Expression of proopiomelanocortin (POMC)-derived melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) peptides in skin of basal cell carcinoma patients

We proposed that local expression and production of proopiomelanocortin (PO MC) peptides may play a role in human skin physiology and pathology, includ ing the development and progression of skin cancers. Reverse transcription polymerase chain reaction (RT-PCR) and Northern blotting hybridization tech niques were used to study gene expression. Reversed-phase (RP) high-pressur e liquid chromatography (HPLC) separation with subsequent radioimmunoassays were used to identify alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) peptides. Immunocytochemistry (IHC) was used to localize ACTH, alpha-MSH, and beta-MSH antigens in skin. RT-PCR, R P-HPLC, and MC analyses documented the expression of POMC mRNA and producti on of ACTH and alpha-MSH peptides in lesional and perilesional skin of basa l cell carcinoma (BCC) patients and in cultured keratinocytes, which was ac companied by the expression of the MC1-R gene encoding the receptor activat ed by MSH and ACTH. Thirty specimens were analyzed by IHC. Immunoreactive a lpha-MSH, beta-MSH, and ACTH were detected, in 21 of 21, in 11 of 20, and i n 6 of 8 of lesional skin, and in 6 of 6, in 5 of 7, and in 6 of 8 perilesi onal skin specimens analyzed, respectively. Antigen distribution was hetero genous and present in BCC, epidermis, hair follicles, dermal mononuclear ce lls, and extracellular matrix. We conclude that messenger RNA for POMC, MC1 -R, and the peptides MSH and ACTH are produced in skin of BCC patients. Bec ause keratinocytes are a target for MSH and ACTH bioregulation, the product ion of these peptides is stimulated by UVB, and the peptides can act as imm unosupressors, we suggest that MSH and ACTH may facilitate development of B CC. Hmi PATHOL 30:208-215. Copyright (C) 1999 by W.B. Saunders Company.