title: TYRP1 mRNA expression in melanoma metastases correlates with clinical outcome.
abstract: BACKGROUND
  Clinical outcome of patients with high-risk melanoma cannot be reliably predicted on the basis of classical histopathological examination. Our study aimed to determine in melanoma metastases a gene expression profile associated with patient survival, and to identify and validate marker(s) of poor clinical outcome.
  
  
  METHODS
  Skin and lymph node metastases from melanoma patients (training population) were used to identify candidate prognostic marker(s) based on DNA microarray analysis. Additional skin metastases (validation population) were used to assess the prognostic value of the first ranked gene by real-time PCR.
  
  
  RESULTS
  We performed microarray analysis in the training population and generated a list of 278 probe sets associated with a shorter survival. We used the first ranked gene, tyrosinase-related protein 1 (TYRP1), further measured its expression in the validation population by real-time PCR and found it to be significantly correlated with distant metastasis-free survival (DMFS), overall survival (OS) and Breslow thickness. We also found that it was fairly well conserved in the course of the disease regardless of the delay to metastasis occurrence. Finally, although Tyrp1 protein (immunohistochemistry (IHC)) was only detected in about half of the samples, we showed that its expression also correlated with Breslow thickness.
  
  
  CONCLUSIONS
  Our data indicate that TYRP1 mRNA expression level, at least in skin metastases, is a prognostic marker for melanoma, and is particularly useful when prognostic pathology parameters at the primary lesion are lacking. Its conserved expression further supports its use as a target for therapy.
authors: Laboratoire d'Oncologie et de Chirurgie Expérimentale, Institut Jules Bordet, Université Libre de Bruxelles, 1 rue Heger-Bordet, Brussels, Belgium.
authors: F
authors: F
authors: Journe
authors: H
authors: H
authors: Id Boufker
authors: L
authors: L
authors: Van Kempen
authors: M-D
authors: MD
authors: Galibert
authors: M
authors: M
authors: Wiedig
authors: F
authors: F
authors: Salès
authors: A
authors: A
authors: Theunis
authors: D
authors: D
authors: Nonclercq
authors: A
authors: A
authors: Frau
authors: G
authors: G
authors: Laurent
authors: A
authors: A
authors: Awada
authors: G
authors: G
authors: Ghanem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010088:Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D010088:Oxidoreductases; C489799:TYRP1 protein, human