Increased K-ras mutation and expression of S100A4 and MUC2 protein in the malignant intraductal papillary mucinous tumor of the pancreas

Abstract

Purpose: The purpose of this study was to document the biological changes during the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN) and to identify biological markers capable of differentiating benign and malignant IPMN.

Methods: Forty-one patients with IPMN who underwent resection between 1994 and 2003 were enrolled in this study. The paraffin-embedded tumors from 27 with benign IPMNs and from 14 with IPMCs were subjected to immunohistochemical staining and DNA extraction. Direct DNA sequencing analysis for K-ras mutation and immunohistochemical staining using 17 biological markers was performed.

Results: K-ras mutations at codon 12 and 13 were detected in 13 of 37 (38.2%) of the IPMNs: in 5 of 24 (20.8%) of benign IPMNs, and in 8 of 13 (61.5%) of malignant IPMNs (p = 0.028). The expression of S100A4 and MUC2 were increased in malignant IPMNs. S100A4 was expressed in 2 (7.4%) of 27 benign IPMNs, and 6 (42.9%) of 14 malignant IPMNs (p = 0.007). MUC2 was expressed in 2 (7.4%) benign IPMNs, and in 9 (64.3%) malignant IPMNs (p < 0.001).

Conclusion: K-ras mutation and the expression of S100A4 and MUC2 (especially in intestinal subtype) were found to be related to malignancy in IPMN, and may be useful for the diagnosis and for assessing the biological behavior of IPMN.