introduction: Microsatellite instability is one of three molecular pathways described in the pathogenesis of colorectal carcinoma. The presence of microsatellite instability in patients with colorectal cancer has implications for prognosis and family counselling. Deficiency in mismatch repair genes leads to microsatellite instability and this can be reliably demonstrated in formalin fixed paraffin embedded tissue by methods, which include immunohistochemistry for the detection of mismatch repair proteins.

Local data show a disproportionately large number of younger patients with colorectal cancer compared to that documented in Caucasians. Colorectal cancer in younger ages is often attributed to deficient mismatch repair.

The objective of this study therefore, was to determine the proportion of colorectal cancers associated with the microsatellite instability pathway through detection of the mismatch repair proteins on immunohistochemistry.

Materials and Methods: This was a retrospective study of 80 colorectal adenocarcinoma resection specimens received over a three-year period from January 2009 to January 2012. The mismatch repair gene mutation expression was analysed by immunohistochemical staining for products of mismatch repair genes. Associated clinical and pathologic characteristics were reviewed and documented.

Results: The proportion of deficient mismatch colorectal cancer in the study was 19.4% [95% CI 11.7%-30.4%].There was a significant but weak association between mismatch repair gene protein expression and tumour grade, and tumour infiltrating lymphocytes (tumour grade Cramer’s V=0.263, p=0.031; tumour infiltrating lymphocytes Cramer’s V=0.246, p=0.044). Mismatch repair gene protein expression outcome showed significant but moderately strong association with the anatomic site of tumour, and tumour histological type (anatomic site Cramer’s V=0.469, p=0.001, tumour histological type Cramer’s V=0.469, p=0.001,).

Conclusions: The study provides preliminary data of the contribution of the deficient mismatch repair molecular pathway of colorectal cancer in Kenya.

This document is available in the relevant AKU library

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