Prediction of disease outcome in melanoma patients by molecular analysis of paraffin-embedded sentinel lymph nodes

Christine T. Kuo, Dave S B Hoon, Hiroya Takeuchi, Roderick Turner, He Jing Wang, Donald L. Morton, Bret Taback

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Purpose: A significant number of patients who develop recurrence after a histopathologically negative sentinel lymph node (SLN) biopsy will demonstrate occult metastases on re-evaluation of the SLNs with serial sectioning and immunohistochemistry. Reverse transcriptase polymerase chain reaction (RT-PCR) has been evaluated to improve disease staging and avoid false-negative findings in fresh or frozen-section SLNs. The purpose of this study was to develop a multimarker RT-PCR assay for assessing melanoma patients' archived paraffin-embedded (PE) SLNs. Patients and Methods: Archived PE histopathologically positive (n = 37) and negative (n = 40) SLNs from patients with primary melanoma were analyzed using a semiquantitative multimarker RT-PCR assay. Results: Marker expression in histopathologically positive and negative SLNs were as follows: 89%, 92%, 35%, and 43% (positive) and 40%, 33%, 5%, and 13% (negative) for tyrosinase, melanoma antigen recognized by T cells-1, tyrosinase-related protein-1, and tyrosinase-related protein-2, respectively. Twenty-five percent of histopathologically negative SLN patients were upstaged using at least two markers. Of these, 80% developed a recurrence. Furthermore, at a median follow-up of 55 months, patients with histopathologically negative SLNs who expressed zero or one marker had a significantly improved disease-free (P < .002) and overall (P < .03) survival versus those expressing two or more markers. Conclusion: These findings demonstrate the feasibility of a multimarker RT-PCR assay for evaluating archived PE SLNs. More significantly, identification of molecular risk factors can be detected in histopathologically negative SLNs for distinguishing early-stage melanoma patients with a worse prognosis.

Original languageEnglish
Pages (from-to)3566-3572
Number of pages7
JournalJournal of Clinical Oncology
Volume21
Issue number19
DOIs
Publication statusPublished - 2003 Oct 1
Externally publishedYes

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Paraffin
Melanoma
Reverse Transcriptase Polymerase Chain Reaction
MART-1 Antigen
Recurrence
Sentinel Lymph Node Biopsy
Monophenol Monooxygenase
Frozen Sections
Sentinel Lymph Node
Immunohistochemistry
Neoplasm Metastasis
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kuo, C. T., Hoon, D. S. B., Takeuchi, H., Turner, R., Wang, H. J., Morton, D. L., & Taback, B. (2003). Prediction of disease outcome in melanoma patients by molecular analysis of paraffin-embedded sentinel lymph nodes. Journal of Clinical Oncology, 21(19), 3566-3572. https://doi.org/10.1200/JCO.2003.01.063

Prediction of disease outcome in melanoma patients by molecular analysis of paraffin-embedded sentinel lymph nodes. / Kuo, Christine T.; Hoon, Dave S B; Takeuchi, Hiroya; Turner, Roderick; Wang, He Jing; Morton, Donald L.; Taback, Bret.

In: Journal of Clinical Oncology, Vol. 21, No. 19, 01.10.2003, p. 3566-3572.

Research output: Contribution to journalArticle

Kuo, CT, Hoon, DSB, Takeuchi, H, Turner, R, Wang, HJ, Morton, DL & Taback, B 2003, 'Prediction of disease outcome in melanoma patients by molecular analysis of paraffin-embedded sentinel lymph nodes', Journal of Clinical Oncology, vol. 21, no. 19, pp. 3566-3572. https://doi.org/10.1200/JCO.2003.01.063
Kuo, Christine T. ; Hoon, Dave S B ; Takeuchi, Hiroya ; Turner, Roderick ; Wang, He Jing ; Morton, Donald L. ; Taback, Bret. / Prediction of disease outcome in melanoma patients by molecular analysis of paraffin-embedded sentinel lymph nodes. In: Journal of Clinical Oncology. 2003 ; Vol. 21, No. 19. pp. 3566-3572.
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abstract = "Purpose: A significant number of patients who develop recurrence after a histopathologically negative sentinel lymph node (SLN) biopsy will demonstrate occult metastases on re-evaluation of the SLNs with serial sectioning and immunohistochemistry. Reverse transcriptase polymerase chain reaction (RT-PCR) has been evaluated to improve disease staging and avoid false-negative findings in fresh or frozen-section SLNs. The purpose of this study was to develop a multimarker RT-PCR assay for assessing melanoma patients' archived paraffin-embedded (PE) SLNs. Patients and Methods: Archived PE histopathologically positive (n = 37) and negative (n = 40) SLNs from patients with primary melanoma were analyzed using a semiquantitative multimarker RT-PCR assay. Results: Marker expression in histopathologically positive and negative SLNs were as follows: 89{\%}, 92{\%}, 35{\%}, and 43{\%} (positive) and 40{\%}, 33{\%}, 5{\%}, and 13{\%} (negative) for tyrosinase, melanoma antigen recognized by T cells-1, tyrosinase-related protein-1, and tyrosinase-related protein-2, respectively. Twenty-five percent of histopathologically negative SLN patients were upstaged using at least two markers. Of these, 80{\%} developed a recurrence. Furthermore, at a median follow-up of 55 months, patients with histopathologically negative SLNs who expressed zero or one marker had a significantly improved disease-free (P < .002) and overall (P < .03) survival versus those expressing two or more markers. Conclusion: These findings demonstrate the feasibility of a multimarker RT-PCR assay for evaluating archived PE SLNs. More significantly, identification of molecular risk factors can be detected in histopathologically negative SLNs for distinguishing early-stage melanoma patients with a worse prognosis.",
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