PROGNOSTIC-SIGNIFICANCE OF PERIPHERAL-BLOOD AND BONE-MARROW TYROSINASE MESSENGER-RNA IN MALIGNANT-MELANOMA

The objectives of this study were to evaluate the prognostic significa nce of reverse transcription PCR (RT-PCR) detection of tyrosinase mRNA in the peripheral blood (PB) and bone marrow (BM) of patients with st age II-IV malignant melanoma (MM), Seventy-three PB samples and 109 BM aspirates from 123 assessable patients with stage II-IV MM were analy zed for tyrosinase mRNA using nested RT-PCR, Twenty-five controls with out MM were also evaluated. The RT-PCR results were correlated with ov erall survival (OS) and clinical stage. Overall, 23 of the 123 patient s with MM (19%) had tyrosinase mRNA in their blood and/or BM, RT-PCR p ositivity was present in the PB of 9 of 73 patients (12%), whereas 18 of 109 (16.5%) had tyrosinase mRNA in their BM. All controls were tyro sinase PCR negative, There was no correlation between RT-PCR results a nd clinical stage, Within stage II, BM PCR-positive patients had a sho rter median survival (24 months) than BM PCR-negative individuals (med ian not reached), with a P approaching significance (P = 0.06), There was a statistically significant correlation between blood PCR positivi ty and decreased overall survival (P = 0.03) in all patients, Blood PC R positivity was associated with a significantly decreased OS in stage II and III (P = 0.01 and 0.02, respectively) and was not a predictor of OS in stage IV, In multivariate analysis, blood RT-PCR for tyrosina se mRNA was found to be an independent predictor of survival (P = 0.03 ; risk ratio, 2.87), RT-PCR can specifically detect tyrosinase mRNA in the PB and BM of patients with MM. Blood RT-PCR is an independent pre dictor of overall survival in stage II-III MM. Additional studies are needed to define the potential role of this assay in the management of patients with advanced melanoma.