Inter-observer agreement of tumor infiltrating lymphocytes in primary HER2-positive breast cancer and correlation between tissue microarray and full tumor-sections

Frances Mary Reznitsky*, Jeanette Dupont Jensen, Ann Knoop, Anne-Vibeke Laenkholm

*Corresponding author for this work

Abstract

Tumor infiltrating lymphocytes (TILs) have predictive and prognostic potential in HER2-positive breast cancer (HER2 + BC). Due to tumor heterogeneity, guidelines recommend evaluation on full tumor-sections over biopsies, but aren't clear regarding tissue microarrays (TMAs). Herein, we investigate the inter-observer agreement of TILs assessment in HER2 + BC on full-sections and TMAs using a standardized method. Two pathologists assessed TILs using HE full-sections and TMAs from 244 patients with HER2 + BC. TILs were assessed in 10% intervals; values <10% evaluated as 0%, 1% or 5%. Levels of agreement were evaluated using intraclass-coefficient (ICC), Kappa statistics and concordance analysis. For inter-observer agreement for full-sections, ICC was 0.93 (95% CI 0.89-0.95) and Kappa was 0.75, corresponding to acceptable and moderate agreement respectively. For TMAs, ICC was 0.73 (95% CI: 0.62-0.81) and Kappa 0.33, corresponding to unacceptable agreement. For association in matched TMA and full-sections, ICC was 0.64 (95% CI 0.55-0.71) and Lin's concordance correlation coefficient was 0.63 (95% CI 0.55-0.71), corresponding to unacceptable agreement. There is acceptable inter-observer agreement of TILs assessment on full-sections but not TMAs and discrepancy between full-sections and TMAs. TMA preparation must include consideration for representation of both entire tumor area and tumor-microenvironment to correctly define prognostic and predictive values of potential immuno-related biomarkers.

Original languageEnglish
JournalAPMIS - Journal of Pathology, Microbiology and Immunology
Volume130
Issue number9
Pages (from-to)545-550
Number of pages6
ISSN0903-4641
DOIs
Publication statusPublished - Sep 2022

Keywords

  • Biomarkers, Tumor/analysis
  • Breast Neoplasms/diagnosis
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating/pathology
  • Observer Variation
  • Pathologists
  • Prognosis
  • Receptor, ErbB-2/analysis
  • Tumor Microenvironment
  • inter-observer agreement
  • full-sections
  • TMA
  • HER2-positive breast cancer
  • tumor infiltrating lymphocytes

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