Expression of c-Kit, p-ERK and cyclin D1 in malignant melanoma: An immunohistochemical study and analysis of prognostic value
Expression of c-Kit, p-ERK and cyclin D1 in malignant melanoma: An immunohistochemical study and analysis of prognostic value
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DOI：
10.1016/j.jdermsci.2011.02.011
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发表时间：
2011-05-01
影响因子：
4.6
通讯作者：
Furue, Masutaka
中科院分区：
文献类型：
--
作者：
Oba, Junna;Nakahara, Takeshi;Furue, Masutaka
背景：丝裂原激活蛋白激酶（MAPK）信号通路是对黑色素瘤的发生和进展至关重要的主要级联反应之一；目的：本研究的目的是分析黑色素瘤中MAPK信号分子的蛋白表达，并将表达状态与临床病理参数相关联。方法：采用免疫组化方法检测78例原发性黑色素瘤、24例转移性病变和42例良性黑色素瘤中c-Kit、磷酸化ERK（p-ERK）和细胞周期蛋白D1的表达。痣。评估以下临床病理变量：年龄、性别、组织学类型、肿瘤部位、Breslow 厚度、Clark 水平、溃疡和生存期。进行统计分析以评估关联性和黑色素瘤特异性生存。结果：原发性黑色素瘤中 c-Kit、p-ERK 和细胞周期蛋白 D1 的表达显着高于痣。 c-Kit 免疫反应性在薄型 (Tis-pT2) 黑色素瘤中最高，并且随着肿瘤进展和转移而显着降低。 p-ERK 在黑色素瘤的各个阶段均呈高表达。细胞周期蛋白 D1 阳性率随着肿瘤进展而显着增加，但在转移中下降。观察到 p-ERK 和细胞周期蛋白 D1 表达之间存在显着相关性。生存分析未能检测到表达 c-Kit、p-ERK 或细胞周期蛋白 D1 的患者存在任何缩短或延长生存的趋势。结论：c-Kit、p-ERK 和细胞周期蛋白 D1 的表达可能有助于区分薄黑色素瘤和黑素细胞痣，但似乎缺乏预后潜力。 (C) 2011 年日本皮肤病研究学会。由爱思唯尔爱尔兰有限公司出版。保留所有权利。
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.