Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections

• Published in: Histopathology Vol. 59; no. 5; pp. 832 - 840
• Main Authors: Lee, Stephen, de Boer, Willem Bastiaan, Fermoyle, Soraya, Platten, Michael, Kumarasinghe, Marian Priyanthi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-11-2011; Blackwell
• Subjects: Adenocarcinoma - genetics; Biological and medical sciences; Biopsy; Gastrectomy; gastric cancer; gastric dysplasia; Gastroenterology. Liver. Pancreas. Abdomen; Genes, erbB-2 - genetics; HER2; heterogeneity; Humans; Immunohistochemistry; In Situ Hybridization; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Precancerous Conditions - genetics; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - genetics; Reproducibility of Results; Stomach Neoplasms - genetics; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Immunohistochemistry; Molecular hybridization; gastric dysplasia; erbB2 Gene; Stomach cancer; Stomach carcinoma; Heterogeneity; Protooncogene; Gastric disease; Stomach; Dysplasia; gastric cancer; Digestive system; HER2 immunohistochemistry; Surgical resection; Malignant tumor; in-situ hybridization; Medical screening; Human Epidermal growth factor Receptor 2; Anatomic pathology; Biopsy; C-Onc gene; Digestive diseases; In situ hybridization; Cancer
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2011.04017.x

Lee S, de Boer W B, Fermoyle S, Platten M & Kumarasinghe M P 
(2011) Histopathology59, 832–840
Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections
Aims:  To assess human epidermal growth factor receptor 2 (HER2) status and heterogeneity using immunohistochemistry (IHC) and silver in‐situ hybridization (SISH) in gastric carcinoma and dysplasia, and to correlate HER2 status between biopsy and resection specimens of gastric carcinoma.
Methods and results:  Immunohistochemistry for HER2 was performed in 178 cases of gastric carcinoma, and SISH in cases showing at least 1+ reaction. HER2 positivity [European Medicines Agency (EMA) guidelines] was identified in 20.2% of carcinomas and 12.9% of high‐grade dysplasia, and HER2 heterogeneity noted in 50% and 33% of these cases, respectively. IHC negative/positive reactivity and SISH results were concordant in 96.2%. SISH amplification was seen in 35.3% of IHC 2+ and in a case with previously unrecognized staining pattern. Concordance of IHC HER2 status on biopsies and gastrectomies was seen in 74.1%. False negative IHC results on either the biopsy or gastrectomy were seen in 19.4% of HER2 amplified cases.
Conclusions:  Human epidermal growth factor receptor 2 status in gastric carcinoma is comparable to previous studies with good concordance between IHC and SISH; all IHC 2+ and unusual patterns should be assessed with ISH studies; heterogeneity of tumour HER2 overexpression/amplification is common with possible implications for HER2 testing; and HER2 overexpression appears sufficiently specific to be considered a potential diagnostic biomarker of dysplasia.