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

研究成果: Article

122 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)2671-2680
ページ数10
ジャーナルJournal of Clinical Oncology
22
発行部数13
DOI
出版物ステータスPublished - 2004
外部発表Yes

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Paraffin
Melanoma
MART-1 Antigen
Odds Ratio
Transcription Factor 3
Sentinel Lymph Node
Recurrence
Neoplasm Micrometastasis
Messenger RNA
Survival
Homeobox Genes
Hematoxylin
Eosine Yellowish-(YS)
Transferases
Lymph Node Excision
Reverse Transcriptase Polymerase Chain Reaction
Proportional Hazards Models
Genes
Statistical Factor Analysis
Multivariate Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

これを引用

Takeuchi, H., Morton, D. L., Kuo, C., Turner, R. R., Elashoff, D., Elashoff, R., ... 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

Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients. / Takeuchi, Hiroya; Morton, Donald L.; Kuo, Christine; Turner, Roderick R.; Elashoff, David; Elashoff, Robert; Taback, Bret; Fujimoto, Akihide; Hoon, Dave S B.

:: Journal of Clinical Oncology, 巻 22, 番号 13, 2004, p. 2671-2680.

研究成果: Article

Takeuchi, H, Morton, DL, Kuo, C, Turner, RR, Elashoff, D, Elashoff, R, Taback, B, Fujimoto, A & Hoon, DSB 2004, 'Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients', Journal of Clinical Oncology, 巻. 22, 番号 13, pp. 2671-2680. https://doi.org/10.1200/JCO.2004.12.009
Takeuchi, Hiroya ; Morton, Donald L. ; Kuo, Christine ; Turner, Roderick R. ; Elashoff, David ; Elashoff, Robert ; Taback, Bret ; Fujimoto, Akihide ; Hoon, Dave S B. / Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients. :: Journal of Clinical Oncology. 2004 ; 巻 22, 番号 13. pp. 2671-2680.
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title = "Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients",
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.",
author = "Hiroya Takeuchi and Morton, {Donald L.} and Christine Kuo and Turner, {Roderick R.} and David Elashoff and Robert Elashoff and Bret Taback and Akihide Fujimoto and Hoon, {Dave S B}",
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T1 - Prognostic significance of molecular upstaging of paraffin-embedded sentinel lymph nodes in melanoma patients

AU - Takeuchi, Hiroya

AU - Morton, Donald L.

AU - Kuo, Christine

AU - Turner, Roderick R.

AU - Elashoff, David

AU - Elashoff, Robert

AU - Taback, Bret

AU - Fujimoto, Akihide

AU - Hoon, Dave S B

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N2 - 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.

AB - 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.

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