Digital image analysis of HER2 immunohistochemistry in gastric- and oesophageal adenocarcinoma: a validation study on biopsies and surgical specimens

Abstract

Aims

to test the validity of diagnostics incorporating digital image analysis (DIA) for human epidermal growth factor 2 (HER2) immunohistochemistry (IHC) in gastro-oesophageal adenocarcinomas, as an alternative to current standard diagnostics using manual scoring.

Methods and results

we included 319 consecutive gastro-oesophageal adenocarcinomas (232 biopsies and 87 surgical specimens). DIA was applied to determine HER2 IHC classification, using both standard breast cancer (BC) and modified gastro-oesophageal cancer (GEC) cutoffs. Consensus manual scores were established by four independent observers. Chromogenic in situ hybridization (CISH) was performed on all 2+ cases by manual scoring, DIA or both. HER2 status was considered positive in 3+ and CISH positive 2+ cases. Overall agreement between DIA and consensus manual scores was 76.5% (weighted κ=0.66, BC cutoffs) and 85.6% (weighted κ=0.80, GEC cutoffs). Agreement was similar for biopsies and surgical specimens. All disagreement occurred in the manual IHC equivocal cases. DIA resulted in a reduction of 2+ cases: 75.8% with BC cutoffs and 46.5% with GEC cutoffs. HER2 status was positive in 48 cases (15%) with standard diagnostics and DIA using GEC cutoffs, and 46 cases (14.4%) using BC cutoffs (all with CISH in 2+ cases). Considering standard diagnostics as a reference, DIA showed 93.8% sensitivity and 99.6% specificity (BC cutoffs) or 97.9% sensitivity and 99.6% specificity (GEC cutoffs).

Conclusions

DIA is a reliable and feasible alternative to manual HER2 IHC scoring in gastro-oesophageal adenocarcinoma, both in biopsies and surgical specimens, leading to a reduction of 2+ cases for which subsequent ISH testing is required.

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