Willis Joseph, Anders Robert A, Torigoe Toshihiko, Hirohashi Yoshihiko, Bifulco Carlo, Zlobec Inti, Mlecnik Bernhard, Demaria Sandra, Choi Won-Tak, Dundr Pavel, Tatangelo Fabiana, Di Mauro Annabella, Baldin Pamela, Bindea Gabriela, Marliot Florence, Haicheur Nacilla, Fredriksen Tessa, Kirilovsky Amos, Buttard Bénédicte, Vasaturo Angela, Lafontaine Lucie, Maby Pauline, El Sissy Carine, Hijazi Assia, Majdi Amine, Lagorce Christine, Berger Anne, Van den Eynde Marc, Pagès Franck, Lugli Alessandro, Galon Jérôme
Department of Pathology, UH Cleveland Medical Center, Cleveland, OH 44106, USA.
Pathology Department, John Hopkins, Baltimore, MD 21287, USA.
Cancers (Basel). 2023 Aug 10;15(16):4045. doi: 10.3390/cancers15164045.
The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists' visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification.
An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases. Concordance between pathologists' T-score, corresponding hematoxylin-eosin (H&E) slides, and the digital IS was evaluated for two- and three-category IS.
Non-concordant T-scores were reported in more than 92% of cases. Disagreement between semi-quantitative visual assessment of T-score and the reference IS was observed in 91% and 96% of cases before and after training, respectively. Statistical analyses showed that the concordance index between pathologists and the digital IS was weak in two- and three-category IS, respectively. After training, 42% of cases had a change in T-score, but no improvement was observed with a Kappa of 0.465 and 0.374. For the 20% of patients around the cut points, no concordance was observed between pathologists and digital pathology analysis in both two- and three-category IS, before or after training (all Kappa < 0.12).
The standardized IS assay outperformed expert pathologists' T-score evaluation in the clinical setting. This study demonstrates that digital pathology, in particular digital IS, represents a novel generation of immune pathology tools for reproducible and quantitative assessment of tumor-infiltrated immune cell subtypes.
免疫评分（IS）是一种定量数字病理学检测方法，用于评估癌症患者的免疫反应。本研究报告了与IS定量相比，病理学家对CD3 +和CD8 +染色的结肠肿瘤进行视觉评估的可重复性。
一个国际专家病理学家小组评估了从270例随机选择的结肠癌（CC）病例中获取的540张图像。针对两类和三类IS，评估了病理学家的T评分、相应的苏木精-伊红（H&E）切片和数字IS之间的一致性。
超过92%的病例报告了不一致的T评分。在训练前后，分别有91%和96%的病例观察到T评分的半定量视觉评估与参考IS之间存在差异。统计分析表明，在两类和三类IS中，病理学家与数字IS之间的一致性指数分别较弱。训练后，42%的病例T评分发生了变化，但卡方值分别为0.465和0.374，未观察到改善。对于切点周围20%的患者，在两类和三类IS中，训练前后病理学家与数字病理学分析之间均未观察到一致性（所有卡方值<0.12）。
在临床环境中，标准化的IS检测优于专家病理学家的T评分评估。本研究表明，数字病理学，尤其是数字IS，代表了新一代用于可重复和定量评估肿瘤浸润免疫细胞亚型的免疫病理学工具。
