title: Molecular Staging of Sentinel Lymph Nodes Identifies Melanoma Patients at Increased Risk of Nodal Recurrence.
abstract: BACKGROUND
  Molecular staging of sentinel lymph nodes (SLNs) may identify patients who are node-negative by standard microscopic staging but are at increased risk for regional nodal recurrence; such patients may benefit from completion lymph node dissection (CLND).
  
  
  METHODS
  In a multicenter, randomized clinical trial, patients with tumor-negative SLNs by standard pathology (hematoxylin and eosin [H and E] serial sections and immunohistochemistry [IHC]) underwent reverse transcriptase polymerase chain reaction (PCR) analysis of SLNs for melanoma-specific mRNA. Microscopically negative/PCR+ patients were randomized to observation, CLND, or CLND with high-dose interferon (HDI). For this post-hoc analysis, clinicopathologic features and survival outcomes, including overall survival (OS) and disease-free survival (DFS), were compared between PCR+ patients who underwent CLND vs observation. Microscopic and molecular node-negative (PCR-) patients were included for comparison.
  
  
  RESULTS
  A total of 556 patients were PCR+: 180 underwent observation, and 376 underwent CLND. An additional 908 PCR- patients were observed. Median follow-up was 72 months. Disease-free survival (DFS) was significantly better for PCR+ patients who underwent CLND compared with observation (p = 0.0218). No statistically significant differences in OS or distant disease-free survival (DDFS) were seen. Regional lymph node recurrence-free survival (LNRFS) was improved in PCR+ patients with CLND compared to observation (p = 0.0065). The PCR+ patients in the observation group had the worst DFS; those with CLND had similar DFS to that in the PCR- group (p = 0.9044).
  
  
  CONCLUSIONS
  Patients with microscopically negative/PCR+ SLN have an increased risk of nodal recurrence that was mitigated by CLND. Although CLND did not affect OS, these data suggest that molecular detection of melanoma-specific mRNA in the SLN predicts a greater risk of nodal recurrence and deserves further study.
authors.affiliation: The Hiram C Polk, Jr, MD Department of Surgery, University of Louisville, Louisville, KY.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Kimbrough
authors.affiliation: The Hiram C Polk, Jr, MD Department of Surgery, University of Louisville, Louisville, KY.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Egger
authors.affiliation: The Hiram C Polk, Jr, MD Department of Surgery, University of Louisville, Louisville, KY.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: McMasters
authors.affiliation: Department of Statistics, University of Kentucky, Lexington, KY.
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Stromberg
authors.affiliation: The Hiram C Polk, Jr, MD Department of Surgery, University of Louisville, Louisville, KY.
authors.forename: Robert C G
authors.initials: RC
authors.lastname: Martin
authors.affiliation: The Hiram C Polk, Jr, MD Department of Surgery, University of Louisville, Louisville, KY.
authors.forename: Prejesh
authors.initials: P
authors.lastname: Philips
authors.affiliation: The Hiram C Polk, Jr, MD Department of Surgery, University of Louisville, Louisville, KY. Electronic address: Charles.Scoggins@louisville.edu.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Scoggins
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D058965:MART-1 Antigen / Q000235:genetics / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000209:etiology*; D009367:Neoplasm Staging / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D057832:Watchful Waiting; D058951:gp100 Melanoma Antigen / Q000235:genetics / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C072013:MAGEA3 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D058951:gp100 Melanoma Antigen; D007372:Interferons; D014442:Monophenol Monooxygenase