Čimbenici rizika za razvoj zloćudnih nemelanomskih tumora kože nakon transplantacije bubrega [Risk factors for development of non-melanoma skin cancer after renal transplantation]
Patients on immunosuppressive therapy are more prone to cancer development, with nonmelanoma skin cancers (NMSCs) being the most frequent ones.
The aim of the study was to examine the incidence of NMSCs the group of renal transplant recipients (RTR).
Risk factors for NMSC development were recorded, such as patients’ sex, age at transplantation, geographic background, duration of dialysis, type, intensity and duration of immunosuppression. In order to examine the role of Wnt4, the expression pattern was investigated in NMSCs of RTR and in a control group, a nontransplant group which is not under immunosuppressive therapy (77 paraffin embedded basal cell carcinomas (BCC) and 76 paraffin embedded squamous cell carcinomas (SCC)). Statistical significance was appointed to p<0,05.
The incidence of NMSC among RTRs was 6,81%., with basal cell carcinoma being the most prevalent one (BCC:SCC ratio 1,76:1). Males were more affected than females (P=0,007), with shorter mean interval between the time of transplantation and first cancer development (P=0,0001). Mean dialysis time before transplantation was 3 years (2–6 years), and mean time to first NMSC development was 5 years respectively. There was difference between age at transplantation; mean age at transplantation for patients transplanted before the year 2010 was 44 (32–53) and mean age at transplantation after 2010 was 53 (43–61) (P<0,0001). Time to first NMSC development is decreasing in later group. NMSC was observed in 5,3% of RTR who live along the Adriatic coast and in 7,3% of RTR who live in the continental part of Croatia; the difference is not statistically significant (P =0,241), nor is the time to first NMSC development between those two groups of patients (P=0,564). Patients receiving more intense therapy (which includes 3 immunosuppressive agents) did not develop more NMSC then patients receiving only 2 immunosuppressive agents (6,64% compared to 8,42 %) (P=0,556). There was significant difference in the incidence of NMSC between the groups of patients treated with different immunosuppressive agents; 3,1% of patients receiving tacrolimus developed NMSC which is significantly lower than 14,3% of NMSC among patients receiving cyclosporinA (P<0,0001). In addition, 5,9% of patients receiving mycophenolat mofetil and 15,8% of patients receiving azathioprine developed NMSC (P=0,001).
Immunohistochemical staining to Wnt4 antibody revealed cytoplasmic staining in NMSC cells and in the healthy tissue. Wnt4 staining was weaker in BCC and SCC when compared to the healthy skin (p<0,0001), pointing to influence of Wnt signaling in initial NMSC carcinogenesis. The difference between Wnt4 staining in RTR compared to control group indicates possible activation of different Wnt signaling pathways in carcinogenesis or coactivation of another Wnt ligands in the NMSC progression. However, the role of immunosuppression in Wnt4 expression and activation was not completely made clear.
Our results indicate RTRs as a high-risk group for NMSC development. Therefore, patients should undergo a dermatological skin examination prior to transplantation as well as regular dermatological follow up after transplantation considering the guidelines and risk factors for each individual patient
