Enhanced expression of a tumor‐cell‐derived collagenase‐stimulatory factor in urothelial carcinoma: Its usefulness as a tumor marker for bladder cancers

A mouse monoclonal antibody (MAb) E11F4, previously raised against the tumor-cell-derived collagenase-stimulatory factor (TCSF) from LX-1 human lung-carcinoma cells, has been used to define the expression and distribution of TCSF in human non-neoplastic urothelium and tumors of the urinary bladder. Immunohistochemically, TCSF was detected in 27/28 transitional-cell carcinomas (TCC) of the bladder, of which 23 were judged to be positive for TCSF according to objective criteria. Twenty-four of 28 non-neoplastic urothelium from 22 individuals were judged to be negative for TCSF by this criteria. However, TCSF immunostaining that was confined to the superficial umbrella cells was frequently observed in non-neoplastic urothelium. In bladder carcinomas, TCSF was in most cases demonstrated in the majority of cells, including at the invasion front. Its localization to the cell membrane was demonstrated by immunoelectron microscopy. The high level of expression of TCSF in bladder tumors, but not in non-neoplastic urothelium, was also demonstrated by immunoblotting of tissue extracts. Furthermore, E11F4 immunostaining identified tumor cells obtained from bladder washings or voided urine and detected more TCC cases than conventional cytology. Since TCSF immunostaining was positive even in low-grade TCC (immunohistochemically and immunocytochemically in 4/5 TCC grade I), the application of TCSF immunostaining to urine cytology appears promising as a valuable adjunct to conventional methods in the clinical evaluation of patients with TCC.