Subcellular Localization of Beta Catenin in Colorectal Non Neoplastic and Neoplastic Lesions

Loss of adenomatous polyposis coli (APC) function is typically an early event  in sporadic colorectal cancer (CRC) pathogenesis. The key tumor suppressor function of the APC  protein lies in its ability to destabilize free cytoplasmic beta catenin. This lead to the accumulation of nuclear beta catenin, and together with the DNA binding protein Tcf-4, function as a transcriptional activator. Accumulation of stabilized free  β-catenin is considered as an early event and perhaps initiating the process in intestinal tumorigenesis. Neoplastic transformation in the CRC associated chronic colitis is considered similar to the adenoma-carcinoma sequence in sporadic CRC. The distinguish feature from the CRC-related colitis is the difference in time and frequency changes. Loss of APC function, regarded as the beginning of a very common event in sporadic CRC, but the CRC associated chronic colitis generally occurs at the end of the dysplasia-carcinoma sequence. This research was conducted to determine the subcellular location of beta catenin expression in chronic colitis, colorectal adenomas and carcinomas that were evaluated by immunohistochemical staining. It can be concluded that beta-catenin is a component that plays a role in the development of the CRC and the subcellular location of beta-catenin can describe its oncogenic activity.&nbsp

Alteration of Subcellular Beta Catenin Expression in Normal Mucosa Adenoma and Carcinoma in Relation to Colorectal Carcinogenesis

Background: Adenomatous polyposis coli (APC) gene mutation was found in up to 80% of cases of sporadic colorectal cancers and adenomas. Loss of APC protein function has been known as one of the early process in colorectal carcinogenesis. This event leads to the accumulation of beta catenin in the cytoplasm and nucleus and subsequently activates target genes that regulate cell proliferation and apoptosis. The aim of this study was to investigate the alteration of subcellular beta catenin expression in the progression of colorectal cancer. Method: This cross-sectional study was conducted with 30 paraffin-embedded tissue sections each of normal colorectal mucosa, adenomas and carcinomas. Alteration of beta catenin expression in membranous, cytoplasmic, and nuclear compartments were evaluated by immunohistochemical staining. Results: Beta catenin immunoreactivity was detected in all cases, of which 87 (96.7%) cases showed membranous expression, 78 (86.7%) cases had cytoplasmic and 51 cases (56.7%) had nuclear expression. Such results were statistically significant (p < 0.000). All normal colorectal epithelium showed membranous beta catenin expression with 18 (60.0%) cases showed cytoplasmic and no nuclear beta catenin expression was found. Strong cytoplasmic expression was found in 17 (56.7%) adenomas and 25 (83.3%) carcinomas; while strong nuclear expression was found in 12 (40.0%) adenomas and 17 (56.7%) carcinomas. There was no statistical significant association between beta catenin expression in the membranous, cytoplasmic and nuclear compartment with the degree of dysplasia or differentiation of tumor (p > 0.05). Conclusion: Altered subcellular expression of beta catenin occurs as the oncogenic process develops from adenoma into carcinoma. Such finding reflects the importance of beta-catenin in colorectal carcinogenesis