António Polónia1,2,3,4, Regina Pinto1,2,3, Jorge F Cameselle-Teijeiro5, Fernando C Schmitt1,2,3,4,6, Joana Paredes1,2,4. 1. Epithelial Interactions in Cancer (EPIC), i3S-Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal. 2. Ipatimup, Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal. 3. Department of Pathology, Ipatimup Diagnostics, Ipatimup, University of Porto, Porto, Portugal. 4. FMUP, Faculty of Medicine, University of Porto, Porto, Portugal. 5. Complexo Hospitalar Universitario de Vigo (CHUVI), Vigo, Spain. 6. Laboratoire National de Santé, Dudelange, Luxembourg.
Abstract
AIM: The present work aims to evaluate the presence of stromal tumour-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PDL1) expression in breast carcinomas and their correlation with available clinicopathological features. METHODS: Two independent series of invasive breast cancer (IBC), one including ductal carcinoma in situ (DCIS) pair-matched cases, were selected, and quantification of TILs was accomplished in each case. Immunohistochemistry was also performed to evaluate the expression of PDL1. RESULTS: In both cohorts evaluated, increased stromal TILs and PDL1 expression were present in about 10% of IBCs, being significantly associated with each other and both with grade 3 and triple-negative subtype. We observed a similar distribution of stromal TILs and PDL1 expression between DCIS and IBC. Finally, we observed that increased stromal TILs and PDL1 expression were significantly associated with cancer stem cell (CSC) markers, basal cell markers and vimentin expression. Interestingly, in IBC cases with vimentin expression, increased stromal TILs, as well as decreased PDL1 expression, disclosed a better clinical outcome, independently of the main classical BC prognostic factors. CONCLUSIONS: We have confirmed the association of stromal TILs and PDL1 expression with aggressive forms of BC and that both are already found in in situ stages. We also showed that stromal TILs and PDL1 expression are associated with clinical outcome in cases enriched for a mesenchymal immunophenotype. We describe for the first time a close relationship between CSC markers and PDL1 expression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
AIM: The present work aims to evaluate the presence of stromal tumour-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PDL1) expression in breast carcinomas and their correlation with available clinicopathological features. METHODS: Two independent series of invasive breast cancer (IBC), one including ductal carcinoma in situ (DCIS) pair-matched cases, were selected, and quantification of TILs was accomplished in each case. Immunohistochemistry was also performed to evaluate the expression of PDL1. RESULTS: In both cohorts evaluated, increased stromal TILs and PDL1 expression were present in about 10% of IBCs, being significantly associated with each other and both with grade 3 and triple-negative subtype. We observed a similar distribution of stromal TILs and PDL1 expression between DCIS and IBC. Finally, we observed that increased stromal TILs and PDL1 expression were significantly associated with cancer stem cell (CSC) markers, basal cell markers and vimentin expression. Interestingly, in IBC cases with vimentin expression, increased stromal TILs, as well as decreased PDL1 expression, disclosed a better clinical outcome, independently of the main classical BC prognostic factors. CONCLUSIONS: We have confirmed the association of stromal TILs and PDL1 expression with aggressive forms of BC and that both are already found in in situ stages. We also showed that stromal TILs and PDL1 expression are associated with clinical outcome in cases enriched for a mesenchymal immunophenotype. We describe for the first time a close relationship between CSC markers and PDL1 expression. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
Entities:
Keywords:
BREAST CANCER; CANCER STEM CELLS; TUMOUR IMMUNITY; TUMOUR MARKERS
Authors: Marcelo Sobral-Leite; Koen Van de Vijver; Magali Michaut; Rianne van der Linden; Gerrit K J Hooijer; Hugo M Horlings; Tesa M Severson; Anna Marie Mulligan; Nayana Weerasooriya; Joyce Sanders; Annuska M Glas; Diederik Wehkamp; Lorenza Mittempergher; Kelly Kersten; Ashley Cimino-Mathews; Dennis Peters; Erik Hooijberg; Annegien Broeks; Marc J van de Vijver; Rene Bernards; Irene L Andrulis; Marleen Kok; Karin E de Visser; Marjanka K Schmidt Journal: Oncoimmunology Date: 2018-09-11 Impact factor: 8.110