Distinct Immunohistochemical Phenotype of Nonmelanoma Skin Cancers Between Renal Transplant and Immunocompetent Populations

Abstract

Nonmelanoma skin cancers (NMSCs), the most common malignancy in kidney transplant recipients (KTRs), are more frequent and aggressive in KTR than in the general population. These phenomena could be caused by immunosuppressive treatments, both by decreasing immunosurveillance and by a direct oncogenic potential. To assess the possible mechanisms involved in the clinical behavior of NMSC in KTR, we compared the tumoral expression of several molecule markers between 106 NMSC (basal cell carcinoma [BCC]; n=55, squamous cell carcinoma [SCC]; n=51) collected from 37 KTR and 51 control patients (CPs) from the general population. Immunohistochemical expression of transforming growth factor beta 1, epidermal growth factor receptor, protein 53 (p53), phospho-p70-S6-kinase, mammalian target of rapamycin (mTOR), and phospho-mTOR (Ser2448) were compared between KTR and CP and were also correlated with immunosuppressive therapy. p53 expression and transforming growth factor beta intensity were greater in SCC from KTR than from CP. In contrast, phospho-mTOR and phospho-p70S6K (Thr421Ser424) expressions were higher in SCC from CP. p53 and phospho-p70S6K (Thr389) expression were higher in BCC from KTR than from CP. Expression of the other biological markers showed no statistically significant differences between SCC and BCC from KTR treated with or without calcineurin inhibitors. Several prooncogenic markers showed distinct patterns of expression in NMSC from KTR. These differential characteristics could be responsible for the clinical behavior of posttransplantation NMSC. Furthermore, these markers may constitute possible targets for future therapeutic approaches to NMSC in KTR and could help to guide immunosuppressive therapy.