title: Prognostic significance of peripheral blood and bone marrow tyrosinase messenger RNA in malignant melanoma.
abstract: The objectives of this study were to evaluate the prognostic significance of reverse transcription PCR (RT-PCR) detection of tyrosinase mRNA in the peripheral blood (PB) and bone marrow (BM) of patients with stage II-IV malignant melanoma (MM). Seventy-three PB samples and 109 BM aspirates from 123 assessable patients with stage II-IV MM were analyzed for tyrosinase mRNA using nested RT-PCR. Twenty-five controls without MM were also evaluated. The RT-PCR results were correlated with overall survival (OS) and clinical stage. Overall, 23 of the 123 patients with MM (19%) had tyrosinase mRNA in their blood and/or BM. RT-PCR positivity 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 tyrosinase PCR negative. There was no correlation between RT-PCR results and clinical stage. Within stage II, BM PCR-positive patients had a shorter median survival (24 months) than BM PCR-negative individuals (median not reached), with a P approaching significance (P = 0.06). There was a statistically significant correlation between blood PCR positivity and decreased overall survival (P = 0.03) in all patients. Blood PCR 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 tyrosinase 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 predictor 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.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Ghossein
authors.forename: D
authors.initials: D
authors.lastname: Coit
authors.forename: M
authors.initials: M
authors.lastname: Brennan
authors.forename: Z F
authors.initials: ZF
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: A
authors.initials: A
authors.lastname: Houghton
authors.forename: J
authors.initials: J
authors.lastname: Rosai
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001853:Bone Marrow / Q000201:enzymology*; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000201:enzymology* / Q000556:secondary; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000096:biosynthesis*; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D014442:Monophenol Monooxygenase