title: High Beclin 1 expression defines a poor prognosis in endometrial adenocarcinomas.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  One 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.
  
  
  RESULTS
  A 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.
  
  
  CONCLUSIONS
  An increased Beclin 1 expression is connected with the most aggressive endometrioid adenocarcinomas, probably as a result of its strong association with tumor hypoxia.
authors: Department of Pathology, Democritus University of Thrace Medical School, and University General Hospital of Alexandroupolis, Alexandroupolis, Greece. agiatrom@med.duth.gr
authors: Alexandra
authors: A
authors: Giatromanolaki
authors: Michael I
authors: MI
authors: Koukourakis
authors: Anastasios
authors: A
authors: Koutsopoulos
authors: Pelagia
authors: P
authors: Chloropoulou
authors: Vasileios
authors: V
authors: Liberis
authors: Efthimios
authors: E
authors: Sivridis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D000071186:Beclin-1; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018269:Carcinoma, Endometrioid / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D014408:Biomarkers, Tumor; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008565:Membrane Proteins