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Previous Volume 328:1302-1307 May 6, 1993 Number 18 Next

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ABSTRACT

Background and Methods The lesions of cutaneous mastocytosis are characterized by dermal infiltrates of mast cells and may appear hyperpigmented because of the presence of increased levels of epidermal melanin. Mast-cell growth factor, the ligand for the product of the c-kit proto-oncogene, stimulates the proliferation of mast cells and increases the production of melanin by melanocytes. We therefore looked for the expression of the mast-cell growth factor gene in the skin of patients with cutaneous mastocytosis using immunohistochemical techniques and the polymerase chain reaction.

Results In the skin of normal subjects and those with unrelated diseases, immunoreactive mast-cell growth factor was associated with keratinocytes and scattered dermal cells, a pattern consistent with cell-bound mast-cell growth factor. In skin samples containing lesions and in clinically normal skin from patients with mastocytosis, however, mast-cell growth factor was also found free in the dermis and in the extracellular spaces between keratinocytes, suggesting the presence of a soluble form of this protein. Messenger RNA (mRNA) that can encode soluble mast-cell growth factor was present in the skin of patients as well as in that of normal control subjects. No sequence abnormalities were detected in mRNA for mast-cell growth factor from one patient.

Conclusions The altered distribution of mast-cell growth factor in the skin of patients with cutaneous mastocytosis is consistent with abnormal production of the soluble form of this factor. This abnormality is probably due to increased proteolytic processing, since it was not explained by differences in the splicing or sequence of mast-cell growth factor mRNA in the patients. Soluble mast-cell growth factor may cause the characteristic accumulation of mast cells and the hyperpigmentation of skin found in cutaneous mastocytosis. These findings suggest that some forms of mastocytosis represent reactive hyperplasia rather than mast-cell neoplasia.

Source Information

From the Department of Dermatology (B.J.L., G.S.M., L.T., T.G.D., R.H.) and the Section of Dermatopathology (B.J.L., L.T.), Yale University School of Medicine, New Haven, Conn., and the Departments of Molecular Biology (D.M.A.) and Experimental Hematology (D.E.W.), Immunex Corporation, Seattle.

Address reprint requests to Dr. Longley at Yale University School of Medicine, Department of Dermatology, 333 Cedar St., P.O. Box 3333, LCI 500, New Haven, CT 06510.

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