TY - JOUR
T1 - Intra-tumour heterogeneity is one of the main sources of inter-observer variation in scoring stromal tumour infiltrating lymphocytes in triple negative breast cancer
AU - Kilmartin, Darren
AU - O’Loughlin, Mark
AU - Andreu, Xavier
AU - Bagó-Horváth, Zsuzsanna
AU - Bianchi, Simonetta
AU - Chmielik, Ewa
AU - Cserni, Gábor
AU - Figueiredo, Paulo
AU - Floris, Giuseppe
AU - Foschini, Maria Pia
AU - Kovács, Anikó
AU - Heikkilä, Päivi
AU - Kulka, Janina
AU - Laenkholm, Anne Vibeke
AU - Liepniece-Karele, Inta
AU - Marchiò, Caterina
AU - Provenzano, Elena
AU - Regitnig, Peter
AU - Reiner, Angelika
AU - Ryška, Aleš
AU - Sapino, Anna
AU - Stovgaard, Elisabeth Specht
AU - Quinn, Cecily
AU - Zolota, Vasiliki
AU - Webber, Mark
AU - Roshan, Davood
AU - Glynn, Sharon A.
AU - Callagy, Grace
N1 - Funding Information:
Acknowledgments: Elena Provenzano was supported by the NIHR Cambridge Biomedical Re‐ search Centre (BRC‐1215‐20014). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Giuseppe Floris is recipient of a post‐doctoral mandate from the Klinsche Onderzoek en OpleidingsRaad (KOOR) of the University Hospitals Leuven.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/8/31
Y1 - 2021/8/31
N2 - Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539–0.735, p < 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727–0.864, p < 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561–0.756, p < 0.001) and 40% (ICC 0.644, 95% CI 0.546–0.745, p < 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved.
AB - Stromal tumour infiltrating lymphocytes (sTILs) are a strong prognostic marker in triple negative breast cancer (TNBC). Consistency scoring sTILs is good and was excellent when an internet-based scoring aid developed by the TIL-WG was used to score cases in a reproducibility study. This study aimed to evaluate the reproducibility of sTILs assessment using this scoring aid in cases from routine practice and to explore the potential of the tool to overcome variability in scoring. Twenty-three breast pathologists scored sTILs in digitized slides of 49 TNBC biopsies using the scoring aid. Subsequently, fields of view (FOV) from each case were selected by one pathologist and scored by the group using the tool. Inter-observer agreement was good for absolute sTILs (ICC 0.634, 95% CI 0.539–0.735, p < 0.001) but was poor to fair using binary cutpoints. sTILs heterogeneity was the main contributor to disagreement. When pathologists scored the same FOV from each case, inter-observer agreement was excellent for absolute sTILs (ICC 0.798, 95% CI 0.727–0.864, p < 0.001) and good for the 20% (ICC 0.657, 95% CI 0.561–0.756, p < 0.001) and 40% (ICC 0.644, 95% CI 0.546–0.745, p < 0.001) cutpoints. However, there was a wide range of scores for many cases. Reproducibility scoring sTILs is good when the scoring aid is used. Heterogeneity is the main contributor to variance and will need to be overcome for analytic validity to be achieved.
KW - Breast cancer
KW - International immuno-oncology biomarker working group
KW - Reproducibility
KW - STILs
KW - TILs
KW - Triple negative
UR - http://www.scopus.com/inward/record.url?scp=85114345188&partnerID=8YFLogxK
U2 - 10.3390/cancers13174410
DO - 10.3390/cancers13174410
M3 - Article
AN - SCOPUS:85114345188
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 17
M1 - 4410
ER -
