Relationship between vascular density and microenvironment in medullary thyroid carcinoma

This study explored the interplay between vascular density and the immune microenvironment in medullary thyroid carcinoma (MTC) to elucidate their impact on tumor behavior. Using tissue microarray (TMA) analysis of 24 histopathologically confirmed MTC cases, we assessed immune cell infiltration (CD68+ macrophages, CD3+/CD4+/CD8+/CD20+ lymphocytes, granzyme B, and FOXP3+) and vascular markers (D2-40, CD31, and ERG) across tumor regions: center, interface, adjacent normal tissue, and metastases. Vascular density was quantified using ImageJ, while immune markers were analyzed using the QuPath software. The key findings revealed distinct spatial heterogeneity in the vascular distribution. D2-40+ lymphatic vessel density was significantly elevated in adjacent normal tissue compared to the tumor center (P < 0.05), whereas ERG+ microvessel density was the highest at the tumor interface. ERG+ vascular density at the interface was positively correlated with mast cell infiltration (Spearman = 0.571, P = 0.009). D2-40+ density in the tumor center was associated with CD8+ T-cell infiltration (Spearman = 0.488, P = 0.025), while interface D2-40+ density was correlated with CD3+ (Spearman = 0.584, P = 0.009), CD8+ (Spearman = 0.508, P = 0.022), and granzyme B+ cells (Spearman = 0.482, P = 0.031). CD31+ vascular density in adjacent normal tissues showed a positive relationship with FOXP3+ regulatory T cells (Tregs) (Spearman = 0.456, P = 0.05). Patients with distant metastases exhibited a higher D2-40+ density in tumor centers than non-metastatic cases (P = 0.024). These results underscore the dynamic relationship between vascular architecture and immune infiltration in MTC, highlighting region-specific interactions that may influence tumor progression. The elevated D2-40+ density in metastatic cases and distinct immunovascular correlations suggest potential prognostic markers and therapeutic targets.