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

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. [ABSTRACT FROM AUTHOR]