title: Sequential molecular analysis of circulating MCAM/MUC18 expression: a promising disease biomarker related to clinical outcome in melanoma.
abstract: MCAM/MUC18 is a cell adhesion molecule associated with higher incidence of relapse in melanoma. The purpose of our study was to evaluate its role as a promising disease biomarker of progression through sequential molecular MCAM/MUC18 RT-PCR assay on serial blood samples collected during the clinical follow-up of 175 melanoma patients in different American Joint Committee on Cancer (AJCC) stages. MCAM/MUC18 molecular detection, found at least once in 22 out of the 175 patients, was significantly associated with poor prognosis and death (p < 0.001), regardless of the AJCC stages. Positive expression, either if primarily present or later acquired, was associated with melanoma progression, whereas patients primarily negative or with subsequent loss gained clinical remission or stable disease, even if in advanced stages (p < 0.005). Six AJCC advanced stages always MCAM/MUC18 negative are in complete remission or with a stable disease (p < 0.007). Semiquantitative immunohistochemical MCAM/MUC18 staining on corresponding primary melanomas was related to peripheral molecular expression. Correlations between circulating molecular and tissutal immunohistochemical detection, primary tumour thickness, AJCC stages and clinical outcome were statistically evaluated using Student's t test, ANOVA, Spearman's rank correlation test, Pearson χ (2)-test and McNemar's test. In our investigation, MCAM/MUC18 expression behaves as a "molecular warning of progression" even in early AJCC patients otherwise in disease-free conditions. Achievement of this molecule predicted the emergence of a clinically apparent status, whereas absence or persistent loss was related to a stable disease or to a disease-free status. If confirmed in larger case series, MCAM/MUC18 molecular expression could predict good or poor clinical outcome, possibly becoming a promising prognostic factor.
authors.affiliation: Department of Laboratory Medicine, University of "Tor Vergata" Rome, Rome, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Rapanotti
authors.forename: Tara Mayte
authors.initials: TM
authors.lastname: Suarez Viguria
authors.forename: Gaetana
authors.initials: G
authors.lastname: Costanza
authors.forename: Ilaria
authors.initials: I
authors.lastname: Ricozzi
authors.forename: Andrea
authors.initials: A
authors.lastname: Pierantozzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Di Stefani
authors.forename: Elena
authors.initials: E
authors.lastname: Campione
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.forename: Sergio
authors.initials: S
authors.lastname: Chimenti
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.forename: Luca
authors.initials: L
authors.lastname: Bianchi
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D051929:CD146 Antigen / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis* / Q000401:mortality; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012074:Remission Induction; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000401:mortality; D016019:Survival Analysis; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D051929:CD146 Antigen; C497902:MCAM protein, human