Assessment of beta-catenin expression by immunohistochemistry in colorectal neoplasms and its role as an additional prognostic marker in colorectal adenocarcinoma

BACKGROUND: Cancer is one of the world’s biggest health care challenges, with colorectal cancer (CRC) being one of the three most frequently encountered malignancy worldwide. The main cause of mortality associated with CRC is tumour invasion and metastasis. Pathogenesis of CRC is a multistep process, during which different molecular pathways come into play. The cardinal genomic alteration that has been found universally present in CRC is a mutation in the adenomatous polyposis coli gene (APC). APC mutation causes unrestricted action of the Wnt signaling pathway which subsequently enhances the intracellular accumulation of a protein called beta-catenin, responsible for cell proliferation, differentiation and enhanced survival of colorectal epithelial cells. AIM: This study was conducted to analyze beta–catenin expression in various colorectal neoplasms, and its change with respect to different grades and stage of colorectal adenocarcinoma. STUDY DESIGN: This was a cross-sectional observational study. METHODS: A total of 66 cases were enrolled in this study. Census method of sampling was used. Data was collected using a pre-designed, pretested semi-structured schedule on dependent variables like beta–catenin expression and independent variables like clinico-pathological profile including dietary history, macroscopic findings, histological type, histological grade, stage and other relevant parameters. An institution based cross sectional observational study was performed between February 2016 and July 2017. Representative sections taken from the specimens included in the study were subjected to histopathological examination followed by immunohistochemistry [IHC] for beta-catenin expression; the data obtained were analyzed by mean ± SD, Student t test, Chi-square/ Fisher Exact test using statistical software SPSS 18.0. RESULTS: A statistically significant correlation (P = 0.004), of beta–catenin localization and IHC score was noted between the benign, premalignant and malignant neoplasms following a gradual transition from a membranous to a nuclear positivity; also, a significant (P<0.001) correlation between beta–catenin nuclear score and the corresponding American Joint Committee on Cancer (AJCC) stage of colorectal adenocarcinoma was also found in this study. CONCLUSION: The purpose of this study was to determine the change in beta-catenin expression which demonstrates a gradual shift from a membranous to subsequent cytoplasmic and nuclear positivity from normal colorectal tissue to benign, premalignant and malignant neoplasms respectively. This property of beta-catenin can determine the malignant potential of various premalignant neoplasms of the large intestine, thus aiding in an early initiation of prophylactic treatment, which can prevent the development of an invasive disease. The membranous, cytoplasmic and nuclear scores show a linear progression with the advancing stages of colorectal carcinoma, making beta–catenin a prognostic marker in malignant colorectal neoplasms.