Beclin 1 over- and underexpression in colorectal cancer: distinct patterns relate to prognosis and tumour hypoxia.

Journal article

INTRODUCTION: Autophagy enables cells to recycle long-lived proteins or damaged organelles. Beclin 1, the mammalian orthologue of the yeast Apg6/Vps30 gene, functions as a scaffold for the formation of autophagosomes. MATERIALS AND METHOD: The immunohistochemical patterns of Beclin 1 expression and their prognostic relevance were studied in formalin-fixed tissues from 155 patients with colorectal adenocarcinoma treated with surgery alone. RESULTS: Using the weak homogeneous expression of Beclin 1 in normal colonic tissues as a basis for assessing tumours, the following grouping/staining patterns were recognised in colorectal carcinomas: a normal-like pattern in 62 of 155 (40%) cases, an underexpression pattern in 24 of 155 (15.5%) cases, extensive overexpression of Beclin 1 in 33 of 155 (21.3%) tumours and limited overexpression of the protein in 36 of 155 (23.2%) tumours. Extensive overexpression of Beclin 1 was significantly linked with overexpression of HIF1α and LDH5, as well as with high histological grade, vascular invasion and nodal involvement. Furthermore, patients with extensive over- or underexpression of Beclin 1 had a significantly poorer overall survival compared with the other two groups (P<0.0001). Beclin 1 had an independent prognostic relevance in multivariate analysis. CONCLUSIONS: Beclin 1 has an important role in growth and metastasis of colorectal cancer. Loss of Beclin 1 expression (allelic loss or microRNA regulatory activity, as suggested in the literature) defines poor prognosis presumably by promoting anti-apoptotic pathways, while overexpression of the protein, being linked with tumour hypoxia and acidity, also defines subgroups of tumours with aggressive clinical behaviour.

Authors: Koukourakis, M; Giatromanolaki, A; Sivridis, E; Pitiakoudis, M; Gatter, K

• Publication status: Published
• Journal: British journal of cancer
• Volume: 103
• Issue: 8
• Pages: 1209-1214
• Publication date: 2010-10-01
• DOI: 10.1038/sj.bjc.6605904
• EISSN: 1532-1827
• ISSN: 0007-0920
• Language: English
• Keywords: Survival Analysis; Female; Cell Hypoxia; Down-Regulation; Retrospective Studies; Necrosis; Adenocarcinoma; Membrane Proteins; Colorectal Neoplasms; Apoptosis Regulatory Proteins; Middle Aged; Adult; Male; Hydrogen-Ion Concentration; Aged; Up-Regulation; Humans; Prognosis; Aged, 80 and over