p53 mutation in nonmelanoma skin cancers occurring in psoralen ultraviolet a-treated patients: evidence for heterogeneity and field cancerization.
p53 mutation in nonmelanoma skin cancers occurring in psoralen ultraviolet a-treated patients: evidence for heterogeneity and field cancerization.
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DOI：
10.1046/j.1523-1747.2002.01814.x
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发表时间：
2002-08
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影响因子：
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通讯作者：
R. Stern;Svetlana V. Bolshakov;A. Nataraj;H. Ananthaswamy
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文献类型：
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作者：
R. Stern;Svetlana V. Bolshakov;A. Nataraj;H. Ananthaswamy
牛皮癣和紫外线A辐射的组合被广泛用于治疗牛皮癣。长期、高剂量暴露于补骨脂素+紫外线A与非黑色素瘤皮肤癌，特别是鳞状细胞癌的风险增加有关。在这项研究中，我们使用p53突变作为分子标记，以确定单独的贡献，p53+紫外线A和其他紫外线暴露，如紫外线B的皮肤癌的发展，p53+紫外线A治疗银屑病患者。结果表明，在分析的69个肿瘤中，37个（54%）肿瘤有一个或多个p53突变。在37个突变的肿瘤中，17个（46%）肿瘤仅具有紫外线型突变，2个（5%）肿瘤仅具有peptide+紫外线A型突变，18个（49%）肿瘤具有两种类型的突变。有趣的是，在高剂量暴露于紫杉醇+紫外线A的患者中，紫杉醇+紫外线A型p53突变比紫外线型更常见。在同一患者甚至同一肿瘤中，常出现实地癌变和肿瘤异质性。这项研究的数据表明，p53基因突变可能在p53+紫外线A治疗患者的非黑色素瘤皮肤癌的发展中发挥重要作用，但这些突变可能与其他致癌暴露，特别是紫外线B，在皮肤癌的发展中的作用一致。
A combination of psoralens and ultraviolet A radiation is widely used to treat psoriasis. Long-term, high-dose exposure to psoralen + ultraviolet A is associated with an increased risk of nonmelanoma skin cancer, particularly squamous cell carcinoma. In this study, we used p53 mutations as a molecular marker to determine the separate contributions of psoralen + ultraviolet A and other ultraviolet exposures, such as ultraviolet B for skin cancer development in psoralen + ultraviolet A-treated psoriasis patients. The results indicated that of 69 tumors analyzed, 37 (54%) tumors had one or more p53 mutations. Of 37 tumors with mutations, 17 (46%) tumors had only ultraviolet-type mutations, two (5%) tumors had only psoralen + ultraviolet A-type mutations, and 18 (49%) tumors had both types of mutations. Interestingly, psoralen + ultraviolet A-type p53 mutations were more frequent than ultraviolet type in tumors arising in patients with high-dose exposure to psoralen + ultraviolet A. Field cancerization and tumor heterogeneity appeared to occur frequently in the same patient and even in the same tumor. This study's data suggest that psoralen + ultraviolet A-induced p53 mutations may play an important part in the development of nonmelanoma skin cancer in psoralen + ultraviolet A-treated patients, but these mutations are likely to act in concert with the effects of other carcinogenic exposures, particularly ultraviolet B, in the development of skin cancer.