Apoptosis and expression of caspases 3, 6 and 8 in malignant non-Hodgkin's lymphomas

In this study we investigated the immunohistochemical expression of caspases 3, 6 and 8 in 85 malignant non-Hodgkin's lymphomas and in 4 hyperplastic lymph nodes. The extent of apoptosis and the immunohistochemical expression of bcl-2 and bax was also studied. Caspase 3 immunoreactivity was seen in 84/85 (99%), caspase 6 in 46/85 (54%), and caspase 8 in 66/85 (78%) lymphomas. The immunoreactivity for caspase 3 was diffuse cytoplasmic while antibodies to caspase 6 and 8 showed granular and fragmented, sometimes also nuclear immunopositivity. High-grade non-Hodgkin's lymphomas expressed strong caspase 6 and 8 immunoreactivity significantly more often than low-grade lymphomas (p = 0.016 and p = 0.0002, respectively). Strong caspase 3 immunoreactivity was also seen more often in high-grade lymphomas, but the association did not reach statistical significance (p = 0.14). There was a strong association between the expression of caspase 3 and 6 (p = 0.032), caspase 3 and 8 (p = 0.042), and especially between caspase 6 and 8 (p = <0.00001). There was a significant difference in the apoptotic index between low-grade (0.59+/-0.44%) and high-grade lymphomas (1.96+/-1.92%) (p<0.001). Strong bcl-2 expression was seen in 35/80 (44%) and strong bax expression in 20/80 (25%) lymphomas. No significant association was found between the expression of bcl-2 or bax and the expression of the caspases. According to the results the expression of caspases 6 and 8 is upregulated in high-grade compared with low-grade lymphomas and probably contributes to the execution of apoptosis in them. A similar tendency could also be seen with caspase 3. The expression of the three caspases is significantly associated, suggesting that it is mutually regulated. Finally, the results suggest that the expression of bcl-2 or bax does not influence the expression of caspases 3, 6 and 8 in malignant lymphomas to a significant degree.