Expression of beclin-1, an autophagy-related protein, in stage III B colon cancer and its relationship with prognosis

Objective:Autophagy is a form of eukaryotic cell death by which the cell recycles its components through self-consumption of cellular organelles and bulk cytoplasm using hydrolytic enzymes stored in lysosomes.The role of autophagy in carcinogenesis and tumor progression is elusive.Beclin-1,a key regulator of autophagy in mammals,has been considered a haploinsufficient tumor suppressor.This study investigates the expression of beclin-1 in stage ⅢB human colon cancer and analyzes the association of beclin-1 expression with clinocopathologic characteristics and prognosis.Methods:A total of 115 cases of colon cancer specimens were obtained from radically resected stage Ⅲ B colon cancer tumors between January 1999 and July 2003 with complete follow-up data in our center.Tissue arrays were constructed from formalin-fixed and paraffin-embedded tissues.The expression of beclin-1 in tumor tissue and adjacent normal tissue was examined with immunohistochemistry.The relationship between beclin-1 expression and clinicopathological parameters was analyzed.Results:Expression of beclin-1 was observed in the plasma membrane,cytoplasm and nucleus in tumor cells.In the tumor tissues analyzed,immunopositivity was observed for beclin-1 in 98(85.2%) of the 115 tumor tissues.In contrast,adjacent non-cancerous tissues and normal tissues showed no or very weak expression of beclin-1.The 5-year overall survival rate for beclin-1 immunopositive cases was 67.3% and for beclin-1 immunonegative cases the rate was 47.1%.The 5-year overall survival rate was 68.9% for T3N0M0 cases and 25.0% for T4N0M0 cases.There was a significant association of beclin-1 expression and T stage with 5-year overall survival rate.No significant correlation was found between beclin-1 expression and clinocopathologic characteristics including sex,age,tumor site,pathologic type,grade,and invasive depth(T stage).Both univariate analysis and multivariate analysis showed that beclin-1 and T stage were independent prognostic factors.Conclusion:Beclin-1 plays an important role in the regulation of the life span of human colon cells by maintaining autophagy at levels promoting cell death rather than cell survival.In locally advanced colon carcinomas,tumor cells with the potential for autophagy fail to survive.Alternatively,a deficiency in autophagy may be involved in tumor progression.Further research is warranted to elucidate the detailed mechanism.