Poster
Characterization of ER-positive Invasive breast carcinoma by spatial transcriptomics
Authors: Aljelaify, Rasha; Mikkola, Lea; Abalo, Xesus; Zerdes, Ioannis; Acs, Balazs; Sun, Wenwen; Lundeberg, Joakim; Abed AlThagafi, Malak; Daub, Carsten
Conference name: 9th ScanPath - the Scandinavian Symposium on Translational Pathology 2025
Publication year: 2025
Book title : 9th ScanPath Symposium Book of Abstracts
Background:
Intratumor heterogeneity is a hallmark of breast cancer. Estrogen receptor (ER)-positive invasive carcinoma, the most common breast cancer subtype, displays marked molecular and spatial variability across tumor and microenvironmental compartments.
Objective:
To map gene expression programs in ER-positive invasive carcinoma in relation to histology and assess tumor-microenvironment interactions.
Methods:
Spatial Transcriptomics (10x Genomics Visium) was applied to profile ER-positive invasive carcinoma tissue sections. Transcriptomic data were analyzed in relation to histopathological annotations, biomarkers, and molecular subtype classifiers.
Results:
We observed higher fractions of cycling cells in tumor regions and in stromal and fat compartments of tumor-bearing sections compared with controls, with the effect most consistent in stroma. Biomarker-level analysis confirmed concordance between ER and progesterone receptor (PR) expression and clinical pathology, while uncovering spatial heterogeneity in HER2 expression and enabling PAM50-based molecular subtyping. Global transcriptomic clustering recapitulated morphological compartments defined by pathology, while higher-resolution analysis revealed distinct tumor clusters, each with unique transcriptional programs. Pathway-level analysis delineated luminal, stromal, immune, and stress/interface states, refining the landscape of tumor–microenvironment interactions. Module scoring revealed heterogeneous immune contributions, with plasma cell programs detected in ~60% of tumor spots and macrophage-related programs present more focally (M1: ~29%, M2: ~5%, TAM_SPP1: ~18%).
Conclusions: Spatial transcriptomics provides a detailed characterization of ER-positive invasive carcinoma, linking histopathology with spatial gene expression programs. These findings highlight clinically relevant features, including widespread plasma cell enrichment and heterogeneous macrophage infiltration, with potential implications for prognosis and treatment stratification in breast cancer.
