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Deep Learning Assessment of Tumor Proliferation in Breast Cancer Histological Images

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 نشر من قبل Dayong Wang
 تاريخ النشر 2016
  مجال البحث الهندسة المعلوماتية
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Current analysis of tumor proliferation, the most salient prognostic biomarker for invasive breast cancer, is limited to subjective mitosis counting by pathologists in localized regions of tissue images. This study presents the first data-driven integrative approach to characterize the severity of tumor growth and spread on a categorical and molecular level, utilizing multiple biologically salient deep learning classifiers to develop a comprehensive prognostic model. Our approach achieves pathologist-level performance on three-class categorical tumor severity prediction. It additionally pioneers prediction of molecular expression data from a tissue image, obtaining a Spearmans rank correlation coefficient of 0.60 with ex vivo mean calculated RNA expression. Furthermore, our framework is applied to identify over two hundred unprecedented biomarkers critical to the accurate assessment of tumor proliferation, validating our proposed integrative pipeline as the first to holistically and objectively analyze histopathological images.



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Tumor proliferation is an important biomarker indicative of the prognosis of breast cancer patients. Assessment of tumor proliferation in a clinical setting is highly subjective and labor-intensive task. Previous efforts to automate tumor proliferati on assessment by image analysis only focused on mitosis detection in predefined tumor regions. However, in a real-world scenario, automatic mitosis detection should be performed in whole-slide images (WSIs) and an automatic method should be able to produce a tumor proliferation score given a WSI as input. To address this, we organized the TUmor Proliferation Assessment Challenge 2016 (TUPAC16) on prediction of tumor proliferation scores from WSIs. The challenge dataset consisted of 500 training and 321 testing breast cancer histopathology WSIs. In order to ensure fair and independent evaluation, only the ground truth for the training dataset was provided to the challenge participants. The first task of the challenge was to predict mitotic scores, i.e., to reproduce the manual method of assessing tumor proliferation by a pathologist. The second task was to predict the gene expression based PAM50 proliferation scores from the WSI. The best performing automatic method for the first task achieved a quadratic-weighted Cohens kappa score of $kappa$ = 0.567, 95% CI [0.464, 0.671] between the predicted scores and the ground truth. For the second task, the predictions of the top method had a Spearmans correlation coefficient of r = 0.617, 95% CI [0.581 0.651] with the ground truth. This was the first study that investigated tumor proliferation assessment from WSIs. The achieved results are promising given the difficulty of the tasks and weakly-labelled nature of the ground truth. However, further research is needed to improve the practical utility of image analysis methods for this task.
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