title: Molecular staging of malignant melanoma: correlation with clinical outcome.
abstract: BACKGROUND
  For most solid tumors, the metastatic status of regional lymph nodes is the strongest predictor of relapse and survival. However, routine pathological examination of lymph nodes may underestimate the number of patients with melanoma who have nodal metastases.
  
  
  OBJECTIVE
  To determine the clinical significance of a highly sensitive molecular assay for occult nodal metastases for the staging of patients with melanoma.
  
  
  METHODS
  A prospective cohort study of consecutive patients in which lymphatic mapping and sentinel lymph node (SLN) biopsy were performed on 114 melanoma patients with clinical stage I and stage II disease. The SLNs were bivalved, and half of each specimen was submitted for routine pathological examination. The other half was submitted for molecular detection of submicroscopic metastases using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase messenger RNA as a marker for the presence of melanoma cells. Patient follow-up averaged 28 months.
  
  
  METHODS
  A major university-based melanoma referral center at a National Cancer Institute-designated cancer center.
  
  
  METHODS
  A total of 114 patients with newly diagnosed cutaneous malignant melanoma who were at risk for regional nodal metastases.
  
  
  METHODS
  Melanoma recurrence and overall survival.
  
  
  RESULTS
  Twenty-three patients (20%) had pathologically positive SLNs, and all of these patients were also RT-PCR positive. Of the 91 pathologically negative patients, 44 were RT-PCR negative and 47 were RT-PCR positive. There was a recurrence rate among 14 (61%) of the 23 patients who were both pathologically and RT-PCR positive and a recurrence rate among 1 (2%) of 44 patients who were both pathologically and RT-PCR negative. For patients who were upstaged by the molecular assay (pathologically negative, RT-PCR positive), there was a recurrence rate among 6 (13%) of 47 patients. The differences in recurrence rates and overall survival between the pathologically negative, RT-PCR-negative and pathologically negative, RT-PCR-positive patient groups were statistically significant (P= .02 for disease-free survival and for overall survival). In both univariate and multivariate regression analyses, the histological and RT-PCR status of the SLNs were the best predictors of disease-free survival.
  
  
  CONCLUSIONS
  The use of an RT-PCR assay for detection of submicroscopic melanoma metastases in SLNs improved the prediction of melanoma recurrence and overall survival over routine pathological examination.
authors.affiliation: Cutaneous Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Department of Surgery, University of South Florida, Tampa 33612, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Shivers
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: E
authors.initials: E
authors.lastname: Joseph
authors.forename: J
authors.initials: J
authors.lastname: Messina
authors.forename: L F
authors.initials: LF
authors.lastname: Glass
authors.forename: R
authors.initials: R
authors.lastname: DeConti
authors.forename: C W
authors.initials: CW
authors.lastname: Cruse
authors.forename: C
authors.initials: C
authors.lastname: Berman
authors.forename: N A
authors.initials: NA
authors.lastname: Fenske
authors.forename: G H
authors.initials: GH
authors.lastname: Lyman
authors.forename: D S
authors.initials: DS
authors.lastname: Reintgen
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009367:Neoplasm Staging / Q000379:methods*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis; D011877:Radionuclide Imaging; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D016019:Survival Analysis
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014442:Monophenol Monooxygenase