Digital image analysis of HER2 immunohistochemistry in gastric- and oesophageal adenocarcinoma: a validation study on biopsies and surgical specimens
Digital image analysis of HER2 immunohistochemistry in gastric- and oesophageal adenocarcinoma: a validation study on biopsies and surgical specimens
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DOI：
10.1111/his.13322
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发表时间：
2018-01-01
期刊：
影响因子：
6.4
通讯作者：
van der Vegt, Bert
中科院分区：
文献类型：
--
作者：
Koopman, Timco;de Bock, Geertruida H.;van der Vegt, Bert
目的测试结合数字图像分析（DIA）对人表皮生长因子2 （HER2）免疫组织化学（IHC）诊断胃食管腺癌的有效性，作为目前使用手动评分的标准诊断的替代方法。方法和结果我们纳入319例连续胃食管腺癌（232例活检和87例手术标本）。采用标准乳腺癌（BC）和改良胃食管癌（GEC）两种方法，应用DIA确定HER2 IHC分类。协商一致的手工分数是由四位独立观察员建立的。对所有2+病例进行原位显色杂交（CISH），方法为手工评分、DIA或两者同时进行。3+和cish阳性2+的病例认为HER2状态为阳性。DIA和一致手动评分的总体一致性为76.5%（加权= 0.66，BC截止值）和85.6%（加权= 0.80，GEC截止值）。活检和手术标本的一致性相似。所有的歧见都发生在手工IHC模棱两可的病例中。DIA导致2+病例减少：75.8%的BC切断和46.5%的GEC切断。48例（15%）标准诊断和DIA使用GEC切断，46例（14.4%）使用BC切断（2+病例均为CISH）。以标准诊断为参考，DIA的敏感性为93.8%，特异性为99.6% （BC截止值），敏感性为97.9%，特异性为99.6% （GEC截止值）。结论：在胃食管腺癌活检和手术标本中，dia是一种可靠和可行的替代人工HER2 IHC评分的方法，减少了2+例需要进行后续ISH检测的病例。
AimsTo 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 resultsWe 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 = 0.66, BC cut-offs) and 85.6% (weighted = 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).ConclusionsDIA 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.