Expression Pattern of APC And P53 Proteins in Left-Sided and Right-Sided Colorectal Cancer in Ghanaians

Abstract

Background: The development of colorectal cancer tumours is significantly impacted by the loss of APC and p53 protein function. The anatomical difference between the left and right colon, significantly influence tumorigenesis of left-sided and right-sided colorectal cancers. Additionally, because of genetic and environmental differences, there are variations in how APC and p53 affect the tumorigenesis of left- and right-sided colorectal cancer in different racial groups. Differences in the genetic characterization of left-sided and right-sided colorectal cancers has informed the use of tailor-made treatment that has contributed to increased survival rate in the developed countries. Aim: This study aimed to determine the expression pattern of APC and p53 proteins in left and right-sided colorectal cancer in Ghanaians and compare results to expression pattern of APC and p53 in left and right normal colon. Methodology: Ninety formalin-fixed paraffin-embedded blocks were subjected to semi automated immunohistochemistry staining to determine the pattern of APC and p53 protein expression in left-sided and right-sided colorectal cancers. Two independent assessors scored the expression levels of the APC and p53 proteins in colorectal cancer and healthy colon tissues independently, and Cohen's Kappa was used to determine the inter-rater reliability of the results. To determine the significance of these proteins in the development and progression of colorectal cancer in Ghanaians, the expression of the APC and p53 proteins in left-sided and right-sided colorectal cancer were compared to the controls. Result: APC protein was found in 74.4% of the total number of colorectal cancer cases and 100% of normal colons, with a p-value of 0.012. Protein p53 was found in 73.3% of colorectal cancers compared to 94.7% of normal colon (p-value = 0.044). APC protein expression was found in 70% of left-sided colorectal cancer and 100% of left normal colon. APC protein expression was found in 86.7% of right-sided colorectal cancers and 100% of right normal colon. The p53 protein was expressed in 75% of left-sided colorectal cancers and 100% of left normal colons. Protein p53 expression was found in 70% of right-sided colorectal cancers and 87.5% of right normal colons. With a p-value of 0.001, high p53 expression was significantly associated with LCRCs versus RCRCs. There was no correlation between protein expression and tumour stage or grade. Conclusion: The significant difference in APC expression between healthy and cancerous colons demonstrates that loss of APC expression influences the development of colorectal cancer in a small percentage of Ghanaians. The high proportion of APC protein expression in both left-sided and right-sided colorectal cancers may demonstrate the majority of colorectal cancers in Ghanaians are not caused by loss of expression of wild type APC protein, and that other molecular genetic factors contribute to the initiation of colorectal cancer in Ghanaians.