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 follow-up in Wilms tumour (WT). Tissue polypeptide-specific antigen (TPS), a cytokeratin 18 proteolytic fragment, has been suggested to be of value in the clinical management of WT patients. Cytokeratin 18 fragments are an early indicator of apoptosis and cytokeratin 18 might influence tumour cell behaviour. We investigated TPS expression in specimens of WT and other paediatric renal malignancies


METHODS
Immunoreactivity of WT sections (n = 9), clear cell sarcomas (CCSK, n = 3), and a renal cell carcinoma (RCC), and two pediatric kidney tumour cell lines (WT: SK-NEP-1 and rhabdoid tumour of the kidney: G-401) were investigated using the monoclonal antibody M3. Additionally, immunoblotting and RT-PCR analysis were performed. Cell culture supernatants were evaluated for TPS release. Serum TPS was measured in five patients at diagnosis, during chemotherapy and after surgical resection.


RESULTS
Moderate to strong immunoreactivity for TPS was found in tubular and blastemal components of nearly all (8/9) WT specimens. This was confirmed by Western-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 showed a time- and cell number-dependent increase of TPS release. Interestingly, TPS synthesis was demonstrated in SK-NEP-1 cells. Median preoperative serum TPS was elevated (293 U/l) compared to healthy children and lowest after surgical resection (49.5 U/l).


CONCLUSIONS
This is the first study demonstrating the synthesis and release of TPS by WTs and other paediatric renal malignancies. Considering the elevated levels of TPS in serum of these patients, a further investigation of this marker by larger clinical trials seems to be justified.
Rebhandl
W
W
Department of Paediatric Surgery, University of Vienna Medical School, Währinger Gürtel 18-20, A-1097 Vienna, Austria. winfried.rebhandl@akh-wien.ac.at
Handisurya
A
A
Memaran
N
N
Felberbauer
F X
FX
Aberle
J
J
Paya
K
K
Strobl
B
B
Horcher
E
E
D000293:Adolescent; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D015153:Blotting, Western; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007633:Keratins / Q000032:analysis / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000032:analysis*; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D009396:Wilms Tumor / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D010455:Peptides; D012333:RNA, Messenger; C089984:tissue polypeptide specific antigen; D007633:Keratins