title: 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: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, 35121 Padua, Italy.
authors: Rocco
authors: R
authors: Cappellesso
authors: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, 35121 Padua, Italy.
authors: Matteo
authors: M
authors: Fassan
authors: Pathology Service, Regional General Hospital, 39100 Bolzano, Italy.
authors: Esther
authors: E
authors: Hanspeter
authors: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, 39106 Magdeburg, Germany.
authors: Jan
authors: J
authors: Bornschein
authors: Department of Pathology, San Bortolo Hospital, 36100 Vicenza, Italy.
authors: Emanuele S G
authors: ES
authors: d'Amore
authors: Surgical Pathology Unit, Molecular Pathology Laboratory, Trentino Biobank, S. Chiara Hospital, 38122 Trento, Italy.
authors: Lucia V
authors: LV
authors: Cuorvo
authors: Pathology Service, Regional General Hospital, 39100 Bolzano, Italy.
authors: Guido
authors: G
authors: Mazzoleni
authors: Surgical Pathology Unit, Molecular Pathology Laboratory, Trentino Biobank, S. Chiara Hospital, 38122 Trento, Italy.
authors: Mattia
authors: M
authors: Barbareschi
authors: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, 35121 Padua, Italy.
authors: Marco
authors: M
authors: Pizzi
authors: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, 35121 Padua, Italy.
authors: Vincenza
authors: V
authors: Guzzardo
authors: Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, 39106 Magdeburg, Germany.
authors: Peter
authors: P
authors: Malfertheiner
authors: Department of Pathology, First Surgical University Hospital, Clinical Center of Serbia, University of Belgrade, 11000 Belgrade, Serbia.
authors: Marjan
authors: M
authors: Micev
authors: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, 35121 Padua, Italy; Pathology Department, ULSS15 Alta Padovana, 35013 Padua, Italy.
authors: Maria
authors: M
authors: Guido
authors: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, 35121 Padua, Italy.
authors: Luciano
authors: L
authors: Giacomelli
authors: State Scientific Medical Research Institute for Northern Problems of Siberian Division of Russian Academy of Medical Sciences, 660000 Krasnoyarsk, Russia.
authors: Vladislav V
authors: VV
authors: Tsukanov
authors: Istituto Oncologico Veneto, 35128 Padua, Italy.
authors: Vittorina
authors: V
authors: Zagonel
authors: Department of Surgery, University of 35128 Padua, Padua, Italy.
authors: Donato
authors: D
authors: Nitti
authors: Department of Medicine, Surgical Pathology and Cytopathology Unit, University of Padua, 35121 Padua, Italy. Electronic address: massimo.rugge@unipd.it.
authors: Massimo
authors: M
authors: Rugge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D046888:Tissue Array Analysis / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: CISH; Gastric cancer; Gastroesophageal cancer; HER2; Immunohistochemistry