Different patterns of p16INK4A and p53 protein expressions in intraductal papillary-mucinous neoplasms and pancreatic intraepithelial neoplasia

Objectives: To examine aberrations and differences of cell cycle regulatory proteins between intraductal papillary-mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasias (PanINs). Methods: In total, 47 IPMN lesions and 42 PanIN lesions were obtained from 26 patients with IPMN and 16 patients who underwent pancreatic surgery for invasive pancreatic ductal cancer or other diseases. They were subjected to conventional hematoxylin-eosin staining and immunostaining for p16INK4A and p53. The percentages of immunohistochemical positivity or negativity were compared between IPMN and PanIN, in accordance with the same histological grade of atypia. The Ki-67 labeling index was also counted in each lesion. Results: Either the loss of p16INK4A expression or the overexpression of p53 was much more frequently observed among PanIN-3 than among carcinoma in situ in IPMN (P 0.046 and 0.008, respectively). The Ki-67 labeling index was correlated with the histological grades of both PanINs and IPNMs (P = 0.0001 and P 0.0001, respectively). Conclusions: There are different inummohistochemical expression patterns of p16INK4A and p53 between IPMNs and PanINs. These may substantiate their different genetic progressions to invasive carcinoma.