INSERM, U-728, Paris, France.
J Clin Invest. 2013 Sep;123(9):3797-801. doi: 10.1172/JCI66721. Epub 2013 Aug 27.
Tumor cells with donor genotype have been identified in human skin cancer after allogeneic transplantation; however, the donor contribution to the malignant epithelium has not been established. Kidney transplant recipients have an increased risk of invasive skin squamous cell carcinoma (SCC), which is associated with accumulation of the tumor suppressor p53 and TP53 mutations. In 21 skin SCCs from kidney transplant recipients, we systematically assessed p53 expression and donor/recipient origin in laser-microdissected p53+ tumor cells. In one patient, molecular analyses demonstrated that skin tumor cells had the donor genotype and harbored a TP53 mutation in codon 175. In a kidney graft biopsy performed 7 years before the skin SCC diagnosis, we found p53+ cells in the renal tubules. We identified the same TP53 mutation in these p53+ epithelial cells from the kidney transplant. These findings provide evidence for a donor epithelial cell contribution to the malignant skin epithelium in the recipient in the setting of allogeneic kidney transplantation. This finding has theoretical implications for cancer initiation and progression and clinical implications in the context of prolonged immunosuppression and longer survival of kidney transplant patients.
在同种异体移植后,已在人类皮肤癌中鉴定出具有供体基因型的肿瘤细胞;然而,供体对恶性上皮组织的贡献尚未确定。肾移植受者罹患侵袭性皮肤鳞状细胞癌(SCC)的风险增加,这与肿瘤抑制因子 p53 的积累和 TP53 突变有关。在 21 例肾移植受者的皮肤 SCC 中,我们系统地评估了激光显微切割的 p53+肿瘤细胞中的 p53 表达和供体/受体起源。在一名患者中,分子分析表明皮肤肿瘤细胞具有供体基因型,并在 175 密码子处携带 TP53 突变。在皮肤 SCC 诊断前 7 年进行的肾移植活检中,我们在肾小管中发现了 p53+细胞。我们在肾移植的这些 p53+上皮细胞中鉴定出相同的 TP53 突变。这些发现为同种异体肾移植中供体上皮细胞对受者恶性皮肤上皮组织的贡献提供了证据。这一发现具有癌症起始和进展的理论意义,并在长期免疫抑制和肾移植患者生存时间延长的背景下具有临床意义。