Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina; Department of Medicine, Medical University of South Carolina, Charleston, South Carolina; Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina; Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.
J Am Acad Dermatol. 2014 Aug;71(2):359-65. doi: 10.1016/j.jaad.2014.02.039. Epub 2014 Apr 13.
Organ transplant recipients (OTRs) are at increased risk of developing nonmelanoma skin cancers. This has long been thought to be caused by immunosuppression and viral infection. However, skin cancer risk among individuals with AIDS or iatrogenic immunodeficiency does not approach the levels seen in OTRs, suggesting other factors play a critical role in oncogenesis. In clinical trials of OTRs, switching from calcineurin inhibitors to mammalian target of rapamycin inhibitors consistently led to a significant reduction in the risk of developing new skin cancers. New evidence suggests calcineurin inhibitors interfere with p53 signaling and nucleotide excision repair. These two pathways are associated with nonmelanoma skin cancer, and squamous cell carcinoma in particular. This finding may help explain the predominance of squamous cell carcinoma over basal cell carcinoma in this population. Mammalian target of rapamycin inhibitors do not appear to impact these pathways. Immunosuppression, viral infection, and impaired DNA repair and p53 signaling all interact in OTRs to create a phenotype of extreme risk for nonmelanoma skin cancer.
器官移植受者（OTR）发生非黑素瘤皮肤癌的风险增加。长期以来，人们一直认为这是由免疫抑制和病毒感染引起的。然而，艾滋病患者或医源性免疫缺陷个体的皮肤癌风险并未达到 OTR 所见的水平，这表明其他因素在肿瘤发生中起着关键作用。在 OTR 的临床试验中，从钙调神经磷酸酶抑制剂转换为雷帕霉素靶蛋白抑制剂可显著降低新发皮肤癌的风险。新的证据表明钙调神经磷酸酶抑制剂会干扰 p53 信号转导和核苷酸切除修复。这两条途径与非黑素瘤皮肤癌，特别是鳞状细胞癌有关。这一发现可能有助于解释该人群中鳞状细胞癌相对于基底细胞癌的优势。雷帕霉素靶蛋白抑制剂似乎不会影响这些途径。免疫抑制、病毒感染以及 DNA 修复和 p53 信号转导受损都会相互作用，使 OTR 产生非黑素瘤皮肤癌的极高风险表型。
