Reassessing Breast Cancer-Associated Fibroblasts (CAFs) Interactions with Other Stromal Components and Clinico-Pathologic Parameters by Using Immunohistochemistry and Digital Image Analysis (DIA)

Background: Breast cancer (BC) stroma has CD34- and αSMA-positive cancer-associated fibroblasts (CAFs) differently distributed. During malignant transformation, CD34-positive decrease while CAFs increase. The prevalence of in BC makes microscopic examination difficult without digital image analysis processing (DIA). DIA was used to compare among breast molecular subgroups. DIA-derived data were linked age, survival, tumor vessels, tertiary lymphoid structures (TLS), invasion, recurrence. Methods: Double immunostaining for CD34 αSMA showed different CAF distribution patterns normal tissues. Single immunohistochemistry on supplemental slides quantified CD34_CAFs. Digital (DIA) density, intensity, stromal score, H-score correlated with clinico-pathologic factors. Results: CD34/αSMA proportion significantly related age Luminal A (LA), B (LB), HER2 subtypes. CD34_CAF influence recurrence LA, LB-HER2, TNBC subtypes found be significant. CD34/αSMA-expressing exhibited a heterogeneous impact vasculature TLS. Conclusion: CD34_CAFs/αSMA_CAFs have an between assessment may predictive potential prognosis long-term follow-up patients cancer.