title: Tissue microarray analysis of methylthioadenosine phosphorylase protein expression in melanocytic skin tumors.
abstract: BACKGROUND
  Using tissue microarrays, we investigated whether methylthioadenosine phosphorylase (MTAP) protein expression is associated with clinicopathologic variables in benign and malignant melanocytic skin tumors.
  
  
  METHODS
  Cytoplasmic MTAP expression was detected in 227 (72.1%) of 315 informative cases. Expression was significantly reduced in primary malignant melanomas and in melanoma metastases compared with benign nevi (P<.001 for both). No difference was noted in MTAP expression between primary malignant melanomas and melanoma metastases. In primary malignant melanomas, a Ki67-labeling index less than 5% was associated with MTAP expression (P = .04), suggesting that loss of MTAP expression is associated with proliferation. No other variables had significant associations with MTAP expression. Lymph node metastases demonstrated significantly higher MTAP expression compared with skin metastases (P = .01). In the overall cohort, MTAP expression was not associated with prognosis. Among 26 patients with MTAP-positive melanomas and tumor recurrence, 18 patients who received interferon therapy had a significant benefit compared with 8 patients who did not receive interferon therapy (P = .009). This was not seen in the patients with MTAP-negative tumors. Conclusion Methylthioadenosine phosphorylase protein expression may be a predictive marker of interferon therapy resistance in patients with melanoma and disease progression.
authors.affiliation: Institute of Pathology and Department of Dermatology, University of Regensburg, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
authors.forename: Stefanie
authors.initials: S
authors.lastname: Meyer
authors.forename: Frauke
authors.initials: F
authors.lastname: Bataille
authors.forename: Matthias
authors.initials: M
authors.lastname: Woenckhaus
authors.forename: Markus
authors.initials: M
authors.lastname: Ameres
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogt
authors.forename: Michael
authors.initials: M
authors.lastname: Landthaler
authors.forename: Armin
authors.initials: A
authors.lastname: Pauer
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; D016022:Case-Control Studies; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D046228:Microarray Analysis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D011683:Purine-Nucleoside Phosphorylase / Q000378:metabolism*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D007372:Interferons; D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase