Apoptotic index and apoptosis influencing proteins bcl-2, mcl-1, bax and caspases 3, 6 and 8 in pancreatic carcinoma

Aims: To study the expression of bcl-2, bax and mcl-1 and caspases 3, 6 and 8 and apoptosis in pancreatic carcinoma. Methods and results: Eighty-seven pancreatic carcinomas were studied immunohistochemically with antibodies to bcl-2, mcl-1, bax and caspases 3, 6 and 8. Apoptosis was detected by the TUNEL method. bcl-2 and mcl-1 positivity was observed in 13% and 86% of the cases, while bax was observed in all of them, The bax immunoreactivity was weak in 30% of the tumours. Caspase 3, 6 and 8 immunoreactivity was observed in 80%, 80% and 74% of the cases, respectively. The staining was mainly cytoplasmic and diffuse, but sometimes also fragmented granular (mainly caspase 6) or membrane-associated (mainly caspase 8) staining was seen. The mean apoptotic index in pancreatic carcinomas was 0.69%. The apoptotic index in bcl-2 positive cases was lower (0.35%) than in cases showing no immunoreactivity (0.64%) (P = 0.013). The apoptotic index was higher in tumours with strong bax immunoreactivity (0.70%) than in the other cases (0.34%) (P = 0.002). There was no significant association between the apoptotic index and the expression of mcl-1 or caspases 3, 6 and 8. Conclusions: Both bcl-2 and bax influence the extent of apoptosis in pancreatic carcinoma. The strong expression of caspases 3, 6 and 8 in pancreatic carcinoma is evidence of the activation of the apoptotic machinery in malignant cells in pancreatic carcinoma and shows that the genes of these proteins are often upregulated in them.