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Anja Høegh Brügmann

Digital image analysis in HER2 immunostained breast carcinomas


 In this study we developed and validated 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.
Methods: 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.
Results: 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 100% and specificity 99,2% when correlated to FISH.
Conclusions: The 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.


Anja Brügmann (1970), MD, PhD
Current position: Resident in Pathology at Aalborg University Hospital.
Research field: Breast cancer, metastatic tumor cell profiling, Human epidermal growth factor receptors and ligands, IHC, FISH, image analysis, tissue microarray, RT-PCR.

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