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ABSTRACT: Introduction:Although sentinel lymph node (SLN) status is the most powerful predictor of prognosis in patients with clinically localized melanoma, a proportion of melanoma patients with histologically negative SLNs will still recur. It is hypothesized that tumor response may be altered or mediated by specific cytokines. We therefore investigated whether levels of IL-4, IL-6, IL-10, TNF-, or IFN- would predict disease recurrence in melanoma patients with histologically negative SLNs.Methods:This prospective cohort study involved 218 patients with clinically localized melanoma who underwent a histologically negative SLN biopsy. Preoperative plasma cytokine levels were determined by enzyme-linked immunosorbent assay on these patients, as well as on 90 healthy controls. Kaplan-Meier life tables were constructed, and Cox proportional hazards analyses were performed to assess predictors of disease-free survival (DFS).Results:At a median follow-up of 43 months, 33 of 218 patients (15%) had suffered disease recurrence. Melanoma patients had significant elevations of IL-4, IL-6, and IL-10 compared to healthy controls; levels of IFN- were less elevated in melanoma patients compared to controls. Despite this, melanoma patients with detectable IFN- levels were at significantly higher risk for recurrence compared to patients with undetectable levels (5-year DFS 70% vs. 86%, P = .03). On multivariate analysis including standard melanoma prognostic factors, only tumor thickness (P = .004) and the presence of detectable IFN- levels (P = .05) were significant independent prognostic factors for disease-free survival.Conclusions:Among melanoma patients with clinically localized disease who have undergone a histologically negative SLN biopsy, presence of a detectable plasma level of IFN- is an independent predictor of disease recurrence. Elevated levels of IFN- may identify a group of early-stage melanoma patients who are more likely to have recurrence of disease and who may benefit from adjuvant therapies, including immunotherapies.
Annals of Surgical Oncology 04/2012; 8(2):116-122. · 4.17 Impact Factor
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ABSTRACT: BackgroundIncreased interferon γ (IFN-γ) levels are an independent predictor of melanoma recurrence. Human leukocyte antigen (HLA) class
II genes can regulate cytokine production; we investigated whether these genes would predict IFN-γ levels and recurrence in
melanoma patients.
MethodsOf 591 patients who presented with localized melanoma, 579 underwent identification of HLA class II alleles; 233 melanoma
patients and 90 controls underwent determination of plasma IFN-γ levels. HLA class II genes were examined for association
with IFN-γ levels and disease recurrence.
ResultsAfter a median follow-up of 60 months, melanoma patients with IFN-γ levels above the mean control value were more likely to
have developed disease recurrence compared with patients with levels below the mean. The HLA class II geneHLA-DRB1*1101 was the strongest predictor of recurrence, andHLA-DRB1*1101-positive melanoma patients had increased levels of IFN-γ compared with patients lacking the gene.
ConclusionsAmong patients with localized melanoma, bothHLA-DRB1*1101 and increased IFN-γ levels were associated with an increased risk for recurrence;HLA-DRB1*1101-positive patients had relatively increased levels of IFN-γ. HLA class II genes may mediate cytokine production in melanoma
patients, and this mechanism may help determine the risk of disease recurrence.
Annals of Surgical Oncology 04/2012; 9(6):587-593. · 4.17 Impact Factor
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ABSTRACT: Increased interferon gamma (IFN-gamma) levels are an independent predictor of melanoma recurrence. Human leukocyte antigen (HLA) class II genes can regulate cytokine production; we investigated whether these genes would predict IFN-gamma levels and recurrence in melanoma patients.
Of 591 patients who presented with localized melanoma, 579 underwent identification of HLA class II alleles; 233 melanoma patients and 90 controls underwent determination of plasma IFN-gamma levels. HLA class II genes were examined for association with IFN-gamma levels and disease recurrence.
After a median follow-up of 60 months, melanoma patients with IFN-gamma levels above the mean control value were more likely to have developed disease recurrence compared with patients with levels below the mean. The HLA class II gene HLA-DRB1*1101 was the strongest predictor of recurrence, and HLA-DRB1*1101-positive melanoma patients had increased levels of IFN-gamma compared with patients lacking the gene.
Among patients with localized melanoma, both HLA-DRB1*1101 and increased IFN-gamma levels were associated with an increased risk for recurrence; HLA-DRB1*1101-positive patients had relatively increased levels of IFN-gamma. HLA class II genes may mediate cytokine production in melanoma patients, and this mechanism may help determine the risk of disease recurrence.
Annals of Surgical Oncology 08/2002; 9(6):587-93. · 4.17 Impact Factor
