Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients

Hiroya Takeuchi, Donald L. Morton, Christine Kuo, Roderick R. Turner, David Elashoff, Robert Elashoff, Bret Taback, Akihide Fujimoto, Dave S.B. Hoon

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124 Citations (Scopus)

Abstract

Purpose: Detection of micrometastases in sentinel lymph nodes (SLNs) is important for accurate staging and prognosis in melanoma patients. However, a significant number of patients with histopathology-negative SLNs subsequently develop recurrent disease. We hypothesized that a quantitative realtime reverse transcriptase polymerase chain reaction (qRT) assay using multiple specific mRNA markers could detect occult metastasis in paraffin-embedded (PE) SLNs to upstage and predict disease outcome. Patients and Methods: qRT was performed on retrospectively collected PE SLNs from 215 clinically node-negative patients who underwent lymphatic mapping and sentinel lymphadenectomy for melanoma and were followed up for at least 8 years. PE SLNs (n = 308) from these patients were sectioned and assessed by qRT for mRNA of four melanoma-associated genes: MART-1 (antigen recognized by T cells-1), MAGE-A3 (melanoma antigen gene-A3 family). GaINAc-T (β1→4-N-acetylgalactosaminyl-transferase), and Pax3 (paired-box homeotic gene transcription factor 3). Results: Fifty-three (25%) patients had histopathology-positive SLNs by hemotoxylin and eosin and/or immunohistochemistry. Of the 162 patients with histopathology-negative SLNs, 48 (30%) had nodes that expressed at least one of the four qRT markers, and these 48 patients also had a significantly increased risk of disease recurrence by a Cox proportional hazards model analysis (P < .0001; risk ratio, 7.48; 95% CI, 3.70 to 15.15). The presence of ≥ one marker in histopathology-negative SLNs was also a significant independent prognostic factor by multivariate analysis for overall survival (P = .0002; risk ratio, 11.42; 95% CI, 3.17 to 41.1). Conclusion: Molecular upstaging of PE histopathology-negative SLNs by multiple-marker qRT assay is a significant independent prognostic factor for long-term disease recurrence and overall survival of patients with early-stage melanoma.

Original languageEnglish
Pages (from-to)2671-2680
Number of pages10
JournalJournal of Clinical Oncology
Volume22
Issue number13
DOIs
Publication statusPublished - 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Takeuchi, H., Morton, D. L., Kuo, C., Turner, R. R., Elashoff, D., Elashoff, R., Taback, B., Fujimoto, A., & Hoon, D. S. B. (2004). Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients. Journal of Clinical Oncology, 22(13), 2671-2680. https://doi.org/10.1200/JCO.2004.12.009