The effect of the sun on expression of β-catenin, p16 and cyclin d1 proteins in melanocytic lesions
The effect of the sun on expression of β-catenin, p16 and cyclin d1 proteins in melanocytic lesions
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DOI：
10.1111/j.1365-2230.2007.02507.x
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发表时间：
2007-11-01
影响因子：
4.1
通讯作者：
Delmas, V.
中科院分区：
文献类型：
--
作者：
Demirkan, N. C.;Kesen, Z.;Delmas, V.
背景肿瘤抑制基因产物p16在黑色素瘤恶性进展过程中经常失活。尽管p16在黑色素瘤中的重要性已被充分证明，但其与细胞周期蛋白D1、β-连环蛋白和紫外线辐射（UVR）的关系仍不清楚。目的：确定这些细胞周期相关蛋白和高危日光暴露在黑色素细胞病变生物学行为中的作用。方法：我们用免疫组织化学方法检测了28例黑色素细胞痣，其中28例为黑色素细胞痣。（MN; 9种先天性和19种获得性类型）和24种原发性皮肤恶性黑色素瘤（CMM; 19种结节性黑色素瘤，3种恶性雀斑样黑色素瘤，1种肢端雀斑样黑色素瘤和1种浅表扩散性黑色素瘤）的p16、细胞周期蛋白D1和β-连环蛋白的存在。黑色素细胞病变被分为两组，以检查紫外线对这三种蛋白质的影响：高风险的阳光照射（慢性阳光损伤; CSD），或低风险的阳光照射（非慢性阳光损伤;非CSD）。我们评估了这些蛋白质的产生与病变的组织病理学和临床特征之间的关系。p16蛋白的表达在多数CMM中受到抑制，但在MN中没有受到抑制（P < 0.0001）。细胞周期蛋白D1在CMM中过量产生，但在MN中没有，β-连环蛋白在MN和CMM中经常过量产生。β-catenin的过度表达在CSD黑素细胞病变中并不常见，但在非CSD黑素细胞病变中更常见（P = 0.027）。一个免疫组化面板，包括黑素细胞标志物富集p16和细胞周期蛋白D1可以用来区分一些边界黑素细胞病变。此外，Wnt/β-连环蛋白通路在非CSD中比在CSD黑素细胞病变中更频繁地被激活。
Background. The tumour suppressor gene product, p16, is often inactivated during melanoma malignant progression. Although the importance of p16 in melanomas is well documented, its relationship with cyclin D1, beta-catenin and ultraviolet radiation (UVR) remains unclear.Aim.To determine the role of these cell cycle-related proteins and high-risk sun exposure in the biological behaviour of melanocytic lesions.Methods.We used immunohistochemistry to examine 28 melanocytic naevi (MN; 9 congenital and 19 acquired types) and 24 primary cutaneous malignant melanomas (CMM; 19 nodular melanomas, 3 lentigo maligna melanomas, 1 acral lentiginous melanoma and 1 superficial spreading melanoma) for the presence of p16, cyclin D1 and beta-catenin. The melanocytic lesions were classified into two groups to examine the effects of UVR on these three proteins: high risk of sun exposure (chronically sun damaged; CSD), or low risk of sun exposure (nonchronically sun damaged; non-CSD). We evaluated the relationship between the production of these proteins and the histopathological and clinical characteristics of the lesions.Results. Production of p16 was repressed in most CMM, but not in MN (P < 0.0001). Cyclin D1 was overproduced in CMM but not in MN, and beta-catenin was frequently overproduced both in MN and CMM. Overproduction of beta-catenin was not common in CSD melanocytic lesions, but was more frequent in non-CSD melanocytic lesions (P = 0.027).Conclusion. An immunohistochemical panel including melanocytic markers enriched by p16 and cyclin D1 could be used to differentiate some borderline melanocytic lesions. In addition, the Wnt/beta-catenin pathway was more frequently activated in non-CSD than in CSD melanocytic lesions.