p27 Kip1 expression is reduced in pancreatic carcinoma but has limited prognostic value

Abstract

p27(Kip1) is a cyclin-dependent kinase inhibitor whose loss in malignant tumors is associated with disease progression and an unfavorable clinical outcome. There is limited information about its expression in pancreatic carcinomas. In a previous Japanese study, p27(Kip1) loss was a powerful negative prognostic factor. In the present study, we assessed the expression of p27(Kip1) in resected pancreatic ductal adenocarcinomas from 46 European patients and in associated lymph node metastases from 13 patients, using a standard avidin-biotin peroxidase complex immunohistochemical method. We also analyzed the relationships among p27(Kip1) expression, pathologic features, and clinical outcome. The extent of p27(Kip1) expression (ie, the percentage of cells expressing p27(Kip1)) was lower in carcinomas than in nonneoplastic ductal epithelia. Carcinomas with <5% p27(Kip1) expression were more likely to be poorly or moderately differentiated than well differentiated (P =.022). p27(Kip1) expression did not correlate with patient gender, tumor maximum dimension, T classification, lymph node metastasis, or International Union Against Cancer stage. No significant difference was seen between the extent of p27(Kip1) expression in lymph node metastases and their corresponding primary tumors. Univariate survival analysis showed that an increased risk of death was associated with 2 established prognostic factors: tumor size >5 cm (P =.011) and incomplete surgical excision (P =.016). Trends toward worse survival for patients whose primary tumors had <4% p27(Kip1) expression (P =.060) and for patients whose lymph node metastases had <5% p27(Kip1) expression (P =.054) were seen, but multivariate analysis suggested that p27(Kip1) expression was not independently prognostic. The findings raise the possibility that abnormalities of p27(Kip1) play a role in the pathogenesis of pancreatic ductal adenocarcinoma. However, the extent of p27(Kip1) expression in lymph node metastases and primary tumors is similar. Also, reduced p27(Kip1) expression has limited prognostic value, at least in European patients.