title: Assessment of melanoma-initiating cell markers and conventional parameters in sentinel lymph nodes of malignant melanoma.
abstract: Sentinel lymph node (SLN) biopsies have widely been used for the detection of occult LN metastasis of malignant melanoma (MM). In addition to conventional biomarkers, we assessed the diagnostic and prognostic significance of melanoma-initiating cell (MIC) markers in SLNs of MM. We examined the expressions of gp100, MART-1 and tyrosinase mRNA for routine diagnosis and those of ABCB5, CD133, nestin, KDM5B, NGFR and RANK mRNA as MIC markers. The presence of micrometastasis was confirmed immunohistochemically using antibodies to S-100, HMB-45, MART-1, and tyrosinase. Discordance between immunohistochemical and molecular data was observed in 14 of 70 (20.0%) patients, among whom five (7.1%) were positive for only molecular markers;two of these five patients tested positive for micrometastasis by repeated immunohistochemical stainings. The quantitative expression levels of gp100, MART-1, and tyrosinase mRNA were significantly higher in the metastatic LNs;the cut-off values remain to be elucidated. ABCB5 mRNA expression was detected more frequently in the metastatic SLNs (p＜0.05) and in the group of patients with recurrence. To make a definite diagnosis of metastasis, we still need a combination of immunohistochemical and molecular probes. ABCB5 might be a suitable molecular marker for the detection of melanoma-initiating cells in SLNs.
authors.affiliation: Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Suzuki
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Shirafuji
authors.forename: Masaki
authors.initials: M
authors.lastname: Otsuka
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamasaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Asagoe
authors.forename: Naohito
authors.initials: N
authors.lastname: Hatta
authors.forename: Keiji
authors.initials: K
authors.lastname: Iwatsuki
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000032:analysis / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D056484:Jumonji Domain-Containing Histone Demethylases / Q000032:analysis / Q000235:genetics; D058965:MART-1 Antigen / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000473:pathology*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics; D021701:Sentinel Lymph Node Biopsy
chemical_list: C480744:ABCB5 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015415:Biomarkers; D058965:MART-1 Antigen; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human