Bcl-XL protein levels determine apoptotic index in pancreatic carcinoma

Objectives: The present study was designed to analyze the expression of the major antiapoptotic molecules Bcl-2, Bcl-X-L and the proapoptotic Bax in pancreatic ductal carcinoma and their correlation to the extent of apoptosis. Methods: Tissue samples were obtained from patients ( age, 27 - 78 years) having surgery for pancreatic cancer. Normal pancreatic tissue away from the main tumor mass was also analyzed. The levels of Bcl-2, Bcl-X-L, and Bax mRNA expression were analyzed by semiquantitative reverse transcriptase polymerase chain reaction ( RTPCR). The presence of corresponding proteins was determined by immunohistochemistry (IHC). The apoptotic index was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling ( TUNEL) assay. Results: A total of 25 cases were analyzed. The apoptotic index ( percentage) ranged from 0.0% to 1.8%, with a median of 0.26. Semiquantitative RT-PCR revealed variable mRNA expression, with the Bcl-2/Bax ratio ranging from 0.2 to 1.5 and the Bcl-X-L/Bax ratio ranging from 0.3 to 1.8. There was no correlation of mRNA levels with the apoptotic index. Immunohistochemical analysis showed positive Bcl-2, Bax, Bcl-X-L expression in 20%, 72%, and 92% of cancer samples; however, their levels were variable. Spearman rank correlation coefficient test revealed a significant inverse association for the Bcl-X-L IHC score and apoptotic index ( P< 0.05). In contrast, Bcl-2, Bax protein levels did not show any association with the apoptotic index. However, as compared with the normal pancreas, Bcl-2, Bcl-X-L, Bax were overexpressed in most of the pancreatic cancer samples (Mann-Whitney U test, P< 0.01). Conclusion: In pancreatic cancer, there is an upregulation of all the apoptotic regulatory molecules and the apoptotic index is chiefly determined by Bcl-X-L protein levels.