Intra-tumour heterogeneity is one of the main sources of inter-observer variation in scoring stromal tumour infiltrating lymphocytes in triple negative breast cancer

Darren Kilmartin, Mark O’Loughlin, Xavier Andreu, Zsuzsanna Bagó-Horváth, Simonetta Bianchi, Ewa Chmielik, Gábor Cserni, Paulo Figueiredo, Giuseppe Floris, Maria Pia Foschini, Anikó Kovács, Päivi Heikkilä, Janina Kulka, Anne Vibeke Laenkholm, Inta Liepniece-Karele, Caterina Marchiò, Elena Provenzano, Peter Regitnig, Angelika Reiner, Aleš RyškaAnna Sapino, Elisabeth Specht Stovgaard, Cecily Quinn, Vasiliki Zolota, Mark Webber, Davood Roshan, Sharon A. Glynn, Grace Callagy

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
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Abstract

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.

Original languageEnglish
Article number4410
Number of pages16
JournalCancers
Volume13
Issue number17
DOIs
Publication statusPublished - 31 Aug 2021

Keywords*

  • Breast cancer
  • International immuno-oncology biomarker working group
  • Reproducibility
  • STILs
  • TILs
  • Triple negative

Field of Science*

  • 3.1 Basic medicine
  • 3.2 Clinical medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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