Deciphering the association of spatial landscapes of DCIS with recurrence as invasive breast cancer

Ductal carcinoma in situ (DCIS) poses a risk of progression to invasive breast cancer (IBC). Researchers have identified a potential biomarker in the composition of stromal cells within DCIS, yet the relationship between the tumor microenvironment and recurrence remains unclear. In this study, spatial transcriptomic analyses were conducted on 49 primary DCIS specimens from patients who experienced no recurrence, DCIS recurrence, or recurrence as IBC.

The analysis revealed spatially organized gradients of stromal cells within DCIS, with increased presence of TREM2+ macrophages and myofibroblastic cancer-associated fibroblasts (myCAFs) in the proximity of the tumor. Specifically, the abundance of TREM2+ macrophages near tumor nests was found to be associated with a higher likelihood of subsequent recurrence as IBC.

Furthermore, the study identified specific ligand-receptor pair interactions, such as GRN--SORT1, SPP1--CD44, and LGALS9--CD44, between TREM2+ macrophages and epithelial cells, suggesting potential signaling mechanisms. To confirm these findings, multiplex immunostaining of serial sections was performed, validating these spatial relationships at the protein level.

This comprehensive characterization of the DCIS tumor microenvironment offers valuable insights into the factors contributing to disease progression, paving the way for the development of biomarkers to predict recurrence and the identification of potential therapeutic targets.