Nuclear shape and orientation features from H&E images predict survival in early-stage estrogen receptor-positive breast cancers.

Nuclear shape and orientation features from H&E images predict survival in early-stage estrogen receptor-positive breast cancers.
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DOI:
10.1038/s41374-018-0095-7
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发表时间:
2018-11
期刊:
Laboratory investigation; a journal of technical methods and pathology
影响因子:
--
通讯作者:
Madabhushi A
Madabhushi A
中科院分区:
其他
文献类型:
--
作者:
Lu C;Romo-Bucheli D;Wang X;Janowczyk A;Ganesan S;Gilmore H;Rimm D;Madabhushi A

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早期雌激素受体阳性 (ER+) 乳腺癌 (BCa) 是美国最常见的 BCa 类型。这些肿瘤的一个关键问题是确定哪些患者将从辅助化疗中获得额外的益处。核多形性(核形状和形态的变异)是乳腺分级方案的重要组成部分,在 ER+ 病例中,分级与疾病结果高度相关。本研究旨在探讨淋巴结阴性(LN−)、ER+ BCa 的苏木精染色和伊红染色组织的数字化图像上计算机提取的核形状和方向的定量图像特征是否可以帮助将患者分为独立的(<10 年短期生存与 >10 年长期生存)结果组,而与标准临床和病理参数无关。我们考虑了由 276 名 ER+、LN- 患者组成的组织微阵列 (TMA) 队列,其中包括 150 名长期总生存患者和 126 名短期总生存患者,其中 177 例随机选择的病例形成模型集,其余 99 例病例作为测试集。使用多分辨率分水岭对单个细胞核进行分割;随后,从每个 TMA 点中提取了 615 个与核形状/纹理和方向紊乱相关的特征。 Wilcoxon 的秩和检验确定了建模集中 15 个最具预后性的定量组织形态特征。随后通过线性判别分析分类器将这些特征组合起来,并在测试集上进行评估,以分配长期与短期疾病特异性生存的概率。在单变量生存分析中,被图像分类器识别为高风险的患者的生存结果明显较差:风险比(95% 置信区间)= 2.91(1.23–6.92),p = 0.02786。控制 T 分期、组织学分级和核分级的多变量分析显示,分类器可以独立预测较差的生存率:风险比(95% 置信区间)= 3.17(0.33–30.46),p = 0.01039。我们的结果表明,核形状和方向的定量组织形态学特征可以强烈且独立地预测 ER+、LN− BCa 患者的生存率。
Early-stage estrogen receptor-positive (ER+) breast cancer (BCa) is the most common type of BCa in the United States. One critical question with these tumors is identifying which patients will receive added benefit from adjuvant chemotherapy. Nuclear pleomorphism (variance in nuclear shape and morphology) is an important constituent of breast grading schemes, and in ER+ cases, the grade is highly correlated with disease outcome. This study aimed to investigate whether quantitative computer-extracted image features of nuclear shape and orientation on digitized images of hematoxylin-stained and eosinstained tissue of lymph node-negative (LN−), ER+ BCa could help stratify patients into discrete (<10 years short-term vs. >10 years long-term survival) outcome groups independent of standard clinical and pathological parameters. We considered a tissue microarray (TMA) cohort of 276 ER+, LN− patients comprising 150 patients with long-term and 126 patients with short-term overall survival, wherein 177 randomly chosen cases formed the modeling set, and 99 remaining cases the test set. Segmentation of individual nuclei was performed using multiresolution watershed; subsequently, 615 features relating to nuclear shape/texture and orientation disorder were extracted from each TMA spot. The Wilcoxon’s rank-sum test identified the 15 most prognostic quantitative histomorphometric features within the modeling set. These features were then subsequently combined via a linear discriminant analysis classifier and evaluated on the test set to assign a probability of long-term vs. short-term disease-specific survival. In univariate survival analysis, patients identified by the image classifier as high risk had significantly poorer survival outcome: hazard ratio (95% confident interval) = 2.91(1.23–6.92), p = 0.02786. Multivariate analysis controlling for T-stage, histology grade, and nuclear grade showed the classifier to be independently predictive of poorer survival: hazard ratio (95% confident interval) = 3.17(0.33–30.46), p = 0.01039. Our results suggest that quantitative histomorphometric features of nuclear shape and orientation are strongly and independently predictive of patient survival in ER+, LN− BCa.
DOI: 10.1117/1.jmi.3.4.047502
发表时间: 2016-10-01
影响因子: 2.4
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发表时间: 2017-10
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DOI: 10.1038/srep33985
发表时间: 2016-10-03
期刊: Scientific reports
影响因子: 4.6
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发表时间: 2016
期刊: Applied immunohistochemistry & molecular morphology : AIMM
影响因子: --
作者:
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