The
retinoic acid-related orphan receptors (RORs) regulate several physiological and
pathological processes, including immune functions, development and
cancer. To study the potential role of RORs in
melanoma progression, we analysed RORα and RORγ expression in
nevi and primary
melanomas and non-lesional skin and
metastases in relation to
melanoma clinico-pathomorphological features. The expression of RORα and RORγ was lower in
melanomas than in
nevi and decreased during
melanoma progression, with lowest levels found in primary
melanomas at stages III and IV and in
melanoma metastases. Their expression correlated with pathomorphological pTNM parameters being low in aggressive
tumors and being high in
tumors showing histological markers of good prognosis. Higher nuclear levels of RORα and RORγ and of cytoplasmic RORγ correlated with significantly longer overall and disease free survival time. Highly pigmented
melanomas showed significantly lower level of nuclear RORs. This study shows that human
melanoma development and aggressiveness is associated with decreased expression of RORα and RORγ, suggesting that RORs could be important in
melanoma progression and host responses against the
tumor. Furthermore, it suggests that RORα and RORγ might constitute a novel druggable target in anti-
melanoma management using tumor suppressor gene
therapy restoring their normal functions.