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

Saraggi, D. et al. (2018) MiR-21 up-regulation in ampullary adenocarcinoma and its pre-invasive lesions. Pathology: Research and Practice, 214(6), pp. 835-839. (doi: 10.1016/j.prp.2018.04.018) (PMID:29731265)

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 < 0.001), with 21/26 (80.8%) of cancer samples showing a miR-21 overexpression. In comparison to control samples, a significant overexpression was found in samples of LG-IEN (p = .0003), HG-IEN (p = .0001), and AVCs (p < 0.0001). No significant difference in miR-21 overexpression was observed between LG-IEN, HG-IEN and AVCs. By qRT-PCR analysis, AVCs showed a 1.7-fold increase over the controls (p = .003). P53 was frequently dysregulated in both dysplastic and carcinoma samples (44 out of 76; 57.9%). A 20% (10/50) of dysplastic lesions and 11% (3/26) of carcinomas were characterized by a nuclear localization of β-catenin. Only 2 AVCs (7.7%; both intestinal-type) showed a HER2 overexpression (both 2+), which corresponded to a HER2 gene amplification at CISH analysis. This is the first study demonstrating a miRNA dysregulation in the whole spectrum of ampullary carcinogenesis. MiR-21 overexpression is an early molecular event during ampullary carcinogenesis and its levels increase with the neoplastic progression.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Braconi, Professor Chiara
• Authors: Saraggi, D., Galuppini, F., Fanelli, G. N., Remo, A., Urso, E. D.L., Bao, R. Q., Bacchin, D., Guzzardo, V., Luchini, C., Braconi, C., Farinati, F., Rugge, M., and Fassan, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Pathology: Research and Practice
• Publisher: Elsevier
• ISSN: 0344-0338
• ISSN (Online): 1618-0631
• Published Online: 01 May 2018
• Copyright Holders: Copyright © 2018 Elsevier GmbH.
• First Published: First published in Pathology: Research and Practice 214(6):835-839
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher