Multi-Institutional Evaluation of Pathologists’ Assessment Compared to Immunoscore
Joseph Willis, Robert A. Anders, Toshihiko Torigoe, Yoshihiko Hirohashi, Carlo Bifulco, Inti Zlobec, Bernhard Mlecnik, Sandra Demaria, Won‐Tak Choi, Pavel Dundr, Fabiana Tatangelo, Annabella Di Mauro, Paméla Baldin, Gabriela Bindea, Florence Marliot, Nacilla Haicheur, Tessa Fredriksen, Amos Kirilovsky, Bénédicte Buttard, Angela Vasaturo, Lucie Lafontaine, Pauline Maby, Carine El Sissy, Assia Hijazi, Amine Majdi, Christine Lagorce, Anne Berger, Marc Van den Eynde, Franck Pagès, Alessandro Lugli, Jérôme Galon
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.