Molecular upstaging based on paraffin-embedded sentinel lymph nodes: ten-year follow-up confirms prognostic utility in melanoma patients

Ann Surg. 2011 Jan;253(1):116-22. doi: 10.1097/SLA.0b013e3181fca894.

Abstract

Objective: To determine the long-term clinical significance of molecular upstaging in histopathology-negative, paraffin-embedded (PE) sentinel lymph nodes (SLNs) from melanoma patients.

Background: Histopathologic evaluation can miss clinically relevant melanoma micrometastases in SLNs. This longitudinal correlative study is the first 10-year prognostic evaluation of a multimarker quantitative real-time reverse transcriptase-polymerase chain reaction (qRT) assay for PE melanoma-draining SLNs.

Methods: The SLN sections (n = 214) were assessed by qRT assay for 4 established messenger RNA biomarkers: MART-1, MAGE-A3, GalNAc-T, and PAX3.

Results: The qRT assay upstaged 48 of 161 histopathology-negative (hematoxylin-eosin and immunohistochemistry) SLN specimens. At a median follow-up of 11.3 years for the entire cohort, estimated rates of 10-year overall survival (OS) and melanoma-specific survival (MSS) were 82% and 94%, respectively, for histopathology-negative/qRT-negative patients; 56% and 61%, respectively, for histopathology-positive patients; and 52% and 60%, respectively, for histopathology-negative/qRT-positive patients (P < 0.001 for OS, P < 0.001 for MSS). In a multivariate analysis of known melanoma prognostic factors, qRT positivity was significant (P < 0.05) for disease-free survival (hazard ratio [HR], 4.3; 95% confidence interval (CI), 2.3-7.8), distant disease-free survival (HR, 6.6; 95% CI, 2.9-14.6), MSS (HR, 6.2; 95% CI, 2.6-14.4), and OS (HR, 2.8; 95% CI, 1.6-4.9).

Conclusion: The multimarker qRT assay has prognostic significance for molecular upstaging of PE melanoma-draining SLNs. Molecular upstaging of histopathology-negative SLNs confers a prognosis similar to that associated with SLN micrometastasis, and the number of positive qRT biomarkers is correlated to disease outcome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Female
  • Humans
  • Longitudinal Studies
  • MART-1 Antigen / genetics
  • MART-1 Antigen / metabolism*
  • Male
  • Melanoma / metabolism
  • Melanoma / secondary*
  • Melanoma / surgery
  • Middle Aged
  • N-Acetylgalactosaminyltransferases / genetics
  • N-Acetylgalactosaminyltransferases / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Neoplasm Staging
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Paired Box Transcription Factors / metabolism*
  • Paraffin Embedding
  • Polypeptide N-acetylgalactosaminyltransferase
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sentinel Lymph Node Biopsy
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / surgery
  • Survival Analysis

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • MAGEA3 protein, human
  • MART-1 Antigen
  • Neoplasm Proteins
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • RNA, Messenger
  • N-Acetylgalactosaminyltransferases