title: Prediction of disease outcome in melanoma patients by molecular analysis of paraffin-embedded sentinel lymph nodes.
abstract: OBJECTIVE
  A significant number of patients who develop recurrence after a histopathologically negative sentinel lymph node (SLN) biopsy will demonstrate occult metastases on re-evaluation of the SLNs with serial sectioning and immunohistochemistry. Reverse transcriptase polymerase chain reaction (RT-PCR) has been evaluated to improve disease staging and avoid false-negative findings in fresh or frozen-section SLNs. The purpose of this study was to develop a multimarker RT-PCR assay for assessing melanoma patients' archived paraffin-embedded (PE) SLNs.
  
  
  METHODS
  Archived PE histopathologically positive (n = 37) and negative (n = 40) SLNs from patients with primary melanoma were analyzed using a semiquantitative multimarker RT-PCR assay.
  
  
  RESULTS
  Marker expression in histopathologically positive and negative SLNs were as follows: 89%, 92%, 35%, and 43% (positive) and 40%, 33%, 5%, and 13% (negative) for tyrosinase, melanoma antigen recognized by T cells-1, tyrosinase-related protein-1, and tyrosinase-related protein-2, respectively. Twenty-five percent of histopathologically negative SLN patients were upstaged using at least two markers. Of these, 80% developed a recurrence. Furthermore, at a median follow-up of 55 months, patients with histopathologically negative SLNs who expressed zero or one marker had a significantly improved disease-free (P <.002) and overall (P <.03) survival versus those expressing two or more markers.
  
  
  CONCLUSIONS
  These findings demonstrate the feasibility of a multimarker RT-PCR assay for evaluating archived PE SLNs. More significantly, identification of molecular risk factors can be detected in histopathologically negative SLNs for distinguishing early-stage melanoma patients with a worse prognosis.
authors.affiliation: Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404, USA.
authors.forename: Christine T
authors.initials: CT
authors.lastname: Kuo
authors.forename: Dave S B
authors.initials: DS
authors.lastname: Hoon
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Roderick
authors.initials: R
authors.lastname: Turner
authors.forename: He-Jing
authors.initials: HJ
authors.lastname: Wang
authors.forename: Donald L
authors.initials: DL
authors.lastname: Morton
authors.forename: Bret
authors.initials: B
authors.lastname: Taback
mesh_terms: D000328:Adult; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D013048:Specimen Handling; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers