Spontaneous apoptosis and proliferation in human pancreatic cancer

Several studies have documented the role of programmed cell death in the de velopment and/or progression of cancer. The aims of this study were to anal yze (a) the spontaneous apoptosis in human pancreatic duct carcinoma by ter minal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL); (b) its correlation with the proliferation rate of the t umor (determined by immunohistochemistry by using monoclonal antibody MIB-1 ); and (c) the association of apoptotic and mitotic index with the histolog ic 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 wit h differentiated cancers (p = 0.05). Significantly higher values of MI were detected in advanced as compared with early-stage carcinomas (p = 0.03) an d 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 w ith a worse survival (p = 0.006). These results suggest that in pancreatic cancer, spontaneous apoptosis is present and is more evident in small and u ndifferentiated tumors. Proliferation is increased in the advanced stage of cancer and seems to be independent of apoptosis. Higher levels of apoptosi s and proliferation are negative prognostic indexes.