ABSTRACT
Simple, noninvasive methods are needed to follow effectiveness of new treatments in patients with melanoma. In our study, we examined cytoplasmic melanoma-associated antigen (CYT-MAA) serum level in melanoma patients during immunotherapy. Sera of 117 patients were assayed for CYT-MAA by double-sandwich ELISA before and during treatment with a polyvalent, shed antigen, melanoma vaccine. Vaccine-treated patients included 30 with American Joint Committee on Cancer (AJCC) stage IIb or IIIa, 30 with stage IIc, IIIb or IIIc, 30 with resected stage IV and 27 with measurable stage IV disease. Prior to vaccine therapy, 63% of patients had elevated serum CYT-MAA with high levels of antigen in all disease stages. After initiation of therapy, the level declined in more than 90% of the positive patients and fell below the positive cut-off in 56% of these patients within 5 months. By contrast, there was no decline in CYT-MAA serum level in 11 patients who served as untreated controls with melanoma. Multivariate analysis of the treated patients using accelerated failure time Weibull models adjusted for stage and age showed that patients whose CYT-MAA serum level remained elevated during treatment were approximately 3 times more likely to recur or progress than patients who were consistently below the positive cut-off (hazard ratio = 3.42, 95% CI [1.38, 8.47], p = 0.0079). Measurement of CYT-MAA serum level appears to show potential as an early marker of prognosis in patients with stages IIb to IV melanoma. Measurement of CYT-MAA serum level during therapy could provide an intermediate marker of response in these patients.
Subject(s)
Antigens, Neoplasm/blood , Biomarkers, Tumor/blood , Cancer Vaccines/therapeutic use , Melanoma/immunology , Skin Neoplasms/immunology , Adolescent , Adult , Aged , Cytoplasm , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Melanoma/drug therapy , Melanoma/pathology , Melanoma/surgery , Middle Aged , Multivariate Analysis , Neoplasm Staging , Odds Ratio , Predictive Value of Tests , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Skin Neoplasms/surgeryABSTRACT
With the goal of finding serological markers to monitor patients with early- as well as late-stage melanoma, we compared the levels of the cytoplasmic melanoma-associated antigens (CYT-MAA) and high-molecular-weight melanoma-associated antigen (HMW-MAA) in the sera of melanoma patients and controls. Using double-sandwich ELISA, we measured levels of both antigens in 117 patients and in 62 age- and sex-matched controls. Patients were stratified into four risk group based on stage of the disease. Serum levels of both markers were significantly higher in melanoma patients than in controls. CYT-MAA was the more sensitive marker, with 61% of patients showing elevated levels regardless of the stage of disease. HMW-MAA was elevated in 29%. Elevated CYT-MAA was also significantly correlated with poorer clinical outcome. By multivariate analysis (adjusting for stage and age), patients who had elevated CYT-MAA were 81% more likely to recur than patients with undetectable levels (hazard ratio=1.81, 95% CI=[1.07, 3.06], p-value=0.03). Elevated levels of HMW-MAA did not correlate with poor prognosis. These results suggest that both CYT-MAA and HMW-MAA are serum markers for residual melanoma in patients with resected disease. Furthermore, CYT-MAA appears to be a prognostic marker of clinical outcome in melanoma vaccine-treated patients.
