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Expression of Mutant p53 in Melanoma¹

Nuffield Department of Surgery, University of Oxford, Radcliffe Infirmary, Oxford OX2 6HE, UK [J. R. S.], Nuffield Department of Pathology, University of Oxford, Oxford OX3 9DU, UK [K. C. G.], Department of Pathology, Rigshospitalet, University of Copenhagen, Copenhagen DK 2100, Denmark [E. R.], Cell Transformation Research Group, Cancer Research Campaign Laboratories, Department of Biochemistry, University of Dundee, Dundee DD1 4HN, UK [D. P. L.], and University of Oxford, Molecular Oncology Laboratory, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK [A. L. H.]

Mutant p53 has been noted in a variety of human malignancies including carcinomas of lung, breast, and colon, which have also been reported to have frequent karyotype anomalies involving the locus of the p53 gene (17p13). Whereas chromosomal abnormalities of chromosomes 1, 6, and 7 have been noted previously in melanoma, frequent aberrations in chromosome 17 have not been reported previously. Due to the common mutation of this locus in so many types of neoplasms, a range of melanomas from different stages of tumor progression were examined immunohistochemically for expression of mutant p53, in order to assess its prevalence and consider the role of this oncogene in the biological progression of melanoma. Forty-five of 53 (85%) specimens from a range of primary and metastatic melanomas were found to have detectable evidence of p53 gene mutation, by virtue of the immunohistochemical detection of mutant p53 protein. Significantly increased prevalence of mutant p53 was found in metastatic melanoma, compared with primary tumors (P < 0.05). These findings represent one of the highest incidences of this oncogenic mutation yet recorded in a human malignancy and support the concept that p53 may have a functional role in development of the metastatic tumor phenotype.

¹ This work has been funded by the Medical Research Fund of Oxford University and the support is gratefully acknowledged. Additional support has been provided from the Jill Broadis Trust for Cancer Research, Stuart Milton Trust, and the Plastic Surgery Research Fund. J. R. S. holds an Overseas Research Student Award at the University of Oxford.

² To whom requests for reprints should be addressed.

Received 5/28/91. Accepted 8/19/91.

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