The pattern of CPP32/caspase-3 expression reflects the biological behavior of the human pancreatic duct cell tumors

Caspase-3/CPP32, a member of the Ced-3-family of cysteine proteases, is an important mediator of programmed cell death (apoptosis). Intraductal papillary-mucinous tumor of the pancreas (IPMT) is a unique tumor that grows intraductally with rare stromal invasion. However, it is not possible to distinguish noninvasive from invasive IPMT preoperatively. To examine whether caspase-3 expression reflects the biological behavior of pancreatic tumors, we investigated this enzyme expression by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry in 22 pancreatic duct cell carcinomas (PDC) and 13 TPMT cases. Caspase-3 mRNA was overexpressed in PDC and IPMT with carcinoma when compared with normal pancreatic tissue or IPMT with adeno-ma. The immunoreactivity of this enzyme was predominantly found in the cytoplasm of invasive tumors (PDC and invasive IPMT). There was a significant correlation between the cytoplasmic staining and malignant grade of the tumors. In contrast, the nuclear expression of this enzyme was significantly higher in noninvasive than in invasive tumors (p = 0.0015). Cytoplasmic expression of caspase-3 may be related to the invasiveness of pancreatic tumors. In contrast, nuclear expression of this enzyme may reflect the benign biological behavior of IPMT.