Researchers exploring prognostic biomarkers in primary cutaneous melanoma have identified peritumoral lymphatic vessel density, lymphatic invasion, and proliferating lymphatic endothelium as key indicators for patient prognosis. Published in PubMed, the systematic review analyzed multiple studies to determine which vascular metrics add critical prognostic value beyond conventional histopathology.
Cutaneous melanoma spreads preferentially through the lymphatic system, making sentinel lymph node status one of the strongest prognostic factors for patients. To determine whether tumor angiogenesis and lymphangiogenesis can improve risk stratification, researchers conducted a systematic review searched to Sept. 10, 2026, according to PubMed. The review examined blood microvascular density, intratumoral and peritumoral lymphatic vessel density, Ki-67-positive proliferating lymphatic vessels, and lymphatic invasion.
Peritumoral Vessel Density and Metastasis Risk
The systematic review evaluated data from a reference meta-analysis by Pastushenko et al. from 2014 alongside newer cutaneous study units and ocular studies. While earlier findings showed that peritumoral lymphatic vessel density and lymphatic invasion were associated with metastasis—while blood microvascular density and intratumoral density were not—newer cohorts provided precise adjusted effect sizes. According to PubMed, peritumoral lymphatic vessel density predicted disease-free survival with a hazard ratio of 2.14 and melanoma-specific survival with a hazard ratio of 2.74, with a 95% confidence interval ranging from 1.31 to 5.73.
Additionally, immunohistochemically detected lymphatic invasion successfully predicted sentinel node metastasis, with affected cases showing 33% positive nodes compared to 11% in negative cases, while also forecasting overall survival. In a cohort of 264 patients, a Ki-67-positive lymphatic endothelium predicted melanoma-specific mortality with an adjusted hazard ratio of 2.03 and a 95% confidence interval from 1.33 to 3.10. Meanwhile, blood microvascular density and blood endothelial proliferation showed no prognostic value.
Endothelial ICAM-1 and T-Cell Exclusion
A separate study published on PubMed examined how vascular mechanisms regulate T-cell positioning within the tumor microenvironment. Using RNA sequencing of endothelial cells from tumor cores versus peripheries in a mouse melanoma model, researchers identified intercellular adhesion molecule-1 as a candidate regulator of T-cell localization. During tumor growth, T cells shifted from a balanced core-margin distribution to marked exclusion from the core, particularly in T cell-inflamed tumors.
This spatial polarization coincided with high expression of lymphocyte function-associated antigen-1 on T cells. Endothelial intercellular adhesion molecule-1 became enriched at the tumor periphery, where vascular integrity was compromised due to increased vascular leakage and reduced pericyte coverage. Blocking intercellular adhesion molecule-1 restored T-cell infiltration, enhanced effector activity, delayed the growth of immunogenic tumors, and sensitized an immune-refractory tumor to anti-programmed cell death protein 1 blockade, according to the PubMed study.