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Melanoma-associated Antigens as Messenger RNA Detection Markers for Melanoma¹

John Wayne Cancer Institute at Saint John's Hospital and Health Center, Santa Monica, California 90404 [T. S., D. L. M., D. S. B. H.], and the National Genetics Institute, Los Angeles, California 90064 [D. D. J. C., D. A. G., A. J. C., P. S.]

Melanoma is heterogeneous for its biological properties and melanoma-associated antigens (MAAs). This diversity is partially observed in the expression of the MAAs involved with the melanin synthesis pathway. We therefore developed a sensitive multimarker reverse transcription-PCR plus Southern blot assay using five MAAs as molecular markers to detect primary and metastatic melanoma cells. Melanoma cell lines, melanocytes (cultured), primary and metastatic malignant melanoma tissues, and blood from patients with American Joint Committee on Cancer stage I-IV melanoma were assessed for tyrosinase, tyrosinase-related proteins 1 and 2, Pmel 17, and MART-1/Melan-A. All of the MAA mRNA markers were expressed in 100% of melanoma cell lines and cultured melanocytes, 74% of primary and metastatic tumors (excluding tumor-draining lymph nodes), 43% of tumor-involved lymph nodes, and 43% of patients' bloods. Hypomelanotic melanoma tissues expressed a lower frequency of individual mRNA markers. Overall, at least one mRNA marker was expressed in more than 86% of specimens assayed. Normal tissue specimens from patients and blood from normal volunteer donors were negative for MAA mRNA expression. The multimarker MAA reverse transcription-PCR plus Southern blot analysis was more reliable and sensitive than a single-molecular marker assay for the detection of melanoma cells. This molecular assay can also provide information on MAA mRNA expression of metastatic melanoma cells that may assist in monitoring the therapeutic efficacy of active specific immunotherapy toward specific MAA-bearing melanomas.

¹ Supported in part by Grants PO1 CA1038 and T32 CA 09689 (to T. S.) from the National Cancer Institute.

² To whom requests for reprints should be addressed, at the Division of Molecular Oncology, John Wayne Cancer Institute, 2200 Santa Monica Boulevard, Santa Monica, CA 90404.

Received 10/ 2/96. Accepted 2/ 8/97.

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