Expression of the Sonic Hedgehog receptor 'PATCHED' in basal cell carcinomas and odontogenic keratocysts

Basal cell carcinoma (BCC) is a common invasive skin lesion in Caucasians. keratocysts (OKs) are developmental, non-inflammatory oral cysts. They can be sporadic and/or multiple and are locally destructive. Basal cell naevus syndrome (BCNS) comprises both multiple BCCs and multiple OKs, in addition to several other systemic manifestations. The genetic defect underlying thi s autosomal dominant syndrome is a germ line mutation in the Sonic Hedgehog receptor PATCHED (PTCH) gene. For this study, a rabbit anti-peptide PTCH a ntiserum was produced. Immunohistochemistry procedures were performed using PTCH antibody and commercially produced GLI-I antibody (downstream member in the hedgehog pathway) to stain 11 BCNS-OKs, eight sporadic OKs, two BCNS -BCCs, and six sporadic BCCs. Most of these lesions had been previously scr eened for PTCH mutation. Most BCCs (n = 7) demonstrated moderate staining, with the heaviest staining in the outer palisading cell laver, except a BCN S-BCC which had mutation proximal to the sequence used for production of im munogenic peptide; this demonstrated only weak staining. Although moderate to heavy staining with PTCH antibody was demonstrated in the epithelium of both types of OK (n = 19), a quite different pattern of staining of the bas al cell layer was observed in the two patient groups. In BCNS, OK staining was heaviest in basal epithelial layers. In contrast, staining in non-BCNS odontogenic keratocysts was exclusively located in the superficial epitheli al layers. Up-regulation of PTCH and GLI-I protein was demonstrated in both BCCs and OKs. The pattern of PTCH expression matched the PTCH transcript p attern previously reported in BCCs and appeared sufficiently characteristic in OKs to allow differentiation between syndromic and non-syndromic cysts. Copyright (C) 2001 John Wiley & Sons, Ltd.