The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma

The adequacy of tissue microarrays in the assessment of inter- and intra-tumoural heterogeneity of infiltrating lymphocyte burden in leiomyosarcoma
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DOI:
10.1038/s41598-019-50888-5
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发表时间:
2019-10-10
期刊:
影响因子:
4.6
通讯作者:
Huang, P. H.
Huang, P. H.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lee, A. T. J.;Chew, W.;Huang, P. H.

文献摘要

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平滑肌肉瘤(LMS)是软组织肉瘤的一种亚型,具有组织学异质性,其肿瘤浸润淋巴细胞(til)的特征和临床相关性尚未确定。组织微阵列(TMA)在分析TIL负担的研究中是有吸引力的,但考虑到肿瘤内异质性可能引入采样误差,这种方法的充分性尚不确定。在这项研究中,我们评估了原发性LMS标本回顾性队列中TIL负担的组织学间和肿瘤内异质性。使用虚拟TMA方法,我们还分析了在整个组织切片中准确表示TIL负担所需的TMA核的最佳数量。研究发现,LMS的TIL负担普遍较低,且在空间上呈同质性,尽管一小部分LMS的TIL水平较高,且分布异质性更强。我们表明,需要一个常规和实用的数字(例如= 11)来准确估计绝对TIL数。我们的发现为未来研究的设计提供了一个基准,旨在确定LMS和其他肉瘤亚型的免疫微环境的临床相关性。
The characterisation and clinical relevance of tumour-infiltrating lymphocytes (TILs) in leiomyosarcoma (LMS), a subtype of soft tissue sarcoma that exhibits histological heterogeneity, is not established. The use of tissue microarrays (TMA) in studies that profile TIL burden is attractive but given the potential for intra-tumoural heterogeneity to introduce sampling errors, the adequacy of this approach is undetermined. In this study, we assessed the histological inter- and intra-tumoural heterogeneity in TIL burden within a retrospective cohort of primary LMS specimens. Using a virtual TMA approach, we also analysed the optimal number of TMA cores required to provide an accurate representation of TIL burden in a full tissue section. We establish that LMS have generally low and spatially homogenous TIL burdens, although a small proportion exhibit higher levels and more heterogeneous distribution of TILs. We show that a conventional and practical number (e.g. = 11) are required to accurately estimate absolute TIL numbers. Our findings provide a benchmark for the design of future studies aiming to define the clinical relevance of the immune microenvironments of LMS and other sarcoma subtypes.