Volume 11, Number 2, August 2010 83 O RIG INAL ARTIC LE INTRODUCTION Colorectal carcinoma (CRC) is the third major malignancy worldwide after lung cancer and breast cancer and it is the third leading cause of cancer death from all cancers. 1 Until now, the curative treatment is surgical resection although adjuvant treatment has been growing rapidly. However, there is little that can improve the survival rate of patients in advanced stages Alteration of Subcellular Beta Catenin Expression in Normal Mucosa, Adenoma and Carcinoma in Relation to Colorectal Carcinogenesis Pamela Damaledo Abineno, Diah Rini Handjari, Budiningsih Siregar Department of Anatomical Pathology, Faculty of Medicine, University of Indonesia Dr. Cipto Mangunkusumo General National Hospital, Jakarta ABSTRACT 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. Keywords: beta catenin, colorectal cancer, adenoma, colorectal cancer progression of the CRC. 2 The detection of new cases in the early stages should be developed as a preventive action that can reduce morbidity and mortality in CRC patients. 3 Colorectal carcinogenesis is a multistep processes that occurs due to genetic changes from normal mucosa to adenoma and then carcinoma. This pathway requires the accumulation of genetic changes which proceeded by the inactivation of tumor suppressor gene adenomatous polyposis coli (APC). 4 Beta catenin has recently been the object of increasing interest because of the discovery of additional functions of this protein apart from its well-known role in cell adhesion. 5 The implication of beta catenin in the transduction of Wingless/Wnt-dependent cell–cell signaling has been demonstrated. 6 Furthermore, beta catenin may also Correspondence: Diah Rini Handjari Department of Anatomical Pathology Dr. Cipto Mangunkusumo General National Hospital Jl. Diponegoro No. 71 Jakarta 10430 Indonesia Phone: +62-21-31905888 Fax: +62-21-31934465 E-mail: rinidiah@gmail.com