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.