Prediction of disease outcome in melanoma patients by molecular analysis of paraffin-embedded sentinel lymph nodes

J Clin Oncol. 2003 Oct 1;21(19):3566-72. doi: 10.1200/JCO.2003.01.063. Epub 2003 Aug 11.

Abstract

Purpose: 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.

Patients and 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Female
  • Genetic Markers*
  • Humans
  • Male
  • Melanoma / genetics*
  • Melanoma / pathology*
  • Melanoma / therapy
  • Middle Aged
  • Neoplasm Metastasis
  • Predictive Value of Tests
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sentinel Lymph Node Biopsy*
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / therapy
  • Specimen Handling
  • Treatment Outcome

Substances

  • Genetic Markers