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), 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.
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Authors | Hiroya Takeuchi, Donald L Morton, Christine Kuo, Roderick R Turner, David Elashoff, Robert Elashoff, Bret Taback, Akihide Fujimoto, Dave S B Hoon |
Journal | Journal 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 |
PMID | 15226334
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Genetic Markers
- RNA, Messenger
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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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