Digital image analysis of membrane connectivity is a robust measure of HER2 immunostains
Digital image analysis of membrane connectivity is a robust measure of HER2 immunostains
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DOI：
10.1007/s10549-011-1514-2
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发表时间：
2012-02-01
影响因子：
3.8
通讯作者：
Vyberg, Mogens
中科院分区：
文献类型：
--
作者：
Brugmann, Anja;Eld, Mikkel;Vyberg, Mogens
本研究的目的是开发和验证一种新的软件，HER 2-CONNECTTM，用于乳腺癌标本中人表皮生长因子受体2（HER 2）的数字图像分析。该软件基于评价细胞膜连接性的算法评估HER 2的免疫组织化学（IHC）染色反应。对HER 2-CONNECTTM算法进行了调整，以匹配由5名经验丰富的评估员在训练集中进行的HER 2数字图像评分，并在单独的验证集中进行了确认。训练集由167个乳腺癌组织核心图像组成，其中评估者单独且设盲地概述了感兴趣区域，并将其HER 2评分0/1+/2+/3+给予特定肿瘤区域。验证集由86个核心图像组成，其中自动图像分析软件的结果与5名评估员提供的评分相关。对所有核心进行HER 2荧光原位杂交（FISH），并用作参比标准品。图像分析软件和5名评估员的数字评分之间的总体一致性在训练集中为92.1%（Cohen's Kappa：0.859），在验证集中为92.3%（Cohen's Kappa：0.864）。与FISH相关的图像分析敏感性为99.2%，特异性为100%。总之，Visiopharm HER 2 IHC算法HER 2-CONNECTTM可以高准确度区分扩增和非扩增病例，并减少可疑类别，从而提供了一种有前途的补充诊断工具，以提高HER 2评估的一致性。
The purpose of this study was to develop and validate a new software, HER2-CONNECTTM, for digital image analysis of the human epidermal growth factor receptor 2 (HER2) in breast cancer specimens. The software assesses immunohistochemical (IHC) staining reactions of HER2 based on an algorithm evaluating the cell membrane connectivity. The HER2-CONNECTTM algorithm was aligned to match digital image scorings of HER2 performed by 5 experienced assessors in a training set and confirmed in a separate validation set. The training set consisted of 167 breast carcinoma tissue core images in which the assessors individually and blinded outlined regions of interest and gave their HER2 score 0/1+/2+/3+ to the specific tumor region. The validation set consisted of 86 core images where the result of the automated image analysis software was correlated to the scores provided by the 5 assessors. HER2 fluorescence in situ hybridization (FISH) was performed on all cores and used as a reference standard. The overall agreement between the image analysis software and the digital scorings of the 5 assessors was 92.1% (Cohen's Kappa: 0.859) in the training set and 92.3% (Cohen's Kappa: 0.864) in the validation set. The image analysis sensitivity was 99.2% and specificity 100% when correlated to FISH. In conclusion, the Visiopharm HER2 IHC algorithm HER2-CONNECTTM can discriminate between amplified and non-amplified cases with high accuracy and diminish the equivocal category and thereby provides a promising supplementary diagnostic tool to increase consistency in HER2 assessment.