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, bar and mcl-1 and caspases 3, 6 and 8 and apoptosis in pancreatic carcinoma. Methods and results: Eighty-seven pancreatic carcinomas were studied immuno histochemically with antibodies to bcl-2, mcl-1, bar and caspases 3, 6 and 8. Apoptosis was detected by the TUNEL method. bcl-2 and mcl-1 positivity w as observed in 13% and 86% of the cases, while bar was observed in all of t hem, The bar immunoreactivity was weak in 30% of the tumours. Caspase 3, 6 and 8 immunoreactivity was observed in 80%, 80% and 74% of the cases, respe ctively. The staining was mainly cytoplasmic and diffuse, but sometimes als o fragmented granular (mainly caspase 6) or membrane-associated (mainly cas pase 8) staining was seen. The mean apoptotic index in pancreatic carcinoma s 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 apoptoti c index was higher in tumours with strong bar immunoreactivity (0.70%) than in the other cases (0.34%) (P = 0.002). There was no significant associati on between the apoptotic index and the expression of mcl-1 or caspases 3, 6 and 8. Conclusions: Both bcl-2 and bar influence the extent of apoptosis in pancre atic carcinoma. The strong expression of caspases 3, 6 and 8 in pancreatic carcinoma is evidence of the activation of the apoptotic machinery in malig nant cells in pancreatic carcinoma and shows that the genes of these protei ns are often upregulated in them.