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评估乳腺癌中的 TIL(肿瘤浸润淋巴细胞):结合免疫组化与基因表达分析优化评分的建议

英文原题:Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring.

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Assessing Tumor-Infiltrating Lymphocytes in Breast Cancer: A Proposal for Combining Immunohistochemistry and Gene Expression Analysis to Refine Scoring.

PubMed 2022/02/11(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

乳腺癌标本中TIL(肿瘤浸润淋巴细胞)(TILs)的评分日益受到关注,因为TILs在HER2+和三阴性乳腺癌中具有预后和预测价值。

我们评估了通过肉眼观察苏木精-伊红染色组织切片对TILs进行评分时的评分者内和评分者间变异性。我们进一步探讨了对这些切片进行免疫细胞表面标志物CD45、CD3、CD4和CD8的免疫组化染色,并结合nanoString nCounter基因表达分析,是否能够优化TIL评分。研究纳入了12例女性、未经治疗的乳腺癌患者的福尔马林固定石蜡包埋和新鲜冷冻空芯针活检标本。TILs评分由三名独立病理学家完成两次,洗脱期为3天。随着TIL数量的增加,评分者内和评分者间变异性也随之增大。在CD3和CD8染色的组织切片上观察到最高的可重复性。后者的TIL评分与通过nanoString nCounter基因表达分析获得的TIL评分相关性良好。基因表达分析还揭示了104个和62个分别与两种TIL评分呈正相关和负相关的基因。

总之,整合免疫组化和基因表达分析是优化乳腺肿瘤TIL评分的一种有价值的策略。

展开英文摘要原文

Scoring of tumor-infiltrating lymphocytes (TILs) in breast cancer specimens has gained increasing attention, as TILs have prognostic and predictive value in HER2 + and triple-negative breast cancer.

We evaluated the intra- and interrater variability when scoring TILs by visual inspection of hematoxylin and eosin-stained tissue sections.

We further addressed whether immunohistochemical staining of these sections for immune cell surface markers CD45, CD3, CD4, and CD8 and combination with nanoString nCounter gene expression analysis could refine TIL scoring. Formalin-fixed paraffin-embedded and fresh-frozen core needle biopsies of 12 female and treatment-naive breast cancer patients were included. Scoring of TILs was performed twice by three independent pathologists with a washout period of 3 days.

Increasing intra- and interrater variability was observed with higher TIL numbers. The highest reproducibility was observed on tissue sections stained for CD3 and CD8. The latter TIL scores correlated well with the TIL scores obtained through nanoString nCounter gene expression analysis. Gene expression analysis also revealed 104 and 62 genes that are positively and negatively related to both TIL scores.

In conclusion, integration of immunohistochemistry and gene expression analysis is a valuable strategy to refine TIL scoring in breast tumors.

论文信息

作者
Locy H、Verhulst S、Cools W、Waelput W、Brock S、Cras L、Schiettecatte A、Jonckheere J
单位
Laboratory for Molecular and Cellular Therapy, Department of Biomedical Sciences (BMWE), Vrije Universiteit Brussel (VUB), Brussels, Belgium.Belgium
文献类型
非美国政府资助研究
期刊
Frontiers in immunology2022
原文标识
PubMed 35222378 · DOI 10.3389/fimmu.2022.794175