title: Tyrosinase messenger RNA in peripheral blood is related to poor survival in patients with metastatic melanoma following interleukin-2-based immunotherapy.
abstract: This study was conducted to examine the prognostic impact of four biomarkers [tyrosinase and MART-1 messenger RNA (mRNA), S100beta protein and lactate dehydrogenase (LDH)] in patients with metastatic melanoma, together with established clinical factors. Tyrosinase and MART-1 mRNA were measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). S100beta was measured using a commercially available immunoassay, and LDH was analysed conventionally. All markers were measured in blood samples before interleukin-2-based immunotherapy in 85 patients with metastatic melanoma. LDH, S100beta, tyrosinase, number of metastatic sites, location of metastatic sites and performance status were all significant factors for survival in univariate analyses. In multivariate analysis, tyrosinase [hazard ratio (HR)=1.6; 95% confidence interval (CI), 1.1-2.6; P=0.04] and LDH (HR=2.0; 95% CI, 1.1-3.5; P=0.02) were both independent prognostic factors for survival. A combination variable of tyrosinase and LDH remained independently associated with survival (P=0.04) after adjusting for the American Joint Committee on Cancer (AJCC) stage IV classification in a multivariate analysis involving both models. It can be concluded that tyrosinase mRNA and elevated LDH are independent prognostic factors for poor survival in this group of 85 patients. Additional studies are needed before the prognostic value of tyrosinase mRNA in metastatic melanoma can be firmly established. Further evaluation of the combined measurement of tyrosinase mRNA and LDH is warranted.
authors.affiliation: Department of Oncology bClinical Biochemistry, NBG, Aarhus University Hospital, Aarhus, Denmark. hesch@as.aaa.dk
authors.forename: Henrik
authors.initials: H
authors.lastname: Schmidt
authors.forename: Boe S
authors.initials: BS
authors.lastname: Sorensen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Fode
authors.forename: Ebba
authors.initials: E
authors.lastname: Nexo
authors.forename: Hans
authors.initials: H
authors.lastname: von der Maase
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007376:Interleukin-2 / Q000627:therapeutic use*; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D058965:MART-1 Antigen; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000096:biosynthesis / Q000235:genetics*; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood*; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D007376:Interleukin-2; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D007770:L-Lactate Dehydrogenase; D014442:Monophenol Monooxygenase