Expression of cytokeratin-18-related tissue polypeptide-specific (TPS) antigen in Wilms tumor

Background. So far, there is no approved tumour marker for diagnosis or fol low-up in Wilms tumour (WT). Tissue polypeptide-specific antigen (TPS), a c ytokeratin 18 proteolytic fragment, has been suggested to be of value in th e clinical management of WT patients. Cytokeratin 18 fragments are an early indicator of apoptosis and cytokeratin 18 might influence tumour cell beha viour. We investigated TPS expression in specimens of WT and other paediatr ic renal malignancies. Procedure. Immunoreactivity of WT sections (n=9), cl ear cell sarcomas (CCSK, n=3), and a renal cell carcinoma (RCC), and two pe diatric kidney tumour cell lines (WT: SK-NEP-1 and rhabdoid tumour of the k idney: G-401) were investigated using the monoclonal antibody M3. Additiona lly, immunoblotting and RT-PCR analysis were performed. Cell culture supern atants were evaluated for TPS release. Serum TPS was measured in five patie nts at diagnosis, during chemotherapy and after surgical resection. Results . Moderate to strong immunoreactivity for TPS was found in tubular and blas temal components of nearly all (8/9) WT specimens. This was confirmed by We stern-blotting. Cystic and epithelial-like portions of CCSKs and RCC showed distinct reactivity (3/3). The supernatant of G-401 but not of SK-NEP-1 sh owed a time and cell number-dependent increase of TPS release. Interestingl y, TPS synthesis was demonstrated in SK-NEP-1 cells. Median preoperative se rum TPS was elevated (293 U/l) compared to healthy children and lowest afte r surgical resection (49.5 U/l). Conclusions. This is the first study demon strating the synthesis and release of TPS by WTs and other paediatric renal malignancies. Considering the elevated levels of TPS in serum of these pat ients, a further investigation of this marker by larger clinical trials see ms to be justified. Med Pediatr Oncol 2001;37:357-364. (C) 2001 Wiley-Liss, Inc.