Further evidence that acanthosis nigricans maligna is linked to enhanced secretion by the tumour of transforming growth factor alpha

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Abstract
The pathogenesis of cutaneous paraneoplastic syndromes is still under discussion. Since many of these syndromes, including acanthosis nigricans, are proliferative skin disorders it is believed that products secreted by the tumour stimulate the keratinocytes to proliferate. Growth factors like transforming growth factor alpha (TGF-alpha) are known to be highly mitogenic for keratinocytes in vitro. Here we report on a patient with a poorly differentiated gastric cancer and a full clinical picture of acanthosis nigricans characterized by diffuse hyperkeratosis and multiple papillomatous lesions of the skin with involvement of the conjunctivae. In Southern blot analysis of the tumour tissue from this patient amplification of the epidermal growth factor (EGF) receptor, the common ligand for TGF-alpha and EGF, was shown. Immunohistochemically, prominent staining was found throughout the tumour using anti-TGF-alpha antibodies. In a series of 25 investigated gastric tumour biopsies, four tumours showed amplification of the EGF receptor and one additional biopsy was positive for TGF-alpha. Since there is no other report describing the link between TGF-alpha and acanthosis nigricans, except that of Ellis et al. 1987, we present a new case suggesting a possible link between growth factors and acanthosis nigricans maligna.