Expression of c-Kit, p-ERK and cyclin D1 in malignant melanoma: An immunohistochemical study and analysis of prognostic value

Background: The mitogen-activated protein kinase (MAPK) signaling pathway is one of the major cascades that are crucial for the initiation and progression of melanoma; however, the influence of these signaling molecules on patient survival has not been clarified. Objective: The purpose of this study was to analyze the protein expression of MAPK signaling molecules in melanoma, and to correlate the expression status with clinicopathologic parameters. Methods: Expression of c-Kit, phosphorylated ERK (p-ERK), and cyclin D1 was examined by immunohistochemistry in 78 primary melanomas, 24 metastatic lesions, and in 42 benign nevi. The following clinicopathologic variables were evaluated: age, gender, histologic type, tumor site, Breslow thickness, Clark's level, ulceration, and survival period. Statistical analyses were performed for assessment of associations and melanoma-specific survival. Results: The expression of c-Kit, p-ERK, and cyclin D1 was significantly higher in primary melanomas than in nevi. c-Kit immunoreactivity was highest in thin (Tis-pT2) melanomas, and showed a significant reduction with tumor progression and metastasis. The expression of p-ERK was high in all stages of melanoma. Cyclin D1 positivity increased significantly according to tumor progression, but decreased in metastases. A significant correlation between p-ERK and cyclin D1 expression was observed. Survival analysis failed to detect any trends towards shorter or longer survival among patients expressing either c-Kit, p-ERK or cyclin D1. Conclusions: The expression of c-Kit, p-ERK, and cyclin D1 might help to differentiate thin melanoma from melanocytic nevus, but it appears to lack prognostic potential. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.