Originally published as JCO Early Release 10.1200/JCO.2003.01.063 on August 11 2003

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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

From the Department of Molecular Oncology, Department of Pathology, Division of Biostatistics, and Department of Surgical Oncology, John Wayne Cancer Institute, St John’s Health Center, Santa Monica, CA.

Address reprint requests to Bret Taback, MD, Department of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404; e-mail: tabackb{at}jwci.org.

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.

Supported in part by National Institutes of Health grants NCI P01 CA29605 and P01 CA12582, and the Roy E. Coats Research Laboratories of the John Wayne Cancer Institute.

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