Tumor Heterogeneity Confounds Lymphocyte Metrics in Diagnostic Lung Cancer Biopsies.

IF 3.7 3区 医学 Q2 MEDICAL LABORATORY TECHNOLOGY
Hedvig Elfving, Viktoria Thurfjell, Johanna Sofia Margareta Mattsson, Max Backman, Carina Strell, Patrick Micke
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Abstract

Context.—: The immune microenvironment is involved in fundamental aspects of tumorigenesis, and immune scores are now being developed for clinical diagnostics.

Objective.—: To evaluate how well small diagnostic biopsies and tissue microarrays (TMAs) reflect immune cell infiltration compared to the whole tumor slide, in tissue from patients with non-small cell lung cancer.

Design.—: A TMA was constructed comprising tissue from surgical resection specimens of 58 patients with non-small cell lung cancer, with available preoperative biopsy material. Whole sections, biopsies, and TMA were stained for the pan-T lymphocyte marker CD3 to determine densities of tumor-infiltrating lymphocytes. Immune cell infiltration was assessed semiquantitatively as well as objectively with a microscopic grid count. For 19 of the cases, RNA sequencing data were available.

Results.—: The semiquantitative comparison of immune cell infiltration between the whole section and the biopsy displayed fair agreement (intraclass correlation coefficient [ICC], 0.29; P = .01; CI, 0.03-0.51). In contrast, the TMA showed substantial agreement compared with the whole slide (ICC, 0.64; P < .001; CI, 0.39-0.79). The grid-based method did not enhance the agreement between the different tissue materials. The comparison of CD3 RNA sequencing data with CD3 cell annotations confirmed the poor representativity of biopsies as well as the stronger correlation for the TMA cores.

Conclusions.—: Although overall lymphocyte infiltration is relatively well represented on TMAs, the representativity in diagnostic lung cancer biopsies is poor. This finding challenges the concept of using biopsies to establish immune scores as prognostic or predictive biomarkers for diagnostic applications.

肿瘤异质性影响肺癌活检诊断中的淋巴细胞指标
背景免疫微环境参与了肿瘤发生的基本环节,目前正在开发用于临床诊断的免疫评分:评估在非小细胞肺癌患者的组织中,与整个肿瘤切片相比,小型诊断性活检和组织芯片(TMA)对免疫细胞浸润的反映程度:构建的 TMA 由 58 名非小细胞肺癌患者的手术切除标本组织和术前活检材料组成。对全切片、活检组织和 TMA 进行泛 T 淋巴细胞标记物 CD3 染色,以确定肿瘤浸润淋巴细胞的密度。对免疫细胞浸润进行半定量评估,并通过显微网格计数进行客观评估。其中19个病例的RNA测序数据可用:整个切片与活检之间免疫细胞浸润的半定量比较显示出相当的一致性(类内相关系数 [ICC],0.29;P = .01;CI,0.03-0.51)。相比之下,与整张切片相比,TMA 显示出很大的一致性(ICC,0.64;P <.001;CI,0.39-0.79)。基于网格的方法并没有提高不同组织材料之间的一致性。CD3 RNA 测序数据与 CD3 细胞注释的比较证实,活检组织的代表性较差,而 TMA 核心的相关性较强:结论:虽然淋巴细胞浸润在 TMA 中的总体表现相对较好,但在诊断性肺癌活检中的代表性较差。这一发现对使用活组织切片建立免疫评分作为诊断应用的预后或预测生物标记物的概念提出了挑战。
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来源期刊
CiteScore
9.20
自引率
2.20%
发文量
369
审稿时长
3-8 weeks
期刊介绍: Welcome to the website of the Archives of Pathology & Laboratory Medicine (APLM). This monthly, peer-reviewed journal of the College of American Pathologists offers global reach and highest measured readership among pathology journals. Published since 1926, ARCHIVES was voted in 2009 the only pathology journal among the top 100 most influential journals of the past 100 years by the BioMedical and Life Sciences Division of the Special Libraries Association. Online access to the full-text and PDF files of APLM articles is free.
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