title: Prognostic significance of molecular staging study of sentinel lymph nodes by reverse transcriptase-polymerase chain reaction for tyrosinase in melanoma patients.
abstract: BACKGROUND
  We performed this study to evaluate the clinical effect of microscopic and submicroscopic metastases in sentinel lymph nodes (SLNs) from patients with early-stage melanoma.
  
  
  METHODS
  Patients with confirmed cutaneous melanoma (American Joint Committee on Cancer stages I and II) underwent standard lymphoscintigraphy and SLN biopsy. Serial sections were divided between routine histopathology with hematoxylin and eosin plus immunohistochemistry for HMB-45 and molecular analysis by nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase (using beta-actin as a control).
  
  
  RESULTS
  Of 180 patients analyzed (318 SLNs), 38 (21%) patients had positive SLN(s) by routine hematoxylin and eosin and immunohistochemistry (microscopic disease; group 1), and 142 (79%) had negative histological results. Analysis by RT-PCR detected tyrosinase in at least 1 SLN from 124 (69%) patients. Among patients with histologically negative SLN(s), tyrosinase was detected in 86 (48%) patients (submicroscopic disease; group 2), whereas 40 (22%) patients had negative results by both histology and RT-PCR (group 3). Sixteen (9%) patients had histologically negative SLNs and ambiguous RT-PCR results (group 4). Among 138 patients in the analysis of recurrence (mean follow-up, 45 months), only 18 patients had a recurrence: 11 (31%) of 35 in group 1, 5 (10%) of 51 in group 2, and 2 (5%) of 37 in group 3. No recurrences were seen in group 4. Only group 1 had a significantly shorter disease-free survival and overall survival compared with the other groups.
  
  
  CONCLUSIONS
  After a long follow-up period, molecular upstaging by tyrosinase RT-PCR failed to detect a subgroup of patients with an increased probability of recurrence.
authors.affiliation: Department of Dermatology, Hospital Universitario Germans Trias i Pujol, Carretera Canyet s/n., 08916, Badalona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mangas
authors.forename: Josep M
authors.initials: JM
authors.lastname: Hilari
authors.forename: Cristina
authors.initials: C
authors.lastname: Paradelo
authors.forename: Jordi
authors.initials: J
authors.lastname: Rex
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Fernández-Figueras
authors.forename: Manel
authors.initials: M
authors.lastname: Fraile
authors.forename: Antoni
authors.initials: A
authors.lastname: Alastrue
authors.forename: Carlos
authors.initials: C
authors.lastname: Ferrándiz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008297:Male; D008545:Melanoma / Q000201:enzymology / Q000235:genetics* / Q000556:secondary; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014442:Monophenol Monooxygenase