Abstract 4069: Evaluation of inflammatory infiltration (tumor infiltrating lymphocytes - TIL) in malignant melanoma
Authors: Nemejcova Kristyna , Ticha Ivana , Kodet Ondrej , Dura Miroslav , Bartu Michaela , Dundr Pavel 
Published: August 2018

Abstract
Assessment of tumor infiltrating lymphocytes (TIL) in malignant melanoma (MM) should be a standard part of biopsy examination. This parameter is of interest regarding its prognostic, but potentially also predictive significance. However, the usefulness of this marker in routine practice is limited due to unequal methodological approach and equivocal results of previous studies. The aim of our study is to compare 5 different methods of TIL assessment with respect to their prognostic significance.
TIL were double-blindly evaluated by two pathologists in 221 cases of primary cutaneous malignant melanoma. The sample set comprised of pT1 - 48 cases, pT2 - 61 cases, pT3 - 69 cases, and pT4 - 43 cases. Five different scoring methods were used, including: i) Clark scoring; ii) Melanoma Institute Australia (MIA) system; iii) scoring system used in the study of Saldanha et al.; iv) scoring system used in the TCGA study and modified by Park et al.; v) the system recently proposed by “International Immuno-Oncology Biomarker Working Group“ for TIL scoring in all solid tumors. Cox's Proportional Hazard Method was used to test 10-year survival with three main outcomes - disease-specific survival (DFS), local recurrence-free survival (LFS), and distant metastasis-free survival (MFS).
The evaluation of TIL with respect to its prognostic value was statistically significant for all 3 outcomes when using Clark scoring (score 0, 1 vs. score 2; DFS p=0.027, LFS p=0.019, and MFS p=0.010); MIA system (groups 0, 1 vs. groups 2, 3; DFS p=0.060, LFS p=0.035, and MFS p=0.012) and the system proposed by “International Immuno-Oncology Biomarker Working Group“. In this system, however, only the assessment of stromal TIL (not intratumoral or in the invasive margin) showed prognostic significance (DFS p=0.034, LFS p=0.033, and MFS p=0.033). Our results did not prove prognostic significance of the scoring systems used in the study published by Saldanha et al. and Park et al.
In conclusion, the results of our study showed that the evaluation of TIL in MM is a prognostic marker, but its significance is dependent on the chosen scoring method. From a practical point of view, application of a unified methodology is desirable. This would allow for a comparison across studies, and, even more interestingly, also for the assessment of the predictive value of TIL evaluation, especially with respect to immunotherapy. However, out of the five different methods used in our study, only 3 showed statistically significant results and none of the 3 systems seem to be superior to others.
This work was supported by Ministry of Health, Czech Republic (Conceptual development of research organization 64165, General University Hospital in Prague, and by project AZV 16-30954A).
Citation Format: Kristyna Nemejcova, Ivana Ticha, Ondrej Kodet, Miroslav Dura, Michaela Bartu, Pavel Dundr. Evaluation of inflammatory infiltration (tumor infiltrating lymphocytes - TIL) in malignant melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4069.