Spontaneous apoptosis and proliferation in human pancreatic cancer.

Several studies have documented the role of programmed cell death in the development and/or progression of cancer. The aims of this study were to analyze (a) the spontaneous apoptosis in human pancreatic duct carcinoma by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL); (b) its correlation with the proliferation rate of the tumor (determined by immunohistochemistry by using monoclonal antibody MIB-1); and (c) the association of apoptotic and mitotic index with the histologic features of the tumor and the outcome of patients. In pancreatic cancer, the apoptotic index (AI) was 4.9 +/- 4.8, and the mitotic index (MI) was 1.3 +/- 1.0 (mean +/- SD). AI was higher in small (<4 cm) than in large (>4 cm) size primary tumors (p = 0.02) and in undifferentiated as compared with differentiated cancers (p = 0.05). Significantly higher values of MI were detected in advanced as compared with early-stage carcinomas (p = 0.03) and when perineural invasion was present (p = 0.03). No correlation was found between AI and MI. Patients with AI > 2.3 survived significantly less than those with lower AI values (p = 0.03). Mitotic index >0.5 was associated with a worse survival (p = 0.006). These results suggest that in pancreatic cancer, spontaneous apoptosis is present and is more evident in small and undifferentiated tumors. Proliferation is increased in the advanced stage of cancer and seems to be independent of apoptosis. Higher levels of apoptosis and proliferation are negative prognostic indexes.