Objectives: The diagnosis of high-grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low-grade IPMN. The aim of this study was to identify potential markers for the discrimination of high-grade and invasive (HgInv) IPMN from low-and moderate-grade dysplasia IPMN. Methods: Laser capture microdissection was used to isolate distinct foci of low-grade, moderate-grade, high-grade, and invasive IPMN from paraffin-embedded archival tissue from 14 patients who

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... t resection for IPMN. Most samples included multiple grades in the same specimen. Affymetrix Human Exon microarrays were used to compare low-and moderate-grade dysplasia IPMN with HgInv IPMN. Results: Sixty-two genes were identified as showing significant changes in expression (P e 0.05 and a 2-fold cutoff ), including up-regulation of 41 in HgInv IPMN. Changes in gene expression are associated with biological processes related to malignant behavior including cell motion, cell proliferation, response to hypoxia, and epithelial-to-mesenchymal transition. In addition, altered signaling in several transforming growth factor AYrelated pathways was exhibited in the progression of IPMN to malignancy. Conclusions: This study identifies a set of genes associated with the progression of IPMN to malignancy. These genes are potential markers that could be used to identify IPMN requiring surgical resection.