Universidad Nacional de Colombia, Engineering Faculty, Bogotá D.C, Colombia.
Case Western Reserve University, Biomedical Engineering department, Cleveland, OH, USA.
Sci Rep. 2016 Sep 7;6:32706. doi: 10.1038/srep32706.
Early stage estrogen receptor positive (ER+) breast cancer (BCa) treatment is based on the presumed aggressiveness and likelihood of cancer recurrence. Oncotype DX (ODX) and other gene expression tests have allowed for distinguishing the more aggressive ER+ BCa requiring adjuvant chemotherapy from the less aggressive cancers benefiting from hormonal therapy alone. However these tests are expensive, tissue destructive and require specialized facilities. Interestingly BCa grade has been shown to be correlated with the ODX risk score. Unfortunately Bloom-Richardson (BR) grade determined by pathologists can be variable. A constituent category in BR grading is tubule formation. This study aims to develop a deep learning classifier to automatically identify tubule nuclei from whole slide images (WSI) of ER+ BCa, the hypothesis being that the ratio of tubule nuclei to overall number of nuclei (a tubule formation indicator - TFI) correlates with the corresponding ODX risk categories. This correlation was assessed in 7513 fields extracted from 174 WSI. The results suggests that low ODX/BR cases have a larger TFI than high ODX/BR cases (p < 0.01). The low ODX/BR cases also presented a larger TFI than that obtained for the rest of cases (p < 0.05). Finally, the high ODX/BR cases have a significantly smaller TFI than that obtained for the rest of cases (p < 0.01).
早期雌激素受体阳性（ER+）乳腺癌（BCa）的治疗基于对侵袭性和癌症复发可能性的假设。Oncotype DX（ODX）和其他基因表达测试已经能够区分需要辅助化疗的侵袭性 ER+BCa 和仅受益于激素治疗的侵袭性较小的癌症。然而，这些测试昂贵、组织破坏性且需要专门的设施。有趣的是，BCa 分级已被证明与 ODX 风险评分相关。不幸的是，病理学家确定的 Bloom-Richardson (BR) 分级可能存在差异。BR 分级的一个组成类别是小管形成。本研究旨在开发一种深度学习分类器，从 ER+BCa 的全切片图像（WSI）中自动识别小管核，假设小管核与总核数的比例（小管形成指标 - TFI）与相应的 ODX 风险类别相关。在从 174 张 WSI 中提取的 7513 个字段中评估了这种相关性。结果表明，低 ODX/BR 病例的 TFI 大于高 ODX/BR 病例（p<0.01）。低 ODX/BR 病例的 TFI 也大于其余病例的 TFI（p<0.05）。最后，高 ODX/BR 病例的 TFI 明显小于其余病例的 TFI（p<0.01）。
