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

AbstractPURPOSE:
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), GalNAc-T (beta1-->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 > or = 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.
AuthorsHiroya Takeuchi, Donald L Morton, Christine Kuo, Roderick R Turner, David Elashoff, Robert Elashoff, Bret Taback, Akihide Fujimoto, Dave S B Hoon
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 13 Pg. 2671-80 (Jul 01 2004) ISSN: 0732-183X [Print] United States
PMID15226334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Genetic Markers
  • RNA, Messenger
Topics
  • Adult
  • Aged
  • Female
  • Genetic Markers
  • Humans
  • Lymphatic Metastasis (diagnosis)
  • Male
  • Melanoma (genetics, pathology)
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger (analysis)
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Sentinel Lymph Node Biopsy
  • Skin Neoplasms (genetics, pathology)
  • Specimen Handling

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