MiR-21 up-regulation in ampullary adenocarcinoma and its pre-invasive lesions

Abstract Poor information is available on the molecular landscape characterizing the carcinogenetic process leading to ampullary carcinoma. MiR-21 is one of the most frequently up-regulated miRNAs in pancreatic adenocarcinoma, a tumor sharing similar molecular features with ampullary adenocarcinomas (AVCs), above all with the pancreatic-biliary type. We profiled, by in situ hybridization (ISH), miR-21 expression in a series of 26 AVCs, 50 ampullary dysplastic lesions (35 low-grade [LG-IEN] and 15 high-grade [HG-IEN]) and 10 normal duodenal mucosa samples. The same series was investigated by immunohistochemistry for β-catenin, p53 and HER2 expression. HER2 gene amplification was evaluated by chromogenic in situ hybridization. To validate miR-21 ISH results we performed miR-21 qRT-PCR analysis in a series of 10 AVCs and their matched normal samples. All the normal control samples showed a negative or faint miR-21 expression, whereas a significant miR-21 up-regulation was observed during the carcinogenetic cascade (p