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Digital image analysis of HER2 immunohistochemistry in gastric‐ and oesophageal adenocarcinoma: a validation study on biopsies and surgical specimens
Author(s) -
Koopman Timco,
Bock Geertruida H,
Buikema Henk J,
Smits Maria M,
Louwen Maarten,
Hage Mariska,
Imholz Alex L T,
Vegt Bert
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13322
Subject(s) - cish , medicine , immunohistochemistry , gold standard (test) , adenocarcinoma , biopsy , cancer , chromogenic in situ hybridization , pathology , radiology , biology , in situ hybridization , biochemistry , gene expression , gene
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) cut‐offs. 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 cut‐offs) and 85.6% (weighted κ = 0.80, GEC cut‐offs). 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 cut‐offs and 46.5% with GEC cut‐offs. HER2 status was positive in 48 cases (15%) with standard diagnostics and DIA using GEC cut‐offs, and 46 cases (14.4%) using BC cut‐offs (all with CISH in 2+ cases). Considering standard diagnostics as a reference, DIA showed 93.8% sensitivity and 99.6% specificity (BC cut‐offs) or 97.9% sensitivity and 99.6% specificity (GEC cut‐offs). 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.