Marliot Florence, Chen Xiaoyi, Kirilovsky Amos, Sbarrato Thomas, El Sissy Carine, Batista Luciana, Van den Eynde Marc, Haicheur-Adjouri Nacilla, Anitei Maria-Gabriela, Musina Ana-Maria, Scripcariu Viorel, Lagorce-Pagès Christine, Hermitte Fabienne, Galon Jérôme, Fieschi Jacques, Pagès Franck
Laboratory of Integrative Immunology and cancerology, INSERM, University of Paris, Cordeliers Research centre, Immunomonitoring Platform, Laboratory of Immunology, AP-HP (Assistance Publique-Hôpitaux de Paris) Hôpital Européen Georges Pompidou, Paris, France.
Laboratory of Information Sciences to Support Personalized Medicine, Cordeliers Research Centre, Paris, France.
J Immunother Cancer. 2020 May;8(1). doi: 10.1136/jitc-2019-000272.
New and fully validated tests need to be brought into clinical practice to improve the estimation of recurrence risk in patients with colon cancer. The aim of this study was to assess the analytical performances of the Immunoscore (IS) and show its contribution to prognosis prediction.
Immunohistochemical staining of CD3+ and CD8+ T cells on adjacent sections of colon cancer tissues were quantified in the core of the tumor and its invasive margin with dedicated IS modules integrated into digital pathology software. Staining intensity across samples collected between 1989 and 2016 (n=595) was measured. The accuracy of the IS workflow was established by comparing optical and automatic counts. Analytical precision of the IS was evaluated within individual tumor block on distant sections and between eligible blocks. The IS interlaboratory reproducibility (n=100) and overall assay precision were assessed (n=3). Contribution of the IS to prediction of recurrence based on clinical and molecular parameters was determined (n=538).
Optical and automatic counts for CD3+ or CD8+ were strongly correlated (r=0.94, p<0.001 and r=0.92, p<0.001, respectively). CD3 and CD8 staining intensities were not altered by the age of the tumor block over a period of 30 years. Neither the position of tested tissue sections within a tumor block nor the selection of the tissue blocks affected the IS. Reproducibility of the IS was not affected by multiple variables (eg, antibody lots, DAB revelation kits, immunohistochemistry automates and operators). Interassay repeatability of the IS was 100% and interlaboratory reproducibility between two testing centers was 93%. Finally, in a case series of patients with stage II-III colon cancer, the relative proportion of variance for time to recurrence was greatest for the IS (53% of prognostic variability) in a model that included IS, T-stage, microsatellite instability status and total number of lymph nodes.
IS is a robust and validated clinical assay leveraging immune scoring to predict recurrence risk of patient with localized colon cancer. The strong and independent prognostic value of IS should pave the way for it use in clinical practice.
需要将新的且经过充分验证的检测方法应用于临床实践，以改善结肠癌患者复发风险的评估。本研究的目的是评估免疫评分（IS）的分析性能，并展示其对预后预测的贡献。
使用集成到数字病理软件中的专用IS模块，对结肠癌组织相邻切片上的CD3+和CD8+ T细胞进行免疫组织化学染色，并在肿瘤核心及其浸润边缘进行定量分析。测量了1989年至2016年期间收集的样本（n = 595）的染色强度。通过比较光学计数和自动计数来确定IS工作流程的准确性。在单个肿瘤块的远处切片以及符合条件的块之间评估IS的分析精度。评估了IS的实验室间再现性（n = 100）和总体检测精度（n = 3）。确定了IS基于临床和分子参数对复发预测的贡献（n = 538）。
CD3+或CD8+的光学计数和自动计数高度相关（分别为r = 0.94，p < 0.001和r = 0.92，p < 0.001）。在30年的时间里，肿瘤块的年龄并未改变CD3和CD8的染色强度。肿瘤块内测试组织切片的位置以及组织块的选择均未影响IS。IS的再现性不受多种变量（如抗体批次、DAB显色试剂盒、免疫组织化学自动设备和操作人员）的影响。IS的批间重复性为100%，两个检测中心之间的实验室间再现性为93%。最后，在一组II-III期结肠癌患者中，在包含IS、T分期、微卫星不稳定性状态和淋巴结总数的模型中，复发时间的相对方差比例对于IS最大（预后变异性的53%）。
IS是一种强大且经过验证的临床检测方法，利用免疫评分来预测局限性结肠癌患者的复发风险。IS强大且独立的预后价值应为其在临床实践中的应用铺平道路。
