Correlation of tumor infiltrating lymphocytes in invasive breast carcinomas: a morphological study
DOI:
https://doi.org/10.18203/2320-6012.ijrms20262186Keywords:
Tumour infiltrating lymphocytes, Invasive breast cancer, PrognosisAbstract
Background: The aim of the study is to analyse the stromal tumor-infiltrating lymphocytes (sTILs) in invasive breast carcinomas and assess the percentage of sTILs in invasive breast carcinomas using a single H and E slide following a standardized protocol. Also, to study the correlation between sTILs and known prognostic factors.
Methods: Two year retrospective study of 190 cases using a single representative H and E slide examined by 2 observers. TILs assessed based on current recommendations from the 2014 International TILs Working Group (ITWG) for the evaluation of TILs. Histological type, histological grade, molecular subtypes using relevant IHC markers, number of lymph nodes isolated, number of lymph nodes positive with extracapsular invasion, lymphovascular invasion, perineural invasion, TNM stage and tils in percentage were documented.
Results: The collected data was analysed with IBM SPSS statistics for Windows, version 23.0. Correlation of TILS with age, SBR grade, ER, PR, Ki67, molecular subtype-showed statistical significance with an acceptable p value.
Conclusions: Many studies have supported the evidence of TILS, in different levels and density which is predictive of response to neoadjuvant chemotherapy. In certain breast carcinoma subtypes, it has a prognostic value in patients treated with adjuvant chemotherapy. From our study TILs show a correlation with few of the known prognostic factors. There is a paucity of data in Indian literature on TILs and its implications. Understanding of the role of TILs regarding could be of importance in devising novel immunotherapeutic strategies in breast cancer treatment.
References
Savas P, Salgado R, Denkert C, Sotiriou C, Darcy PK, Smyth MJ, et al. Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nature Rev Clin Oncol. 2016;13(4):228-41.
Pujani M, Jain H, Chauhan V, Agarwal C, Singh K, Singh M. Evaluation of Tumor infiltrating lymphocytes in breast carcinoma and their correlation with molecular subtypes, tumor grade and stage. Breast Dis. 2020;39(2):619.
Kojima YA, Wang X, Sun H, Compton F, Covinsky M, Zhang S. Reproducible evaluation of tumor-infiltrating lymphocytes (TILs) using the recommendations of International TILs Working Group 2014. Ann Diagnost Pathol. 2018;35:77-9.
Buisseret L, Garaud S, de Wind A, Van den Eynden G, Boisson A, Solinas C, et al. Tumor infiltrating lymphocyte composition, organization and PD-1/PD-L1 expression are linked in breast cancer. Oncoimmunology. 2017;6(1):e1257452.
Ravelli A, Roviello G, Cretella D, Cavazzoni A, Biondi A, Cappelletti MR, Zanotti L, Ferrero G, Ungari M, Zanconati F, Bottini A. Tumor-infiltrating lymphocytes and breast cancer: beyond the prognostic and predictive utility. Tumor Biol. 2017;39(4):1010428317695023.
Bhatia A, Kumar Y. Tumour infiltrating lymphocytes: Changing trends. Clin Oncol. 2018;3:1409.
Al-Attar A, Shehata M, Durrant L, Moseley P, Deen S, Chan S. T cell density and location can influence the prognosis of ovarian cancer. Pathol Oncol Res. 2010;16:361-70.
Wahlin BE, Sander B, Christensson B, Kimby E. CD8+ T-cell content in diagnostic lymph nodes measured by flow cytometry is a predictor of survival in follicular lymphoma. Clin Cancer Res. 2007;13(2):388-97.
Loi S, Drubay D, Adams S, Pruneri G, Francis PA, Lacroix-Triki M, et al. Tumor-infiltrating lymphocytes and prognosis: a pooled individual patient analysis of early-stage triple-negative breast cancers. J Clin Oncol. 2019;37(7):559-69.
Swisher SK, Wu Y, Castaneda CA, Lyons GR, Yang F, Tapia C, et al. Interobserver agreement between pathologists assessing tumor-infiltrating lymphocytes (TILs) in breast cancer using methodology proposed by the International TILs Working Group. Ann Surg Oncol. 2016;23:2242-8.
Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26(2):259-71.
Kolarov-Bjelobrk I, Ivkovic-Kapicl T, Jovanovic D, Trifunovic J, Radic J, Vidovic V. Clinical relevance of determination of tumour infiltrating lymphocytes in breast carcinoma. West Indian Med J. 2017;NA.
West NR, Milne K, Truong PT, Macpherson N, Nelson BH, Watson PH. Tumor infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Res. 2011;13:1-3.
Loi S, Sirtaine N, Piette F, Salgado R, Viale G, Van Eenoo F, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol. 2013;31(7):860-7.
Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40-50.
Adams S, Robert JG, Sandra D, Lori G, Edith AP, Lawrence NS, et al. Prognostic value of tumor-infiltrating lymphocytes in triple negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959-66.
Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, Kronenwett R, et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015;33(9):983-91.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA: a cancer journal for clinicians. 2005;55(2):74-108.
Armstrong A, Dermime S. Developing effective cancer vaccines:design and monitoring are critical. Br J Cancer. 2001;84:1433-6.
Sato E, Olson SH, Ahn J, Bundy B, Nishikawa H, Qian F, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proceedings National Academy Sci. 2005;102(51):18538-43.
Heppner BI, Loibl S, Denkert C. Tumor-infiltrating lymphocytes: a promising biomarker in breast cancer. Breast Care. 2016;11(2):96-100.
Jang N, Kwon HJ, Park MH, Kang SH, Bae YK. Prognostic value of tumor-infiltrating lymphocyte density assessed using a standardized method based on molecular subtypes and adjuvant chemotherapy in invasive breast cancer. Ann Surgical Oncol. 2018;25(4):937-46.
Aaltomaa S, Lipponen P, Eskelinen M, Kosma VM, Marin S, Alhava E, Syrjänen K. Lymphocyte infiltrates as a prognostic variable in female breast cancer. Europ J Can. 1992;28(4-5):859-64.
Tsang J, Hui W, Ni B, Chan K, Yamaguchi R, Kwong A, et al. Lymphocytic infiltrate is associated with favourable biomarkers profile in HER2- overexpressing breast cancers and adverse biomarker profile in ERpositive breast cancers, Breast Cancer Res Treat. 2014;143:1-9.
Jang N, Kwon HJ, Park MH, Kang SH, Bae YK. Prognostic value of tumor Infiltrating lymphocyte density assessed using a standardized method based on molecular subtypes and adjuvant chemotherapy in invasive breast cancer. Ann Surgical Oncol. 2018;25(4):937-46.
Khoury T, Peng X, Yan L, Wang D, Nagrale V. Tumor-Infiltrating Lymphocytes in Breast Cancer: Evaluating Interobserver Variability, Heterogeneity, and Fidelity of Scoring Core Biopsies. Am J Clin Pathol. 2018;150(5):441-50.
Kos Z, Roblin E, Kim RS, Michiels S, Gallas BD, Chen W, et al. Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer. NPJ Breast Cancer. 2020;6(1):1-6.
Nikolaidi A, Kotoula V, Koliou GA, Giannoulatou E, Papadopoulou K, Zagouri F, et al. Tumor Mutational Patterns and Infiltrating Lymphocyte Density in Young and Elderly Patients with Breast Cancer. Cancer Genom Proteom. 2020;17(2):181-93.
Lee HJ, Park IA, Song IH, Shin SJ, Kim JY, Yu JH, et al. Tertiary lymphoid structures: prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer. J Clin Pathol. 2016;69(5):422-30.
Liu JY, Yang GF, Chen FF, Peng CW. Evaluating the prognostic significance of tumor-infiltrating lymphocytes in solid tumor: practice of a standardized method from the International Immuno-Oncology Biomarkers Working Group. Cancer Management Res. 2019;11:6815.
Dieci MV, Radosevic-Robin N, Fineberg S, Van den Eynden G, Ternes N, Penault-Llorca F, et al. Update on tumor-infiltrating lymphocytes (TILs) in breast cancer, including recommendations to assess TILs in residual disease after neoadjuvant therapy and in carcinoma in situ: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer. In Seminars in cancer biology. Academic Press. 2018;52:16-25.
Watanabe T, Hida AI, Inoue N, Imamura M, Fujimoto Y, Akazawa K, et al. Abundant tumor infiltrating lymphocytes after primary systemic chemotherapy predicts poor prognosis in estrogen receptor-positive/HER2-negative breast cancers. Breast Cancer Res Treat. 2018;168(1):135-45.
Tramm T, Di Caterino T, Jylling AM, Lelkaitis G, Lænkholm AV, Ragó P, et al. Standardized assessment of tumor-infiltrating lymphocytes in breast cancer: an evaluation of inter-observer agreement between pathologists. Acta Oncologica. 2018;57(1):90-4.
Cabuk FK, Aktepe F, Kapucuoglu FN, Coban I, Sarsenov D, Ozmen V. Interobserver reproducibility of tumor-infiltrating lymphocyte evaluations in breast cancer. Indian J Pathol Microbiol. 2018;61(2):181.
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