HER2 Scoring in Gastric and Gastroesophageal Junction Adenocarcinoma: Validation of Immunohistochemistry and Silver In Situ Hybridization (SISH).
Pauline C Henry, Eugene T Hsieh, Kevin Kwok, Wedad Hanna. Sunnybrook Health Sciences Centre and University of Toronto, ON, Canada
Background: HER2 amplification has been shown to occur in a subset of gastric and gastroesophageal junction (GEJ) adenocarcinoma. A recent phase III prospective randomized multicenter trial, ToGA (Bang et al, 2010, Lancet 376(9742):659), has demonstrated the efficacy of anti-HER2 therapy with Trastuzumab in advanced gastric adenocarcinoma, in patients with tumour HER2 overexpression by immunohistochemistry (IHC) and amplification by fluorescence in situ hybridization (FISH). As a result, reporting of HER2 status will be clinically indicated in the complete assessment of gastric cancer. IHC and SISH assessment of HER2 status is established in breast cancer, with SISH offering some technical advantages compared to FISH. However, due to differences in scoring criteria from breast cancer, validation of this technique and scoring system is important prior to implementation of routine HER2 IHC and SISH testing in gastric and GEJ cancer.
Design: Consecutive gastric and GEJ formalin-fixed paraffin-embedded biopsy specimens with primary adenocarcinoma were identified from 2009-2010 for this validation study. (Biopsy cases from 1999-2008 have also been identified for inclusion in this ongoing study.) HER2 status was determined by IHC and SISH (Ventana Kits) for all cases with adequate tissue available for analysis, using the HER2 scoring guidelines as applied in the ToGA study.
Results: A total of 51 cases were identified for which 47 had adequate tissue available for analysis (47% intestinal type, 21% diffuse type and 32% mixed morphology). There were 5 (10.6%) SISH positive HER2 amplified cases, 4 of which were scored as IHC positive (3+, 80%) all having intestinal type morphology. One SISH positive case scored as IHC equivocal (2+) also showed intestinal type morphology. The remainder of the IHC 2+ cases (11/47) and all IHC negative (0 or 1+) cases (31/47) were non-HER2 amplified. Only 2/47 cases (4.3%) showed polysomy (CEP17 ≥ 3.0).
Conclusions: Definitive positive and negative gastric HER2 IHC scoring shows excellent agreement with SISH (100%, p<0.00001). HER2 SISH is appropriately indicated for further characterization of HER2 IHC equivocal cases. HER2 IHC overexpression and SISH amplification was seen only in tumors with intestinal morphology in this study. Overall, IHC assessment of HER2 status in gastric and GEJ cancer with the use of SISH for further characterization of equivocal cases is a valid approach for clinical application.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 155, Tuesday Morning