MicroRNA Analysis May Help To Identify High-Grade Dysplasia in Intraductal Papillary Mucinous Neoplasms
NC Panarelli, Y-T Chen, XK Zhou, RK Yantiss. Weill Cornell Medical College, New York, NY
Background: Intraductal papillary mucinous neoplasms (IPMNs) are dysplastic pancreatic cystic lesions that show a spectrum of epithelial cell dysplasia ranging from minimal atypia to carcinoma in situ and, importantly, may precede some invasive pancreatic ductal carcinomas (PDCAs). IPMNs with mild or moderate dysplasia are often clinically followed, whereas those with severe dysplasia are generally resected due to perceived cancer risk. Unfortunately, the preoperative classification of IPMNs may be hampered by limited material and/or superimposed inflammatory changes present in biopsy samples. Therefore, molecular markers that aid the distinction between low- and high-risk IPMNs are needed.
Design: We evaluated microRNA (miRNA) expression in IPMNs and PDCAs using microarrays and subsequent quantitative RT-PCR for validation. RNA was extracted from paraffin-embedded tumor sections (8 IPMNs and 8 PDCAs) and subjected to the Luminex microarray assay to identify differentially expressed miRNAs. The expression of selected miRNAs was then analyzed in low-grade (mild-to-moderate dysplasia, n=14) and high-grade (severe dysplasia, n=9) IPMNs. PDCAs (n=4) were analyzed as a control group. Median miRNA expression levels were recorded for each group and the results were statistically analyzed.
Results: Analysis of microarray data revealed higher expression of miR-21 and -155 among PDCAs compared to IPMNs, and these results were confirmed by qRT-PCR (p=0.01 and 0.02, respectively). The Luminex assay also revealed higher expression of miR-375, -494, -542-3p, and -363 in IPMNs relative to PDCAs, but qRT-PCR confirmed higher expression of only miR-375 (p=0.07). Pair-wise comparisons between the groups showed higher miR-375 expression in low-grade IPMNs compared to both high-grade IPMNs (p=0.06) and PDCAs (p=0.05). Although expression of miR-21 and miR-155 was increased in PDCAs compared to IPMNs, low- and high-grade IPMNs showed similar expression of these markers.
Conclusions: Pancreatic ductal carcinomas show significantly higher expression of miR-21 and -155 compared to IPMNs, indicating that these biomarkers may aid detection of early carcinoma in cystic pancreatic lesions. Expression of miR-375, a microRNA normally found in non-neoplastic pancreas, was higher in low-grade IPMNs than high-grade dysplasia and invasive carcinoma, suggesting that miRNA analysis may also aid the preoperative classification of IPMNs.
Category: Liver & Pancreas
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 202, Tuesday Afternoon