HER2 status in gastroesophageal cancer: a tissue microarray study of 1040 cases.

Abstract

Among patients with gastric cancer (GC) and gastroesophageal cancer (G-EC), HER2 amplification identifies those who may benefit from trastuzumab. HER2 status assessment, however, is influenced by preanalytic, analytic, and postanalytic variables. In a series of 5426 microarray cancer tissue cores obtained from 1040 GC/G-ECs (824 GC, 216 G-EC) and 720 synchronous nodal metastases, we evaluated both the performances of 2 different immunohistochemistry (IHC) protocols and the HER2 status intratumor variability. The prevalence of HER2 amplification and protein overexpression were assessed by chromogenic in situ hybridization and by 2 IHC protocols (CB11 and 4B5). HER2 was amplified in 114 (11%) of 1040 cases; in 6 (5.3%) of 114 cases, gene amplification only involved nodal metastasis. HER2 amplification prevailed in intestinal-type (P = .001) and low-grade (P < .001) tumors, showing no correlation with patients' age/sex, tumor location, stage, and Ming histotype. Overall, 12.5% and 13.7% of cases IHC scored 2+/3+ using the CB11-IHC and the 4B5-IHC protocol, respectively. HER2 amplification was not associated with protein overexpression (score 0/1+) in 11.4% and 6.2% of cases using the CB11-IHC and the 4B5-IHC protocol, respectively. The 4B5-IHC protocol proved more sensitive than CB11-IHC (93.9% versus 88.6%) and just as specific (96.1% versus 96.9%). Tested by chromogenic in situ hybridization, intratumor HER2 status was "substantially" consistent in different tissue cores obtained from the same case (κ = 0.78). Similar results were obtained for HER2 protein expression (CB11-IHC, κ = 0.78, and 4B5-IHC, κ = 0.83). Immunohistochemistry testing, however, fails in identifying about 10% of HER2-amplified cancers, potentially excluding these patients from anti-HER2 therapy.

• Authors: Rocco Cappellesso, Matteo Fassan, Esther Hanspeter, Jan Bornschein, Emanuele S G d'Amore, Lucia V Cuorvo, Guido Mazzoleni, Mattia Barbareschi, Marco Pizzi, Vincenza Guzzardo, Peter Malfertheiner, Marjan Micev, Maria Guido, Luciano Giacomelli, Vladislav V Tsukanov, Vittorina Zagonel, Donato Nitti, Massimo Rugge
• Journal: Human pathology (Hum Pathol) Vol. 46 Issue 5 Pg. 665-72 (May 2015) ISSN: 1532-8392 [Electronic] United States
• PMID: 25800719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (analysis, metabolism)
• Esophageal Neoplasms (metabolism)
• Female
• Gene Amplification
• Humans
• Immunohistochemistry (methods)
• In Situ Hybridization (methods)
• Male
• Middle Aged
• Receptor, ErbB-2 (genetics, metabolism)
• Stomach Neoplasms (genetics, pathology)
• Tissue Array Analysis (methods)