Corticotropin-Releasing Hormone in Melanoma and Nonmelanoma Skin Cancer

Background: Corticotropin-releasing hormone (CRH) regulates immunological and cellular processes. Recently, CRH is expressed in skin cancers, where its expression appears to correlate with the degree of malignancy. Objective: This study correlates CRH expression in melanoma metastases with patient survival and compares the intensity of CRH expression in melanoma to that in less aggressive skin cancer entities. Methods: Tissue microarrays with cores from 94 melanomas and 40 melanocytic nevi and 51 slides from 41 basal cell carcinomas (BCCs) and 10 squamous cell carcinomas (SCCs) were immunohistochemically stained for CRH. The intensity of CRH expression in melanoma metastases was stratified by sex and correlated with patient survival. Furthermore, proliferation and apoptosis were assessed in CRH-stimulated A431 cells using enzyme-linked immunosorbent assays and an apoptosis detection kit. Results: The intensity of CRH expression was higher in primary melanomas than in melanocytic nevi. Higher CRH expression was also found in melanoma metastases from women compared to men. However, higher CRH expression was correlated with reduced overall survival only in men. Compared to melanoma, BCCs and SCCs showed weaker CRH expression, which was in line with the finding that in vitro, CRH stimulation of the A431 cells reduced their proliferative activity. Conclusion: CRH does not necessarily correlate with the degree of malignancy, as semimalignant cancers such as BCC show higher levels of CRH expression than SCCs. In melanoma, CRH expression in metastases may be an important prognostic factor for overall survival in men, which needs further evaluation.