Significance of plasma cytokine levels in melanoma patients with histologically negative sentinel lymph nodes

Introduction: Although sentinel lymph node (SLN) status is the most powerfu l predictor of prognosis in patients with clinically localized melanoma, a proportion of melanoma patients with histologically negative SLNs will stil l recur. It is hypothesized that turner response may be altered or mediated by specific cytokines. We therefore investigated whether levels of IL-4, I L-6, IL-10, TNF-alpha, or IFN-gamma would predict disease recurrence in mel anoma patients with histologically negative SLNs. Methods: This prospective cohort study involved 218 patients with clinicall y localized melanoma who underwent a histologically negative SLN biopsy. Pr eoperative plasma cytokine levels were determined by enzyme-linked immunoso rbent assay on these patients, as well as on 90 healthy controls. Kaplan-Me ier life tables were constructed, and Cox proportional hazards analyses wer e performed to assess predictors of disease-free survival (DFS). Results: At a median follow-up of 43 months, 33 of 218 patients (15%) had s uffered disease recurrence. Melanoma patients had significant elevations of IL-4, IL-G, and IL-10 compared to healthy controls; levels of IFN-gamma we re less elevated in melanoma patients compared to controls. Despite this, m elanoma patients with detectable IFN-gamma levels were at significantly hig her risk for recurrence compared to patients with undetectable levels (5-ye ar DFS 70% vs. 86%, P = .03). On multivariate analysis including standard m elanoma prognostic factors, only tumor thickness (P = .004) and the presenc e of detectable IFN-gamma levels (P = .05) were significant independent pro gnostic factors for disease-free survival. Conclusions: Among melanoma patients with clinically localized disease who have undergone a histologically negative SLN biopsy, presence of a detectab le plasma level of IFN-gamma is an independent predictor of disease recurre nce. Elevated levels of IFN-gamma may identify a group of early-stage melan oma patients who are more likely to have recurrence of disease and who may benefit from adjuvant therapies, including immunotherapies.