Standardized assessment of tumor-infiltrating lymphocytes in breast cancer: an evaluation of inter-observer agreement between pathologists

Trine Tramm, Tina Di Caterino, Anne-Marie B Jylling, Giedrius Lelkaitis, Anne-Vibeke Lænkholm, Péter Ragó, Tomasz P Tabor, Maj-Lis M Talman, Emmanouela Vouza, Scientific Committee of Pathology, Danish Breast Cancer Group (DBCG)

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INTRODUCTION: In breast cancer, there is a growing body of evidence that tumor-infiltrating lymphocytes (TILs) may have clinical utility and may be able to direct clinical decisions for subgroups of patients. Clinical utility is, however, not sufficient for warranting the implementation of a new biomarker in the routine practice, and evaluation of the analytical validity is needed, including testing the reproducibility of decentralized assessment of TILs. The aim of this study was to evaluate the inter-observer agreement of TILs assessment using a standardized method, as proposed by the International TILs Working Group 2014, applied to a cohort of breast cancers reflecting an average breast cancer population.

MATERIAL AND METHODS: Stromal TILs were assessed using full slide sections from 124 breast cancers with varying histology, malignancy grade and ER- and HER2 status. TILs were estimated by nine dedicated breast pathologists using scanned hematoxylin-eosin stainings. TILs results were categorized using various cutoffs, and the inter-observer agreement was evaluated using the intraclass coefficient (ICC), Kappa statistics as well as individual overall agreements with the median value of TILs.

RESULTS: Evaluation of TILs led to an ICC of 0.71 (95% CI: 0.65-0.77) corresponding to an acceptable agreement. Kappa values were in the range of 0.38-0.46 corresponding to a fair to moderate agreement. The individual agreements increased, when using only two categories ('high' vs. 'low' TILs) and a cutoff of 50-60%.

DISCUSSION: The results of the present study are in accordance with previous studies, and shows that the proposed methodology for standardized evaluation of TILs renders an acceptable inter-observer agreement. The findings, however, indicate that assessment of TILs needs further refinement, and is in support of the latest St. Gallen Consensus, that routine reporting of TILs for early breast cancer is not ready for implementation in a clinical setting.

TidsskriftActa Radiologica Open
Udgave nummer1
Sider (fra-til)90-94
StatusUdgivet - jan. 2018
Begivenhed16th Acta Oncologica Symposium - Aarhus , Danmark
Varighed: 18. jan. 201819. jan. 2018


Konference16th Acta Oncologica Symposium


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