Downregulation of transcription factor AP-2 predicts poor survival in stage I cutaneous malignant melanoma

Purpose: The transcription factor, activator protein (AP)-2, a 52-kd DNA-binding protein, is suggested to inhibit tumor growth through the activation of p21. To test this hypothesis, we analyzed AP-2 and p21 protein expressions in stage I cutaneous malignant melanomas to clarify their significance with regard to tumor progression and survival. Patients and Methods: A consecutive series of 369 clinical stage I cutaneous malignant melanoma patients were investigated using immunohistochemistry. The detected expression levels were correlated with each other, with clinicopathologic data, and with melanoma survival. Results: The loss of AP-2 expression was significantly associated with low p21 expression (P = .007), high tumor thickness (P = .001), high Clark's level (P = .046), high tumor-node-metastasis (TNM) category (P = .006), recurrent disease (P = .001), and male sex (P = .03). Tumor thickness, Clark's level, TNM category, bleeding, AP-2 index, and sex were all important predic tors of both recurrence-free survival (RFS) and overall survival (OS) of melanoma in this order. In Cox's multivariate analysis, high tumor thickness (P = .0001), low AP-2 index (P = .0153), and bleeding (P = .0143) predicted poor RFS. Poor OS was predicted by high tumor thickness (P = .0008) and bleeding (P = .0092). Conclusion: The loss of AP-2 expression seems to be associated with malignant transformation and tumor progression in cutaneous malignant melanoma. This tumor-suppressive action of AP-2 may be mediated through p21 regulation. Furthermore, decreased AP-2 expression is independently associated with elevated risk of subsequent metastatic behavior of stage I cutaneous malignant melanoma. (C) 1998 by American Society of Clinical Oncology.