title: Methylthioadenosine phosphorylase represents a predictive marker for response to adjuvant interferon therapy in patients with malignant melanoma.
abstract: Using tissue microarrays assembling 465 nevi, primary melanomas and metastases, we investigated whether expression of methylthioadenosine phosphorylase (MTAP), a recently suggested biomarker of malignant melanoma, has prognostic significance and may predict responsiveness to adjuvant interferon therapy in patients with melanoma. Because of its association with MTAP activity and interferon signalling pathways, signal transducer and activator of transcription 1 (STAT1) immunohistochemistry was analysed, too. MTAP expression was significantly reduced in melanomas and metastases compared with nevi (P < 0.001); STAT1 expression significantly increased. In melanomas, loss of MTAP expression was significantly related to Clark level (P < 0.05) and tumor thickness (P < 0.01); whereas STAT1 immunoreactivity was significantly related to gender (p < 0.05) and tumor thickness (P < 0.05). Interestingly, subgroup analysis of patients with a tumor thickness of 1.5-4.0 mm revealed a significant survival benefit from adjuvant interferon treatment regarding recurrence-free survival (RFS; P < 0.05) if MTAP expression was observed in the primary melanoma. Patients with STAT1-positive melanomas also tended to benefit from interferon concerning RFS (P = 0.074) and showed a significant benefit concerning overall survival (OS; P < 0.05). According to Cox analysis, MTAP expression in contrast to STAT1 was an independent positive prognostic marker for RFS and OS. In conclusion, MTAP represents a highly promising immunohistochemical marker for prognosis and interferon response of patients with malignant melanoma.
authors.affiliation: Department of Dermatology, University Hospital of Regensburg, Regensburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Meyer
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogt
authors.forename: Frauke
authors.initials: F
authors.lastname: Bataille
authors.forename: Christoph
authors.initials: C
authors.lastname: Ehret
authors.forename: Susanne
authors.initials: S
authors.lastname: Gantner
authors.forename: Michael
authors.initials: M
authors.lastname: Landthaler
authors.forename: Monika
authors.initials: M
authors.lastname: Klinkhammer-Schalke
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstaedter
authors.forename: Anja K
authors.initials: AK
authors.lastname: Bosserhoff
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis / Q000188:drug therapy; D009506:Nevus / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D011379:Prognosis; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism*; D012189:Retrospective Studies; D050794:STAT1 Transcription Factor / Q000378:metabolism; D012878:Skin Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007372:Interferons; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase