The prognostic role of protumoral macrophages in AJCC stage I/II melanoma

Abstract

9017 Background: Depending on the micro-environmental signals in solid tumors, macrophages have pivotal functions: Anti- tumoral, killing tumor cells or pro-tumoral mediating tumor cell growth and invasion. The scavenger receptor CD163 is associated with pro-tumoral macrophages and it is shed from their surface (soluble CD163), in response to inflammatory stimuli. We studied CD163 expression in blood and primary melanomas from patients with stage I/II disease. Methods: 2,200 serum samples from 227 patients with stage I/II melanoma were collected during a 5-year follow-up period at the Plastic Surgery Department, Aarhus University Hospital in 1997 to 2002. In 190 of these patients paraffin embedded primary melanomas were available for examination.Tumor macrophage infiltration was studied by immunohistochemistry (anti-CD163) and estimated semi-quantitatively (5 categorical values) in three tumor compartments: tumor islets, stroma surrounding tumor islets, and at the invasive front of the tumor. Soluble CD163 in patients’ serum were analyzed with ELISA technique. The endpoints of this retrospective study were: Overall survival (OS) and progression-free survival (PS). Results: During a follow-up period of 61 months (range, 1 to 114 months), 44 relapses and 41 deaths were observed. CD163+ cell infiltration in stroma and tumor islets was analyzed with ulceration and thickness in a Multivariate Cox proportional hazard model. A high stromal infiltration of CD163+ macrophages was an independent prognostic factor of poor OS (hazard ratio [HR] = 3.7; 95% CI, 1.1–12.5; p=0.03) and of short PS ([HR] = 3.4; 95% CI, 1.0–11.5; p=0.05) together with thickness. Soluble CD163 treated as an updated continuous covariate as well as the baseline value was analyzed in a Cox proportional hazard model. There was no correlation to survival. Conclusions: High infiltration of CD163+ macrophages in stroma of primary melanoma was an independent prognostic factor of relapse and death in stage I/II melanoma. Results must be confirmed in an independent study. No significant financial relationships to disclose.