High Beclin 1 expression defines a poor prognosis in endometrial adenocarcinomas

ObjectiveTo investigate the prognostic role of Beclin 1 in endometrial adenocarcinomas of the endometrioid cell type. Beclin 1 is a known tumor suppressor gene, but its function may be altered under conditions of an accelerated autophagic activity, which provides additional energy to proliferating cells by recycling defective organelles and long-lived cytoplasmic proteins.Materials and methodsOne hundred and fifty-five endometrioid adenocarcinomas were investigated for their autophagic activity using the monoclonal antibody Beclin 1 and an automated immunohistochemical technique. The extent of Beclin 1 expression was evaluated on a three-tier scale as follows: low (< 10% positive tumor cells), intermediate (between 10% and 50% positive tumor cells), and high (> 50% positive tumor cells). The results were correlated with the degree of tumor differentiation, the depth of myometrial invasion and the overall 5-year survival. In addition, the endometrial tumors were immunostained with the hypoxia inducible factor 1α (HIF1α) and their expression was related to Beclin 1.ResultsA high Beclin 1 reactivity occurred in 18.1% of endometrial adenocarcinomas studied and was associated with high tumor grade, high myometrial invasion and a poor 5-year survival. It was also correlated positively with HIF1α. Of the remaining adenocarcinomas 29.7% were of intermediate Beclin 1 reactivity and 52.2% of low, but correlations with prognostic factors were insignificant.ConclusionAn increased Beclin 1 expression is connected with the most aggressive endometrioid adenocarcinomas, probably as a result of its strong association with tumor hypoxia.

► Beclin 1, a marker of autophagic activity, was highly expressed in 18% of endometrioid adenocarcinomas and down-regulated in 52%. ► A high Beclin 1 expression was associated with high tumor grade, deep myometrial invasion and a poor 5-year survival. ► HIF1α and Beclin 1 proteins were significantly co-expressed, suggesting a link between beclin 1 expression and intratumoral hypoxia.