Work

Stromal VEGF-C expression predicts nodal metastasis: implications for axillary surgery de-escalation in breast cancer

Year: 2026

Type: article

Abstract: Accurate preoperative prediction of lymph node metastasis (LNM) could facilitate more individualized axillary management in breast cancer by improving identification of patients at lower risk of nodal involvement while maintaining appropriate staging for those at higher risk. Yet, reliable molecular predictors of LNM remain lacking. VEGF-C, a key driver of lymphangiogenesis, is expressed in both cancer cell and stromal compartments, but its clinical utility is unclear. In a prospectively enrolled cohort, we assessed stromal and cancer cell VEGF-C expression by immunohistochemistry using both manual scoring and a novel automated image analysis script enabling objective, reproducible classification of stromal versus epithelial cells at scale. Stromal VEGF-C was independently associated with LNM after adjustment for established predictors (P = 0.004), with prediction models reaching AUCs of up to 0.784. Cancer cell VEGF-C added no predictive value. In exploratory analyses, stromal VEGF-C provided predictive information comparable to that of vascular invasion, a strong predictor of LNM that is generally unavailable preoperatively. These findings identify stromal VEGF-C as a potential preoperative biomarker for nodal risk stratification. However, given the observational and predictive nature of the present study, stromal VEGF-C should be considered complementary to, rather than a replacement for, established pathological predictors. Its potential contribution to future axillary surgery de-escalation strategies warrants prospective validation.

Source: npj Precision Oncology

DOI: 10.1038/s41698-026-01770-x