Characterisation of the Stromal Microenvironment in Lobular Breast Cancer

Laura Gomez Cuadrado, Esme Bullock, Zeanap Mabruk, Hong Zhao, Margarita Souleimanova , Pernille Rimmer Noer, Arran K Turnbull, Claus Oxvig, Nicholas Bertos, Adam Byron, MIchael Dixon, Morag Park, Syed Haider, Rachael Natrajan, Andrew H Sims, Valerie G Brunton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer, and it exhibits a number of clinico-pathological characteristics distinct from the more common invasive ductal carcinoma (IDC). We set out to identify alterations in the tumor microenvironment (TME) of ILC. We used laser-capture microdissection to separate tumor epithelium from stroma in 23 ER+ ILC primary tumors. Gene expression analysis identified 45 genes involved in regulation of the extracellular matrix (ECM) that were enriched in the non-immune stroma of ILC, but not in non-immune stroma from ER+ IDC or normal breast. Of these, 10 were expressed in cancer-associated fibroblasts (CAFs) and were increased in ILC compared to IDC in bulk gene expression datasets, with PAPPA and TIMP2 being associated with better survival in ILC but not IDC. PAPPA, a gene involved in IGF-1 signaling, was the most enriched in the stroma compared to the tumor epithelial compartment in ILC. Analysis of PAPPA- and IGF1-associated genes identified a paracrine signaling pathway, and active PAPP-A was shown to be secreted from primary CAFs. This is the first study to demonstrate molecular differences in the TME between ILC and IDC identifying differences in matrix organization and growth factor signaling pathways
Original languageEnglish
Early online date11 Feb 2022
Publication statusE-pub ahead of print - 11 Feb 2022

Keywords / Materials (for Non-textual outputs)

  • lobular breast cancer
  • tumor microenvironment;
  • cancer-associated fibroblasts


Dive into the research topics of 'Characterisation of the Stromal Microenvironment in Lobular Breast Cancer'. Together they form a unique fingerprint.

Cite this