Expression of Beclin 1 and Bcl-2 in pancreatic neoplasms and its effect on pancreatic ductal adenocarcinoma prognosis

Oncol Lett. 2017 Dec;14(6):7849-7861. doi: 10.3892/ol.2017.7218. Epub 2017 Oct 18.

Abstract

Aberrant expression of Beclin 1 and B-cell lymphoma-2 (Bcl-2) has been identified in a variety of human tumors; however, little information is available for pancreatic neoplasms. The present study analyzed the expression of Beclin 1 and Bcl-2 in pancreatic ductal adenocarcinoma (PDAC) and solid pseudopapillary neoplasm (SPN) of the pancreas, and evaluated their prognostic significance for PDAC. The present study included 117 PDAC, 43 SPN and 32 chronic pancreatitis (CP) cases. Levels of Beclin 1 and Bcl-2 expression were evaluated semiquantitatively by immunohistochemistry, and their correlation with the survival of patients with PDAC was determined. Beclin 1 was upregulated in 74 (63.2%) PDAC, 26 (60.5%) SPN, and 14 (43.8%) CP cases. Bcl-2 was upregulated in 38 (32.5%) PDAC, 11 (25.6%) SPN and 24 (75.0%) CP cases. High Beclin 1 and low Bcl-2 expression was significantly correlated with poor differentiation and distant metastasis in PDAC, and associated with the presence of nuclear pleomorphism in SPN and with advanced Tumor-Node-Metastasis stage in PDAC. Beclin 1 and Bcl-2 levels were inversely correlated in PDAC, whereas they were positively correlated in SPN. Low Beclin 1 and high Bcl-2 expression was associated with improved disease-free survival and overall survival (OS). However, the association of Beclin 1 with survival was not significant in the Cox analysis, whereas Bcl-2 expression was significantly correlated with OS in the multivariate analysis. In conclusion, Beclin 1 upregulation exacerbated the progression and aggressiveness of pancreatic neoplasms, and Bcl-2 downregulated expression was an independently poor prognostic factor for PDAC.

Keywords: B-cell lymphoma 2; Beclin 1; immunohistochemistry; pancreatic ductal adenocarcinoma; solid pseudopapillary neoplasm.