HER2 status in gastroesophageal adenocarcinomas assessed by two rabbit monoclonal antibodies (SP3 and 4B5) and two in situ hybridisation methods (FISH and SISH)

James Evan Boers (1) , Harriette Meeuwissen (2) , Natalie Methorst (2)

1 pathology
2 Pathology

Introduction HER2 gene amplification has been detected in 10% - 20% in gastric adenocarcinomas. In view of the recently demonstrated clinical benefit of the anti-HER2 drug trastuzumab in the treatment of advanced gastric cancer, reliable HER2 testing is of key importance. Aim To examine HER2 status in gastro-esophageal adenocarcinomas comparing SP3 and 4B5 immunohistochemistry (IHC) with dual probe HER2 (FISH and SISH). Methods and results IHC and SISH was carried out on biopsies of 146 patients with adenocarcinomas of the esophagus 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 esophagogastric carcinomas and 7% of distal stomach tumours were amplified. Conclusions HER2-positivity is present in a significant proportion of esophago-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 gastroesophageal adenocarcinomas for patients where anti-HER2 treatment is considered.

Mots clés: Medicine

James Evan Boers, Harriette Meeuwissen, Natalie Methorst. HER2 status in gastroesophageal adenocarcinomas assessed by two rabbit monoclonal antibodies (SP3 and 4B5) and two in situ hybridisation methods (FISH and SISH). Histopathology, 2011, 58 (3), pp.383. ⟨10.1111/j.1365-2559.2011.03760.x⟩. ⟨hal-00614750⟩