Survivin Expression in Pancreatic Intraepithelial Neoplasia (PanIN): Steady Increase Along the Developmental Stages of Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive gastrointestinal cancers and is thought to arise from noninvasive precursors-pancreatic intraepithelial neoplasia (PanIN). Aberrantly prolonged cell survival due to apoptosis suppression is likely to contribute to carcinogenesis and carcinoma progression where the inhibitor of apoptosis proteins (IAPs) may play an important role. IAPs specifically inhibit caspases 3, 7, and 9 and prevent apoptosis. Survivin is a unique member of the IAPs family that is expressed in most human cancers including PDA but is not expressed in most normal adult tissues. To measure survivin transcript levels in normal pancreatic ducts, PanINs, and PDA, we used laser capture microdissection and real-time polymerase chain reaction. Survivin protein expression in normal pancreatic ducts, PanINs, PDA, and its metastases to lymph nodes were evaluated by immunohistochemistry. In microdissected tissues, we found a steady and close to exponential increase in survivin transcript levels from low-grade lesions (PanINs-1) to high-grade lesions (PanINs-2 and 3) and further to PDA. This observation was strictly mirrored by survivin protein expression. In addition, survivin was localized to the nucleus in high-grade lesions (starting at PanIN-2 stage), PDA, and nodal metastases, suggesting that nuclear translocation of survivin may be an early event in transformation to malignancy.