Gene amplification of ERBB2 and EGFR in adenocarcinoma in situ and intramucosal adenocarcinoma of Barrett's esophagus.
We examined 11 cases of carcinoma arising from Barrett's esophagus consisting of two adenocarcinomas in situ (ACIS), two intramucosal adenocarcinomas, and seven overt invasive adenocarcinomas. Overexpression of p53 (implying a mutation of the p53 gene), ERBB2, and EGFR was measured by immunohistochemistry, and gene amplification of ERBB2 and EGFR was measured by fluorescence in situ hybridization (FISH). In all cases of ACIS and the intramucosal adenocarcinomas, almost all cancer cells overexpressed p53, however the populations overexpressing ERBB2 and EGFR varied in different cases: in one ACIS, ERBB2 was coexpressed in all the cancer cells, in the other ACIS and one intramucosal adenocarcinoma, ERBB2 was overexpressed in about 50% and only 10% of the p53-positive cells respectively. EGFR was co-expressed in 20% in the other intramucosal adenocarcinoma. Protein overexpression of ERBB2 or EGFR corresponded to the amplification of their respective genes on a cell by cell basis. These gene amplifications, however, were not found in the seven invasive adenocarcinomas. Thus we speculate that the gene amplification occurred late in the dysplasia-carcinoma sequence probably after the mutation of p53. Furthermore, new clonal expansion accompanied by tumor invasion might have extinguished the originally amplified genes in these tumors.
Department of Molecular and Cellular Pathology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan. aooi@med.kanazawa-u.ac.jp
Akishi
A
Ooi
Yoh
Y
Zen
Itasu
I
Ninomiya
Ryousuke
R
Tajiri
Shioto
S
Suzuki
Hideaki
H
Kobayashi
Issei
I
Imoto
Yoh
Y
Dobashi
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001471:Barrett Esophagus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002278:Carcinoma in Situ / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; C508053:ERBB2 protein, human