Immunohistochemical localization of caspase-3 correlates with clinical outcome in B-cell diffuse large-cell lymphoma

Although B-cell diffuse large-cell lymphoma (DLCL) can respond to chemother apy and radiotherapy, a large number of patients are still resistant to tre atment. Caspase-3 is an enzyme crucial to the apoptotic process and may be important in the clinical outcome of these patients, The pattern of caspase -3 expression was studied in 54 eases of DLCL using immunohistochemistry an d quantitative reverse-transcription PCR, Tumor cells displayed both a diff use cytosolic and a punctate cytosolic staining for caspase-3, Kaplan-Meier survival curves indicated that tumor cells with a diffuse cytosolic expres sion of caspase-3 correlated with a poor prognosis (P > 0.0004). In additio n, a punctate cellular Localization was associated with complete response t o treatment (P = 0.011). Cases with a small percentage of lymphoma cells ex pressing caspase-3 also tended to show poor survival (P > 0.09). Levels of caspase-3 mRNA were not significant (P > 0.17), although a weak trend,vas o bserved similar to the immunohistochemical analysis, The pattern of express ion of caspase-3 was also assessed with respect to terminal deoxynucleotidy l transferase-mediated nick end labeling (TUNEL) positivity in both reactiv e lymph nodes and B-cell DLCL cases, Our results suggest that TUNEL-positiv e cells are not caspase-3-positive and that there is no correlation between DLCL cases with a high degree of DNA fragmentation and caspase-3 immunosta ining, Furthermore, a survival curve indicated that a high TUNEL positivity was associated with a poor survival probability (p < 0.02) and a poor resp onse to treatment (P = 0.04). These results confirm the dynamic nature of c aspase-3 expression In DLCL and suggests that the pattern of expression of the enzyme has prognostic significance.