title: Tyrosinase-related protein 1 mRNA expression in lymph node metastases predicts overall survival in high-risk melanoma patients.
abstract: BACKGROUND
  Clinical outcome of high-risk melanoma patients is not reliably predicted from histopathological analyses of primary tumours and is often adjusted during disease progression. Our study aimed at extending our previous findings in skin metastases to evaluate the prognostic value of tyrosinase-related protein 1 (TYRP1) in lymph node metastases of stages III and IV melanoma patients.
  
  
  METHODS
  TYRP1 mRNA expression in 104 lymph node metastases was quantified by real-time PCR and normalised to S100 calcium-binding protein B (S100B) mRNA expression to correct for tumour load. TYRP1/S100B ratios were calculated and median was used as cutoff value. TYRP1/S100B mRNA values were correlated to clinical follow-up and histopathological characteristics of the primary lesion.
  
  
  RESULTS
  A high TYRP1/S100B mRNA ratio significantly correlated with reduced disease-free (DFS) and overall survival (OS; Cox regression analysis, P=0.005 and 0.01, respectively), increased Breslow thickness (Spearman's rho test, P<0.001) and the presence of ulceration (Mann-Whitney test, P=0.02) of the primaries. Moreover, high TYRP1/S100B was of better prognostic value (lower P-value) for OS than Breslow thickness and ulceration. Finally, it was well conserved during disease progression with respect to high/low TYRP1 groups.
  
  
  CONCLUSIONS
  High TYRP1/S100B mRNA expression in lymph node metastases from melanoma patients is associated with unfavourable clinical outcome. Its evaluation in lymph node metastases may refine initial prognosis for metastatic patients, may define prognosis for those with unknown or non-evaluable primary lesions and may allow different management of the two groups of patients.
authors.affiliation: Laboratoire d'Oncologie et de Chirurgie Expérimentale, Institut Jules Bordet, Université Libre de Bruxelles, B1000 Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: El Hajj
authors.forename: F
authors.initials: F
authors.lastname: Journe
authors.forename: M
authors.initials: M
authors.lastname: Wiedig
authors.forename: I
authors.initials: I
authors.lastname: Laios
authors.forename: F
authors.initials: F
authors.lastname: Salès
authors.forename: M-D
authors.initials: MD
authors.lastname: Galibert
authors.forename: L C
authors.initials: LC
authors.lastname: Van Kempen
authors.forename: A
authors.initials: A
authors.lastname: Spatz
authors.forename: B
authors.initials: B
authors.lastname: Badran
authors.forename: D
authors.initials: D
authors.lastname: Larsimont
authors.forename: A
authors.initials: A
authors.lastname: Awada
authors.forename: G
authors.initials: G
authors.lastname: Ghanem
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000235:genetics; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000096:biosynthesis / Q000235:genetics; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; D010088:Oxidoreductases; C489799:TYRP1 protein, human