Exploration of Cancer Associated Fibroblasts Phenotypes in the Tumor Microenvironment of Classical and Pleomorphic Invasive Lobular Carcinoma

Authors

Harsh Batra
Qingqing Ding
Renganayaki Pandurengan
Heladio Ibarguen
Neus Bota Rabassedas
Aysegul Sahin
Ignacio Wistuba
Edwin Roger Parra
Maria Gabriela Raso

Publication Date

1-1-2023

Journal

Frontiers in Oncology

Abstract

UNLABELLED: As the second most common subtype of breast carcinoma, Invasive Lobular Carcinoma (ILC) microenvironment features have not been thoroughly explored. ILC has different histological subtypes and elucidating differences in their microenvironments could lead to a comprehensive development of cancer therapies. We designed a custom-made cancer associated fibroblast (CAFs) panel and used multiplex immunofluorescence to identify the differences in tumor microenvironment between Classic ILC and Pleomorphic ILC.

MATERIALS AND METHODS: Multiplex immunofluorescence were performed on formalin fixed paraffin embedded tissues using Opal-7 color kit. The antibodies used for phenotyping CAFs were Pan CK (AE1/AE3), CD45, A-SMA, FAP, S100, Thy-1 with optimized dilutions. The images were acquired and analyzed using Vectra 3.0 imaging system and InForm software respectively.

RESULTS: We studied 19 different CAFs colocalized phenotypes in the tumor, stroma and overall tissue compartments between classic and pleomorphic ILC. Total A-SMA+, A-SMA+FAP+S100+ and A-SMA+S100+ CAFs demonstrated higher densities in classic ILC cases while FAP+S100+ and S-100+ CAFs were increased in the pleomorphic subtype samples.

CONCLUSION: Our study explores multiple CAFs phenotypes between classical and pleomorphic ILC. We showed that CAFs subset differ between Classic ILC and Pleomorphic ILC. A-SMA CAFs are more prevalent in the TME of classic ILCs whereas Pleomorphic ILCs are dominated by CAFs without A-SMA expression. This also iterates the importance of exploring this particular type of breast carcinoma in more detail, paving the way for meaningful translational research.

DOI

10.3389/fonc.2023.1281650

PMID

38192631

PMCID

PMC10772146

PubMedCentral® Posted Date

12-21-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes