Biopsy variability of lymphocytic infiltration in breast cancer subtypes and the ImmunoSkew score
Biopsy variability of lymphocytic infiltration in breast cancer subtypes and the ImmunoSkew score
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DOI：
10.1038/srep36231
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发表时间：
2016-11-04
影响因子：
4.6
通讯作者：
Yuan, Yinyin
中科院分区：
文献类型：
--
作者：
Khan, Adnan Mujahid;Yuan, Yinyin
肿瘤活检的数量需要一个良好的肿瘤代表一直存在争议。需要考虑的一个重要因素是肿瘤内的异质性，它可能因癌症类型和亚型而异。特别是免疫细胞经常表现出复杂的浸润模式，然而，对免疫细胞的空间异质性以及人类肿瘤的这种基本生物学性质如何影响活检变异性和治疗耐药性缺乏定量了解。我们使用一种新的虚拟活检方法系统地研究了998例乳腺肿瘤中淋巴细胞浸润的活检变异性。在所有乳腺癌中，我们观察到随着活检次数的增加，活检和淋巴细胞浸润的全肿瘤评分之间的一致性呈非线性增加，但超过四次活检几乎没有改善。有趣的是，淋巴细胞浸润的活检变异性在乳腺癌亚型中差异很大，人类表皮生长因子受体2阳性（HER2+）亚型的变异性最高。随后，我们确定了一种空间变异性的定量测量方法，该方法可以预测HER2+亚型独立于标准临床变量（淋巴结状态、肿瘤大小和分级）的疾病特异性生存。我们的研究展示了系统方法如何提供新的见解，可以影响基于肿瘤异质性定量知识的未来研究设计。
The number of tumour biopsies required for a good representation of tumours has been controversial. An important factor to consider is intra-tumour heterogeneity, which can vary among cancer types and subtypes. Immune cells in particular often display complex infiltrative patterns, however, there is a lack of quantitative understanding of the spatial heterogeneity of immune cells and how this fundamental biological nature of human tumours influences biopsy variability and treatment resistance. We systematically investigate biopsy variability for the lymphocytic infiltrate in 998 breast tumours using a novel virtual biopsy method. Across all breast cancers, we observe a nonlinear increase in concordance between the biopsy and whole-tumour score of lymphocytic infiltrate with increasing number of biopsies, yet little improvement is gained with more than four biopsies. Interestingly, biopsy variability of lymphocytic infiltrate differs considerably among breast cancer subtypes, with the human epidermal growth factor receptor 2-positive (HER2+) subtype having the highest variability. We subsequently identify a quantitative measure of spatial variability that predicts disease-specific survival in HER2+ subtype independent of standard clinical variables (node status, tumour size and grade). Our study demonstrates how systematic methods provide new insights that can influence future study design based on a quantitative knowledge of tumour heterogeneity.