title: Circulating melanoma cells as a potential biomarker to detect metastasis and evaluate prognosis.
abstract: TNM staging is mainly used to evaluate the prognosis of melanoma patients. Serum biomarkers such as 5-S-cysteinyldopa (5-S-CD) have occasionally been used but most do not respond until the tumour burden becomes high. Recently, circulating melanoma cells (CMC) have been reported as a possible new biomarker to detect metastasis, monitor treatment response and predict prognosis. The object of this exploratory study was to evaluate the efficacy of CMC to detect metastasis and predict prognosis by cross-sectional and prospective observational analyses, respectively. Altogether 15 patients with stages II-IV melanoma were enrolled and CMC were enumerated by CellSearch system with cut-off values of two cells/7.5 mL. Serum 5-S-CD and lactate dehydrogenase (LDH) were also measured. The sensitivity of CMC and 5-S-CD for the detection of metastasis was 33 and 50%, respectively. The combination of CMC and 5-S-CD showed a sensitivity of 67%, the best performance among CMC, 5-S-CD, LDH and any combination of two of the markers. Additionally, a 30-month prospective observation showed that CMC could segregate patients with poorer prognosis. The median survival time for the patients with <2 CMC and those with ≥2 CMC was 19.5 and 4.5 months, respectively. The limitation of this study is the small sample size. These preliminary results indicate CMC may complement the efficacy of 5-S-CD to detect metastasis and can be a prognostic marker. Although there is still room for improvement to maximise the sensitivity, the CellSearch system is reproducible, standardised and suitable for multi-centre studies.
authors.affiliation: Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tokimasa
authors.initials: T
authors.lastname: Hida
authors.affiliation: Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yoneta
authors.affiliation: Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.affiliation: Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yanagisawa
authors.affiliation: Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yasue
authors.initials: Y
authors.lastname: Ishii-Osai
authors.affiliation: Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kan
authors.affiliation: Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
authors.affiliation: Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D003430:Cross-Sectional Studies; D003548:Cysteinyldopa / Q000097:blood; D005260:Female; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D008545:Melanoma / Q000097:blood* / Q000175:diagnosis* / Q000556:secondary; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D003548:Cysteinyldopa; D007770:L-Lactate Dehydrogenase
keywords: 5-S-cysteinyldopa; CD146; circulating tumour cells; high molecular weight melanoma-associated antigen; malignant melanoma