The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis

Matteo Fassan, Marco Pizzi, Stefano Realdon, Mariangela Balistreri, Vincenza Guzzardo, Vittorina Zagonel, Carlo Castoro, Luca Mastracci, Fabio Farinati, Donato Nitti, Giovanni Zaninotto, Massimo Rugge

Research output: Contribution to journalArticlepeer-review

Abstract

A subset of gastric (intestinal-type) and esophageal (Barrett) adenocarcinoma features HER2 protein overexpression. Consistent evidence demonstrates that microRNAs have a major role in HER2 (dys)regulation. MiR-125a-5p and miR125b expressions were tested in the spectrum of lesions in the gastroesophageal carcinogenic cascade, also correlating miR-125a-5p/125b levels with HER2 status. MiR-125a-5p and miR-125b expression (quantitative reverse transcriptase polymerase chain reaction [qRT-PCR]) and HER2 status (immunohistochemistry [IHC] and chromogenic in situ hybridization [CISH]) were assessed in a series of 90 biopsy samples spanning the whole histologic spectrum of gastric and esophageal carcinogenesis. To support the obtained results, the qRT-PCR levels of microRNAs and their expression (in situ hybridization) were tested in an adjunctive series of gastric and esophageal adenocarcinoma, including (IHC/CISH validated) HER2-negative and HER2-positive cases. Both miR-125a-5p and miR-125b levels were significantly down-regulated throughout the gastric and esophageal carcinogenic cascade. HER2 status (IHC and CISH) correlated inversely with miR-125 expression (qRT-PCR and in situ hybridization). Dysregulation of miR-125a-5p/125b and HER2 is an early event in the gastric (intestinal-type) and esophageal (Barrett) oncogenesis. In both oncogenetic cascades, miR-125 expression correlates inversely with HER2 status. MiR-125a-5p/125b can be considered among the therapeutic targets in HER2-positive esophageal and gastric adenocarcinoma.

Original languageEnglish
Pages (from-to)1804-1810
Number of pages7
JournalHuman Pathology
Volume44
Issue number9
DOIs
Publication statusPublished - Sep 2013

Keywords

  • Gastroesophageal cancer
  • HER2
  • miRNAs

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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