Apoptosis in gallbladder carcinomas and dysplasias, its relation to the expression of caspases 3, 6 and 8 and apoptosis regulating proteins bcl-2, mcl-1 and bax

In this study we investigated apoptosis and the expression of caspases 3, 6 and 8 and bcl-2, mcl-1 and bax in 39 gallbladder carcinomas and 7 epithelial dysplasias. The average apoptotic index was 0.68 +/- 0.91%. The extent of apoptosis was higher in grade II-III than grade I tumours or epithelial dysplasias (p = 0.003). Also, tumours invading beyond serosa or into other organs (T3-T4) had a higher apoptotic index than other tumours (p = 0.05). Caspase 3 expression was found in 37 (95%) and caspase 6 and 8 expression each in 30 (77%) carcinomas. Their expression associated with each other and tended to increase along with the progression of the lesions. Bcl-2 expression was found in only 4 (10%) tumours. In contrast, mcl-1 positivity was found in 34 (87%) and bax positivity in all cases. The results show that apoptosis is increased along with progression of the neoplastic lesions of the gallbladder epithelium. Caspases 3, 6 and 8 are strongly expressed in gallbladder carcinomas suggesting that they contribute to the increased apoptosis observed in them. Of the bcl-2 family proteins, bcl-2 was expressed infrequently suggesting that it does not play any significant role in apoptosis inhibition in gallbladder tumours.