Nuclear Localisation of Autophagic p62 and Associated Cytoplasmic Beclin-1 and Bcl-2 Expressions in Adenomas and Adenocarcinomas of the Colorectal Regions

Abstract

Background: Autophagy is an important biological process that is involved in cellular homeostasis and survival. Derailment of some cellular autophagic processes affects normal cellular function, resulting in cancers and other disorders. Autophagy related proteins are Beclin-1, a human tumour suppressor, Bcl-2 and p62 have been characterised in most cancers. Particularly, a number of studies have reported a loss of Beclin-1 and up regulation of Bcl-2 and p62 in breast cancers. However, studies regarding the expression of these proteins in colorectal adenomaadenocarcinoma transformation sequence are yet to be described. In this study, we examined the expression patterns of Beclin-1, Bcl-2 and p62 in both colorectal adenomas and adenocarcinomas. Methods: Immunohistochemistry was performed on formalin-fixed paraffin embedded tissue sections from 14 patients with colorectal tumours and the expression patterns were semi-quantitatively evaluated based on the intensity of staining and the percentage of tumour cells stained. Results: Cytoplasmic Beclin-1 and p62 expression patterns ranged from moderate to high in both tubular adenomas and adenocarcinomas as compared to normal colonic mucosa. Cytoplasmic Bcl-2 expression was moderately expressed in tubular adenomas but negative to low expression was observed in the adenocarcinomas. This study also provided, for the first time, nuclear localization of p62 in only the colorectal adenocarcinomas. Conclusion: Beclin-1, Bcl-2 and p62 may be up regulated in the transition of colorectal adenomas to adenocarcinomas.