The pattern of CPP32/caspase-3 expression reflects the biological behaviorof 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 papill ary-mucinous tumor of the pancreas (IPMT) is a unique tumor that grows intr aductally with rare stromal invasion. However, it is not possible to distin guish noninvasive from invasive IPMT preoperatively. To examine whether cas pase-3 expression reflects the biological behavior of pancreatic tumors, we investigated this enzyme expression by reverse transcription-polymerase ch ain reaction (RT-PCR) and immunohistochemistry in 22 pancreatic duct cell c arcinomas (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 s ignificant correlation between the cytoplasmic staining and malignant grade of the tumors. In contrast, the nuclear expression of this enzyme was sign ificantly higher in noninvasive than in invasive tumors (p = 0.0015). Cytop lasmic expression of caspase-3 may be related to the invasiveness of pancre atic tumors. In contrast, nuclear expression of this enzyme may reflect the benign biological behavior of IPMT.