PMID- 21323962 OWN - NLM STAT- MEDLINE DCOM- 20110712 LR - 20220310 IS - 1365-2559 (Electronic) IS - 0309-0167 (Print) IS - 0309-0167 (Linking) VI - 58 IP - 3 DP - 2011 Feb TI - HER2 status in gastro-oesophageal adenocarcinomas assessed by two rabbit monoclonal antibodies (SP3 and 4B5) and two in situ hybridization methods (FISH and SISH). PG - 383-94 LID - 10.1111/j.1365-2559.2011.03760.x [doi] AB - AIMS: HER2 gene amplification has been detected in 10-20% of gastric adenocarcinomas. In view of the recently demonstrated clinical benefit of the anti-human epidermal growth factor receptor 2 (HER2) drug trastuzumab in the treatment of advanced gastric cancer, reliable HER2 testing is of key importance. The aim of this study was to examine HER2 status in gastro-oesophageal adenocarcinomas comparing SP3 and 4B5 immunohistochemistry (IHC) with dual probe HER2 [fluorescence in situ hybridization (FISH) and silver in situ hybridization (SISH)]. METHODS AND RESULTS: IHC and SISH were carried out on biopsy specimens of 146 patients with adenocarcinomas of the oesophagus and stomach. All SP3-IHC-positive cases and 91% of 4B5-IHC-positive cases were amplified. Sensitivity of SP3-IHC-positivity and 4B5-IHC-positivity for amplification was 77% and 96%, respectively. Results of FISH performed in 42 cases were identical to SISH. Amplification was heterogeneous in 73% of the adenocarcinomas; 24% of the oesophago-gastric carcinomas and 7% of distal stomach tumours were amplified. CONCLUSIONS: HER2-positivity is present in a significant proportion of oesophago-gastric adenocarcinomas (24%), but at a lower rate in the distal stomach (7%). Sensitivity for amplification is higher with 4B5 IHC than with SP3. FISH and SISH yield identical results, but assessment is much easier with SISH. Our findings provide important guidance for HER2-testing in gastro-oesophageal adenocarcinomas for patients in whom anti-HER2 treatment is considered. CI - (c) 2011 Blackwell Publishing Limited. FAU - Boers, James E AU - Boers JE AD - Department of Pathology, Isala klinieken, Zwolle, the Netherlands. j.e.boers@isala.nl/j.e.boers@me.com FAU - Meeuwissen, Harriette AU - Meeuwissen H FAU - Methorst, Natalie AU - Methorst N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110216 PL - England TA - Histopathology JT - Histopathology JID - 7704136 RN - 0 (Antibodies, Monoclonal) RN - 3M4G523W1G (Silver) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adenocarcinoma/*metabolism/pathology MH - Antibodies, Monoclonal MH - Esophageal Neoplasms/*metabolism/pathology MH - Gene Amplification MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization MH - In Situ Hybridization, Fluorescence MH - Receptor, ErbB-2/genetics/immunology/*metabolism MH - Silver/chemistry MH - Stomach Neoplasms/*metabolism/pathology PMC - PMC3085073 EDAT- 2011/02/18 06:00 MHDA- 2011/07/13 06:00 CRDT- 2011/02/18 06:00 PHST- 2011/02/18 06:00 [entrez] PHST- 2011/02/18 06:00 [pubmed] PHST- 2011/07/13 06:00 [medline] AID - 10.1111/j.1365-2559.2011.03760.x [doi] PST - ppublish SO - Histopathology. 2011 Feb;58(3):383-94. doi: 10.1111/j.1365-2559.2011.03760.x. Epub 2011 Feb 16.