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) 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 CISHpositive 2+ cases. Overall agreement between DIA and consensus manual scores was 76.5% (weighted j = 0.66, BC cut-offs) and 85.6% (weighted j = 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.

Somatostatin Receptor 2 Expression Profiles and Their Correlation with the Efficacy of Somatostatin Analogues in Gastrointestinal Neuroendocrine Tumors

“…Eyeball-based analysis had high sensitivity but low specificity (Figure 4); DIA could be more sensitive and more specific, at least compared to the eyeball-based analysis (Figure 4). Potential application of DIA to the evaluation of human epidermal growth factor receptor 2 (HER2) or programmed death ligand-1 (PDL-1) immunoreactivity was reported to provide a more objective and accurate prediction of therapeutic response than that of eyeball examinations [28,34], which was consistent with this study's results. In addition, evaluation of SSTR2 using DIA may also be useful in predicting the therapeutic efficacy of novel PRRT [21,22] and further studies are warranted to confirm this clinically important aspect.…”

What is the added value of digital image analysis of HER2 immunohistochemistry in breast cancer in clinical practice? A study with multiple platforms

“…DIA of Ki67 IHC in breast carcinoma offers a time‐saving and reproducible alternative to manual counting . Additionally, DIA of HER2 IHC in gastroesophageal adenocarcinomas proved to be a reliable alternative to manual scoring, reducing 2+ cases with high sensitivity (93.8–97.9%) and specificity (99.6%) . However, in comparison to breast carcinoma, HER2 scoring in gastroesophageal carcinoma is prone to more manual 2+ cases due to tumour heterogeneity and a low positivity threshold in biopsies (≥5 tumour cell clusters are sufficient).…”

“…DIA could reduce the number of 2+ cases requiring subsequent ISH testing, which may increase time‐ and cost‐efficiency in clinical practice . Our group previously found that DIA of HER2 IHC can reduce 2+ cases in gastroesophageal adenocarcinoma …”

“…Studies to date have compared manual scoring with DIA by different platforms, each using only one platform . However, interplatform variability may be expected because these platforms use different algorithms, each with unique approaches to classifying tissue and cellular components .…”

Quantitative Image Analysis for Tissue Biomarker Use: A White Paper From the Digital Pathology Association

“…1) have also received CE marking. Visiopharm’s QIA algorithm for HER2 IHC has demonstrated an accurate assessment of both breast carcinoma and gastric/esophageal adenocarcinoma 92,111,112. A recent study demonstrated that employing QIA to score HER2 IHC had excellent concordance with pathologists’ scores and accurately discriminated between HER2 FISH positive and negative cases 113…”