Interobserver reproducibility of tumor-infiltrating lymphocyte evaluations in breast cancer

Tumor-infiltrating lymphocytes (TILs) have a prognostic value in breast cancer (BC); however, because of the lack of standard evaluation methods, we aimed to assess the interobserver agreement of stromal TILs (sTILs) and intratumoral TILs (iTILs) as well as the effect of hot spot areas and molecular subtyping on the overall agreement.

The study consisted of 121 haematoxylin and eosin (H and E)-stained slides of invasive BC samples obtained from the pathology archives. The TIL assessment was based on the International TIL Working Group recommendations for the percentage of sTILs and was conducted by four pathologists. The percentage of iTILs, the number of lymphocytes in hot spot areas (iTILs-HS), and the overall interobserver agreement for the molecular subtypes were evaluated. The interclass correlation coefficient (ICC) was used to assess interobserver agreement among the four pathologists.

The ICC score among the observers for the sTIL percentages was 0.74, and the individual ICC values for each molecular subtype were 0.55, 0.88, and 0.79 for luminal, HER2-positive, and triple-negative tumors, respectively. The compliance value for the iTILs was 0.29 (95% confidence interval (CI) = 0.06-0.48], whereas the compliance value for the iTILs-HS was 0.63 (95% CI = 0.49-0.71). The compliance values for the iTILs-HS subtypes were 0.72, 0.43, and 0.55 for luminal, HER2-positive, and triple-negative tumors, respectively.

The IWTILG recommendations are reproducible and reliable. The interobserver agreement of the sTIL percentages was considerably higher for the triple-negative and HER2-positive cases than the luminal cases, whereas the interobserver agreement for the assessment of iTILs-HS in tumors was higher for the luminal subtype.