title: The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis.
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.
authors.affiliation: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, 35100 Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.forename: Marco
authors.initials: M
authors.lastname: Pizzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Realdon
authors.forename: Mariangela
authors.initials: M
authors.lastname: Balistreri
authors.forename: Vincenza
authors.initials: V
authors.lastname: Guzzardo
authors.forename: Vittorina
authors.initials: V
authors.lastname: Zagonel
authors.forename: Carlo
authors.initials: C
authors.lastname: Castoro
authors.forename: Luca
authors.initials: L
authors.lastname: Mastracci
authors.forename: Fabio
authors.initials: F
authors.lastname: Farinati
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zaninotto
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D054337:Cell Dedifferentiation / Q000235:genetics; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; C531888:MIRN125 microRNA, human; C508053:ERBB2 protein, human
keywords: BAc; Barrett adenocarcinoma; CISH; GC; Gastroesophageal cancer; HER2; HG; IEN; IHC; KW; Kruskal-Wallis test; LG; SH; chromogenic in situ hybridization; gastric cancer; high grade; human epithelial growth factor receptor 2; immunohistochemistry; in situ hybridization; intraepithelial neoplasia/dysplasia; low grade; miRNAs