Human skin carcinoma arising from kidney transplant–derived tumor cells

Abstract

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.

Estimated Glomerular Filtration Rate and the Risk of Cancer

“…The observation that skin cancer risk (and particularly, nonmelanoma skin cancer risk) is elevated in persons with mild/moderate kidney disease is, however, novel. Although it expands earlier reports in patients undergoing kidney replacement therapy (35)(36)(37)(38)(39), possible mechanisms have not been fully elucidated. Nonmelanoma skin cancer in ESKD has been related to chronic inflammation, use of immunosuppressive medication, and uremic pruritus (36,39,40).…”

Assessment of Chimerism in Epithelial Cancers in Transplanted Patients

“…The possibility that these cancers might stem from mesenchymal stem cells that are coinfused with hematopoietic stem cells within the marrow transplant cannot be excluded. In a kidney transplant recipient, we were able to demonstrate the presence of the same p53-mutation in the tumor cells of a skin squamous cell carcinoma and in epithelial tubular cells in the kidney transplant in a biopsy performed 7 years before the occurrence of the skin squamous cell carcinoma [65] . To date, this is the only observation demonstrating the contribution of donor epithelium to the epithelial cancer in the recipient.…”

Donor-associated malignancy in kidney transplant patients

“…Immunosuppressive medications prevent the immune system from removing the mutant cancer cells, which -combined with the deleterious acterize DAM will help to understand the dynamic equilibrium between both normal and cancer stem cells and the skin microenvironment (7,15). These interactions could help explain why the p53 + renal tubule cells with the same TP53 mutation in the KTR described by Verneuil et al never formed a renal tumor (9).…”

“…For donor organ screening, current screening does not include genetic testing for cancer risk gene mutations. It is unclear whether the current report of DAM (9) should prompt a change in the screening approach. The likelihood of performing genetic testing on donor organs is remote at this point, due to the extremely low prevalence of DAM, the long turnaround time, the high cost associated with the genetic tests, and the ever-increasing clinical shortage of donor organs.…”

“…The majority of skin SCCs in KTRs originate from the recipient's skin epithelium, but donor cells from the transplanted kidney can also serve as a source. Verneuil et al (9) reviewed 21 skin SCCs from KTRs; in one patient, they identified a skin SCC with donor genotype, but not the recipient's. They confirmed that the microdissected p53 + cells in both recipient skin SCC and donor renal tubules had the same mitochondrial DNA-high-resolution melting patterns in all three markers, but were different from the recipient's DNA.…”