Lymphatic expression of the proliferation marker Ki67 is linked to sentinel node positivity, recurrence and mortality in primary cutaneous melanoma

Abstract

Lymphangiogenesis is a precursor to lymphovascular invasion, and may therefore signal a higher risk of metastasis and mortality in primary cutaneous melanoma. This retrospective longitudinal study aimed to evaluate whether emergent lymphangiogenesis, as measured through co‐expression of endothelial proteins with the proliferation marker Ki67, was associated with poorer prognosis in a cohort of patients with single primary cutaneous melanoma. We screened all patients with a single locally invasive primary cutaneous melanoma who received sentinel lymph node biopsy at a tertiary dermatology centre in Brisbane, Australia between 1994 and 2007. Primary melanoma sections were stained via Opal multiplex immunofluorescence, and categorized according to the presence of Ki67 within either CD31+ or D2‐40+ endothelial cells. Multivariate Cox regression modelling was used to evaluate associations between endothelial Ki67 positivity and clinical outcomes, with adjustment for age, sex, Breslow depth, ulceration, and anatomical location. Overall, 264 patients were available for analysis, with a median follow‐up duration of 7.1 years. The presence of D2‐40+/Ki67+ co‐expression was associated with greater melanoma‐specific mortality (adjusted hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.33–3.10; p = 0.001) and recurrence (adjusted HR: 1.70; 95% CI: 1.33–3.10; p = 0.001) relative to absence. CD31+/Ki67+ co‐expression was not prognostic in this cohort. Lymphatic proliferation, as measured through D2‐40+/Ki67+ co‐expression, predicted greater melanoma‐specific mortality and recurrence in this cohort of primary cutaneous melanoma.