Characterisation of the Stromal Microenvironment in Lobular Breast Cancer

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Invasive lobular carcinoma (ILC) is the second most common breast cancer subtype.
• ILC exhibits distinct clinico-pathological features compared to invasive ductal carcinoma (IDC).
• The tumor microenvironment (TME) plays a crucial role in cancer progression and treatment response.

Purpose of the Study:

• To identify molecular alterations in the TME specific to ILC.
• To compare the TME of ILC with that of IDC and normal breast tissue.
• To investigate the role of specific genes and signaling pathways in ILC TME.

Main Methods:

• Laser-capture microdissection to isolate tumor epithelium and stroma from 23 ER+ ILC primary tumors.
• Gene expression analysis to identify differentially expressed genes in the ILC TME.
• Bioinformatic analysis to explore extracellular matrix (ECM) regulation and growth factor signaling pathways.

Main Results:

• 45 ECM-related genes were enriched in the non-immune stroma of ILC compared to IDC and normal breast tissue.
• Ten of these genes, including PAPP-A and TIMP2, were expressed in cancer-associated fibroblasts (CAFs) and associated with better survival in ILC.
• PAPP-A, involved in IGF-1 signaling, was highly enriched in the ILC stroma and secreted by CAFs, suggesting a paracrine signaling pathway.

Conclusions:

• This study reveals significant molecular differences in the TME between ILC and IDC.
• Alterations in matrix organization and growth factor signaling pathways, particularly involving PAPP-A, characterize the ILC TME.
• These findings provide novel insights into ILC biology and potential therapeutic targets.