Immunohistochemical and Molecular Characterization of Incipient Intraductal Papillary Mucinous Neoplasms
C Shi, S-M Hong, P Lim, JR Eshleman, M Goggins, RH Hruban. The Johns Hopkins Medical Institutions, Baltimore, MD
Background: Intraductal papillary mucinous neoplasms (IPMN) are grossly visible mucin-producing epithelial neoplasms often with prominent papillary architecture that arise predominantly in the main pancreatic duct or its branches. Incipient IPMNs are histologically similar to IPMNs, but they are <1cm and fall short of size criteria for an IPMN. Some investigators have suggested that incipient IPMN may represent an early stage of the development of IPMN. The goal of this study is to characterize incipient IPMNs using immunohistochemical labeling and KRAS2 gene mutation analysis.
Design: Formalin-fixed, paraffin-embedded sections were immunolabeled with antibodies to MUC-1, MUC-2, CDX-2, DPC4, E-cadherin, P53, P16 and cyclin D1. KRAS2 gene status was analyzed by PCR DNA sequencing using DNA isolated from microdissected samples.
Results: Twenty two incipient IPMNs were identified: 16 with low-grade dysplasia and 6 with moderate dysplasia. The size of the incipient IPMNs ranged from 0.2 cm to 0.8 cm. MUC-1 was expressed in 5 of 22 lesions (22.7%), whereas MUC-2 expression was only detected in one lesion (4.5%). No lesions were immunoreactive for CDX2. DPC4 and E-cadherin expression were both intact in all of the lesions. P53 immunoreactivity was seen in 2 of 22 lesions (9.1%). Overexpression of cyclin D1 was present in 10 of 22 lesions (45.5%). Four of 20 (20%) lesions demonstrated loss of p16 expression. KRAS2 gene sequencing revealed that 5 out of 6 lesions (83.3%) harbored a codon 12 mutation.
Conclusions: Incipient IPMNs demonstrated a high frequency of KRAS2 gene mutations and low frequency of MUC-2 expression as seen in PanIN. On the other hand, similar to IPMN, they also showed a low rate of P16 loss. This data suggests that incipient IPMN may represent a transitional lesion between PanIN and IPMN lesions.
Category: Liver & Pancreas
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 242, Wednesday Morning