title: Gene expression profiling of paraffin-embedded primary melanoma using the DASL assay identifies increased osteopontin expression as predictive of reduced relapse-free survival.
abstract: OBJECTIVE
  Gene expression studies in melanoma have been few because tumors are small and cryopreservation is rarely possible. The purpose of this study was to evaluate the Illumina DASL Array Human Cancer Panel for gene expression studies in formalin-fixed melanoma primary tumors and to identify prognostic biomarkers.
  
  
  METHODS
  Primary tumors from two studies were sampled using a tissue microarray needle. Study 1: 254 tumors from a melanoma cohort recruited from 2000 to 2006. Study 2: 218 tumors from a case-control study of patients undergoing sentinel node biopsy.
  
  
  RESULTS
  RNA was obtained from 76% of blocks; 1.4% of samples failed analysis (transcripts from <250 of the 502 genes on the DASL chip detected). Increasing age of the block and increased melanin in the tumor were associated with reduced number of genes detected. The gene whose expression was most differentially expressed in association with relapse-free survival in study 1 was osteopontin (SPP1; P = 2.11 x 10(-6)) and supportive evidence for this was obtained in study 2 used as a validation set (P = 0.006; unadjusted data). Osteopontin level in study 1 remained a significant predictor of relapse-free survival when data were adjusted for age, sex, tumor site, and histologic predictors of relapse. Genes whose expression correlated most strongly with osteopontin were PBX1, BIRC5 (survivin), and HLF.
  
  
  CONCLUSIONS
  Expression data were obtained from 74% of primary melanomas and provided confirmatory evidence that osteopontin expression is a prognostic biomarker. These results suggest that predictive biomarker studies may be possible using stored blocks from mature clinical trials.
authors.affiliation: Section of Epidemiology and Biostatistics, Leeds Institute of Molecular Medicine, St. James's University Hospital, Leeds, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Conway
authors.forename: Angana
authors.initials: A
authors.lastname: Mitra
authors.forename: Rosalyn
authors.initials: R
authors.lastname: Jewell
authors.forename: Juliette
authors.initials: J
authors.lastname: Randerson-Moor
authors.forename: Samira
authors.initials: S
authors.lastname: Lobo
authors.forename: Jérémie
authors.initials: J
authors.lastname: Nsengimana
authors.forename: Sara
authors.initials: S
authors.lastname: Edward
authors.forename: D Scott
authors.initials: DS
authors.lastname: Sanders
authors.forename: Martin
authors.initials: M
authors.lastname: Cook
authors.forename: Barry
authors.initials: B
authors.lastname: Powell
authors.forename: Andy
authors.initials: A
authors.lastname: Boon
authors.forename: Faye
authors.initials: F
authors.lastname: Elliott
authors.forename: Floor
authors.initials: F
authors.lastname: de Kort
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Knowles
authors.forename: D Timothy
authors.initials: DT
authors.lastname: Bishop
authors.forename: Julia
authors.initials: J
authors.lastname: Newton-Bishop
mesh_terms: D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D015331:Cohort Studies; D015925:Cryopreservation; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D053495:Osteopontin / Q000096:biosynthesis*; D010232:Paraffin / Q000737:chemistry; D012008:Recurrence; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy
chemical_list: D014408:Biomarkers, Tumor; D053495:Osteopontin; D010232:Paraffin