Low RhoA expression is associated with adverse outcome in melanoma patients: a clinicopathological analysis

RhoA GTPase is physiologically involved in the formation of stress fibers, cellular contractility and polarity, maintenance of cell cycle and transcriptional control. During tumorigenesis, it plays roles in cancer cell proliferation, apoptosis, adhesion, invasion and metastasis. While RhoA seems to act as a tumor promotor in most malignancies, data regarding its function in skin melanoma are fragmentary and conflicting. We aimed to clarify the clinical significance of RhoA expression in melanoma by immunohistochemical evaluation of 134 primary tumors and subsequent statistical analysis with clinicopathological profiles of patients. Increased RhoA expression was associated with thinner tumors, higher grade of tumor-infiltrating lymphocytes and lack of disease recurrence. Moreover, we observed a trend towards higher RhoA expression in cases without concurrent metastases. Recurrence-free survival and melanoma-specific survival of patients with high RhoA-expressing tumors were significantly prolonged. Multivariable regression model adjusting for melanoma thickness and status of regional lymph nodes confirmed independent prognostic value of RhoA immunoreactivity. In summary, we found associations between RhoA expression and histopathological phenotype of primary tumors as well as patient survival which suggest a suppressive role of RhoA in skin melanoma.