Diagnostic value of tissue polypeptide-specific antigen (TPS) in neuroblastoma and Wilms' tumour

Abstract

Summary Although tissue polypeptide-specific antigen (TPS) has been described as a potentially useful serum marker of tumour activity in adult epithelial tumours, few data are available for childhood malignancies. Neuroblastomas and Wilms' tumours are the commonest types of solid malignancies found in the retroperitoneum of children. At The assay for tissue polypeptide-specific antigen (TPS) detects soluble fragments of cytokeratin 18 (Rydlander et al, 1996), an acid cytokeratin protein present in epithelial cells. Serum levels of TPS can be measured with an enzyme-linked immunosorbent assay (ELISA) that uses a high-affinity monoclonal antibody against M3, one of 35 identified epitopes of the tissue polypeptide antigen (TPA), which constitutes the specificity related to cell proliferation (Einarsson et al, 1997). TPS, as evaluated in cell culture supernatants, has been found to correlate with cell number and DNA synthesis rate (Madersbacher et al, 1993).Extensive studies have shown that TPS is useful in diagnosing and monitoring adult epithelial tumours of the breast (Einarsson, 1995;Bremer et al, 1996;Giai et al, 1996), lung (Pujol et al, 1994), prostate (Kramer et al, 1997) and gastrointestinal tract (Kornek et al, 1995). We have recently established normal values for paediatric patients (Rebhandl et al, 1997a), but few data are available as yet about TPS in paediatric malignancies. After cerebral malignancies, neuroblastoma and Wilms' tumour are the commonest solid tumours in childhood. They typically present as an upper abdominal mass.The aim of this study was to ascertain the role of TPS as a tumour marker for neuroblastoma and Wilms' tumour and determine its capability to discriminate between these two entities, as well as between benign and malignant tumours in general. (Rebhandl et al, 1997b); these samples were, therefore, excluded.We included 23 neuroblastomas (ten boys, 13 girls; mean age 2.2 years; range 2 weeks to 10.8 years), nine Wilms' tumours (four boys, five girls; mean age 3.7 years; range 7 weeks to 6.8 years) and 22 benign tumours (11 boys, 11 girls; mean age 2.3 years; range 2 weeks to 7.9 years) in the study.

Release of cytokeratin‐18 and ‐19 fragments (TPS and CYFRA 21‐1) into the extracellular space during apoptosis

“…In numerous clinical laboratories, levels of TPS and CYFRA 21-1 in the sera of cancer patients have been determined as an indirect measure of tumor progression [Nisman et al, 1998;Rebhandl et al, 1998;Tempfer et al, 1998;Nagler et al, 1999;Doweck et al, 2000], although the utility of this approach has been challenged for some tumor types [Plebani et al, 1993;Wollenberg et al, 1996;Theyer et al, 1999;Valik and Nekulova, 2000]. Since the release of TPS and CYFRA 21-1 can correlate with apoptosis in vitro, further studies are warranted to determine whether apoptotic epithelial cells can be a significant source of extracellular, soluble cytokeratins in vivo.…”

“…Serum concentrations of TPS and CYFRA 21-1 correlate with disease progression in various malignancies and thus have been used as tumor markers [Nisman et al, 1998;Rebhandl et al, 1998;Tempfer et al, 1998;Nagler et al, 1999;Doweck et al, 2000]. TPS and CYFRA 21-1 have traditionally been considered as proliferation markers, although the evidence for this association is limited, and the biology behind the release of soluble cytokeratin fragments actually remains poorly understood.…”

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

“…TPS appears in proliferating cells [24,25] and consequently constitutes one of the clinically relevant tumour activity markers in various adult epithelial tumours [26±29]. In WT, marker levels seem to correlate with therapeutic measures, thus offering a new diagnostic tool for therapy control and follow-up [2]. To assure the results reported for serum TPS measurements in WT patients [2], we studied the TPS expression in tumour specimens using the MoAb-M3.…”

“…We recently reported that tissue polypeptide-speci®c antigen (TPS), a cytokeratin 18 (K18)-derived tumour marker, is elevated in the serum of WT patients [2].…”

Saga of Wilms′ tumor: Lessons learnt from the past

“…[12] Hypertension may be associated with Wilms' tumor. In creased plasma prorenin and renin levels, found by sev eral investigators, could be the cause.…”