A Robust Computer-Aided Approach for Scoring and Quantitative Evaluation of Whole Slide Digital Images of HER2 Immunohistochemistry in Breast Cancer


HER2 is recognized as an essential prognostic parameter in breast cancer. Usually interpretation of HER2 negative cases which has no membrane staining or has faint and weak incomplete cells and also positive cases (3+) that consist of strong and complete cell are easy but cells with moderate and weak HER2 staining (2+ or equivocal) require further analysis with fluorescence in situ hybridization (FISH) technique which is expensive and time consuming. In order to minimize the number of equivocal 2+ cases, we presented an automated approach for scoring HER2 in whole slide images (WSI) which would reduce the number of cases that need to be further processed by the FISH method. This approach is based on morphological techniques which discriminate between amplified and nonamplified cases with high accuracy and decreases the equivocal cases. Experimental results on real datasets demonstrate the wide applicability and high accuracy of our approach in validating of IHC analysis in WSI.

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Digital pathology, HER2, Immunohistology, Computer-aided diagnosis, Whole-slide imaging.

Quantitative output variables

The detailed results correspond to an almost perfect agreement between visual IHC and automated image analysis which allows us to simplify the comparison as indicated in TABLE 1. Among the 300 ROI, the 140 (46%) slides were evaluated as IHC negative (score 0/1+) by the proposed method, however, 127 (42%) slides evaluated as IHC negative by visual IHC whereas all FISH tests were negative. Among 50 equivocal cases which are scored 2+ by visual IHC, 24 of them are categorized as 0/1+ and 3+ by the proposed method. In 26 (8%) cases both approaches agreed in equivocal cases (score 2+). All the 123 (41%) cases which considered as 3+ cases by the pathologist are also positive in our method and the FISH results were also positive. Furthermore, 11 (3%) slides with positive FISH scores are counted as positive cases which are evaluated as equivocal cases in pathologist visual scoring. By the presented method only 26 slides should be further analyzed by the FISH test. Cohon's kappa is 0.86, that shows a good agreement between visual IHC and the proposed method.


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