Prognostic significance of RUNX3 expression in human melanoma

Abstract

RUNX3 is a tumor suppressor that plays important roles in cell proliferation, apoptosis, and metastasis. The authors investigated the role of RUNX3 in melanoma pathogenesis and analyzed the prognostic impact of RUNX3 expression in a large series of melanoma patients. Two sets of tissue microarrays were constructed, including 440 cases of melanomas (202 for the training set and 238 for the validation set) and 88 cases of nevi (25 normal nevi and 63 dysplastic nevi). RUNX3 expression was evaluated by immunohistochemistry. Positive RUNX3 expression was observed in 56%, 54%, 33%, and 24% of the biopsies in normal nevi, dysplastic nevi, primary melanoma, and melanoma metastases, respectively. Significant differences for positive nuclear RUNX3 staining were observed between dysplastic nevi and primary melanomas (P = .002, chi-square test), between dysplastic nevi and melanoma metastases (P < .001, chi-square test), and between primary melanoma and melanoma metastases (P = .045, chi-square test). Loss of RUNX3 expression was correlated with a worse 5-year survival of melanoma patients in both training and validation sets. Furthermore, loss of RUNX3 expression was also correlated with a poor 5-year disease-specific survival in primary melanoma (P = .001) and metastatic melanoma patients (P = .008). Multivariate Cox regression analysis revealed that positive RUNX3 expression is an independent prognostic factor to predict melanoma patient outcome. Our findings indicate that RUNX3 plays an important role in melanoma pathogenesis and may serve as a promising prognostic marker for melanoma.