MACROPHAGES AND SURVIVAL IN STAGES I/II MELANOMA

Macrophage Markers in Serum and Tumor Have Prognostic Impact in American Joint Committee on Cancer Stage I/II Melanoma

Trine O. Jensen, Henrik Schmidt, Holger Jon Møller, Morten Høyer, Maciej Bogdan Maniecki, Pia Sjoegren, Ib Jarle Christensen, Torben Steiniche

From the Cancer Immunotherapy Group and Departments of Oncology, Clinical Biochemistry, and Plastic Surgery, Aarhus University Hospital, Aarhus; the Finsen Laboratory, Rigshospitalet, Copenhagen; and Department of Pathology, Vejle Hospital, Vejle, Denmark.

Corresponding author: Trine O. Jensen, MD, Department of Oncology, Aarhus University Hospital, Norrebrogade 44, 8000 Aarhus C, Denmark; e-mail: trinejen@rm.dk.

Purpose To evaluate the prognostic role of soluble CD163 (sCD163) in serum and macrophage infiltration in primary melanomas from patients with American Joint Committee on Cancer (AJCC) stage I/II melanoma. The scavenger receptor CD163 is associated with anti-inflammatory macrophages, and it is shed from their surface.

Patients and Methods Serum samples from 227 patients with stage I/II melanoma obtained before definitive surgery (baseline) and during 5 years of follow-up were analyzed for sCD163 by enzyme-linked immunosorbent assay. Excised formalin-fixed, paraffin-embedded primary melanomas from 190 patients were available for immunohistochemical analyzes of CD163⁺ and CD68⁺ macrophage infiltration. They were estimated semiquantitatively in three different tumor compartments: tumor nests, tumor stroma, and at the invasive front of the tumor.

Results Serum sCD163 treated as an updated continuous covariate as well as the baseline value were analyzed together with the covariate's ulceration and thickness in a Cox proportional hazards model. sCD163 was an independent prognostic factor for overall survival (baseline, hazard ratio [HR] = 1.4; 95% CI, 1.1 to 1.7; P = .01; and updated, HR = 1.4; 95% CI, 1.1 to 1.8; P = .003). Melanomas with dense CD163⁺ macrophage infiltration in tumor stroma and CD68⁺ macrophage infiltration at the invasive front were associated with poor overall survival (CD163, HR = 2.7; 95% CI, 0.8 to 9.3; P = .11; and CD68, HR = 2.8; 95% CI, 1.2 to 6.8; P = .02) independent (borderline for CD163) of thickness and ulceration.

Conclusion Both serum levels of sCD163 and the presence of CD68⁺ macrophage infiltration at the tumor invasive front are independent predictors of survival in AJCC stage I/II melanoma. CD163⁺ cell infiltration in tumor stroma may be predictive of survival.