title: Cisplatin fails to induce puma mediated apoptosis in mucosal melanomas.
abstract: OBJECTIVE
  Mucosal melanomas (MM) are aggressive subtypes of common melanomas. It remains unclear whether limitations in their resectability or their distinctive molecular mechanisms are responsible for the aggressive phenotype.
  
  
  METHODS
  In total, 112 patients with cutaneous melanomas (CM) and 27 patients with MM were included. Clinical parameters were analysed using Chi square, Fisher exact and student's t-test. Survival rates were calculated by Kaplan-Meier. Analysis of p53, p21, Mdm2, Hipk2, Gadd45, Puma, Bax, Casp9 and Cdk1 via quantitative PCR and immunohistochemistry (IHC) was performed. TP53 induction after cisplatin treatment was analysed in 10 cell lines (melanocytes, four MM and five CM) using western blot (WB) and qPCR.
  
  
  RESULTS
  The overall/recurrence-free survival differed significantly between MM (40 months and 30 months) and CM (90 months and 107 months; p < 0.001). IHC and WB confirmed high p53 expression in all melanomas. Hipk2 and Gadd45 showed significantly higher expressions in CM (p < 0.005; p = 0.004). QPCR and WB of wild-type cell lines demonstrated no differences for p53, p21, Mdm2, Bax and Casp9. WB failed to detect Puma in MM, while Cdk1 regulation occurred exclusively in MM.
  
  
  CONCLUSIONS
  The aggressive phenotype of MM did not appear to be due to differential expressions of p53, p21, Mdm2, Bax or Casp9. A non-functional apoptosis in MM may have further clinical implications.
authors.affiliation: Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany.
authors.forename: Marie Kristin
authors.initials: MK
authors.lastname: Fritsche
authors.affiliation: Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany.
authors.forename: Veronika
authors.initials: V
authors.lastname: Metzler
authors.affiliation: Universität München, Institut für Allgemeine Pathologie und Pathologische Anatomie, 81675 München, Germany.
authors.forename: Karen
authors.initials: K
authors.lastname: Becker
authors.affiliation: Heinrich Heine Universität Düsseldorf, Hals-Nasen-Ohrenklinik, 40225 Düsseldorf, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Plettenberg
authors.affiliation: Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Heiser
authors.affiliation: Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Hofauer
authors.affiliation: Technische Universität München, Hals-Nasen-Ohrenklinik und Poliklinik, 81675 München, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Knopf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D016203:CDC2 Protein Kinase; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008544:Melanocytes / Q000166:cytology; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism*; D008875:Middle Aged; D009092:Mucous Membrane / Q000473:pathology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012878:Skin Neoplasms; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D002945:Cisplatin
keywords: cell-cycle; melanoma; p53; sinonasal; survival
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