Date of Award
6-30-2010
Document Type
Dissertation
Degree Name
Master of Medicine (MMed)
First Supervisor/Advisor
S. Sayed
Second Supervisor/Advisor
Z. Moloo
Department
Pathology (East Africa)
Abstract
Introduction: Colorectal cancer is the third most common cancer worldwide, as indicated by WHO. Local published and unpublished data indicate that patients in the developing world with colorectal cancer tend to present at an early age, and possibly at a more advanced stage than described in the developed world. The reason for this difference is unclear, and as yet undefined.
The Wnt/APC pathway, Microsatellite instability pathway and the Epigenetic pathway are three pathogenetically distinct pathways that have been implicated in the development of colorectal cancer. Exploration of these patterns may allow us to elucidate possible reasons for these differences.
Objectives: The aim of this study was to investigate the expression patterns of three molecules, β-catenin, p27 and COX-2, which represent various points of interaction along the Wnt/APC pathway, in colorectal cancers diagnosed at the Department of Pathology,Aga KhanUniversityHospital,Nairobi, and to correlate the findings with clinical, demographic and pathological characteristics of the study subjects.
Methods: Tissue blocks of 100 consecutive colorectal cancer resection specimens received during the period March 2006 to Dec 2009, were retrieved from the archives at the Department of Pathology. Haematoxylin and Eosin slides were prepared and reviewed for purposes of confirmation, typing, grading and staging of the colon cancer. Immunohistochemical expression for β-catenin, p27 and COX-2, was assessed and scored. Findings were correlated with relevant demographic, pathologic and clinical data.
Data Management and analysis: Data were recorded using a data sheet and then entered into an MS Excel spreadsheet. Statistical analysis was done using SPSS version 15.0 (SPSS Inc, Chicago) and STATA version 10.0 (Stata Inc,Texas).
Chi square test (or Fisher’s exact test when number was
Results: β-catenin aberrant expression was found in 75% of tumours. 93% of cases showed moderate to strong nuclear p27 expression and 78% of cases demonstrated moderate to strong COX-2 overexpression. β-catenin expression patterns were associated with tumour location, and COX-2 overexpression with tumour histological subtype.
Conclusion: The aberrant expression of β-catenin corresponds with the overexpression of COX-2, supporting their postulated relationship in the Chromosomal instability pathway.
The Wnt/APC pathway still appears to be the most common pathway, despite our younger population. The utility of p27 still requires further evaluation and validation, due to conflicting results.
Recommended Citation
Okiro, P. (2010). Expression patterns of β–catenin, COX-2 and p27 in colorectal carcinomas at Aga Khan University Hospital, Nairobi (Unpublished master's dissertation). .