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The HER2-miR125a5p/miR125b loop in gastric and esophageal carcinogenesis.
- Source :
-
Human pathology [Hum Pathol] 2013 Sep; Vol. 44 (9), pp. 1804-10. Date of Electronic Publication: 2013 Apr 22. - Publication Year :
- 2013
-
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.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Adenocarcinoma metabolism
Adenocarcinoma pathology
Aged
Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Cell Dedifferentiation genetics
Cell Line, Tumor
Esophageal Neoplasms metabolism
Esophageal Neoplasms pathology
Gene Expression Regulation, Neoplastic
Humans
Male
MicroRNAs metabolism
Receptor, ErbB-2 metabolism
Retrospective Studies
Stomach Neoplasms metabolism
Stomach Neoplasms pathology
Adenocarcinoma genetics
Esophageal Neoplasms genetics
MicroRNAs genetics
Receptor, ErbB-2 genetics
Stomach Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-8392
- Volume :
- 44
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Human pathology
- Publication Type :
- Academic Journal
- Accession number :
- 23618359
- Full Text :
- https://doi.org/10.1016/j.humpath.2013.01.023