Noninvasive Transitional Cell Carcinoma Research Articles

Inhibitory effect of partial cystectomy on experimental carcinogenesis in the urinary bladder.

It was our aim in the present animal experiments to study the influence of stimulation of proliferative activity on carcinogenesis in the urinary bladder. Stimulation of urothelial proliferation was achieved by a one-third resection of the bladder. N-butyl-N-(4-hydroxybutyl)- nitrosamine (BBN), which was used as a carcinogen, was administered by gavage in three fractionated doses when proliferative activity was highest at 30, 45, and 70 h postoperatively. Contrary to our working hypothesis, the incidence of urinary bladder tumors proved to be significantly reduced by partial cystectomy. After administration of a low total dose of BBN (300 mg/kg bodyweight) and an experimental period of 6, 12, and 18 months, only 2.6% of the rats with a partial cystectomy, but 12.6% of the control animals with an intact bladder had developed papillomas and noninvasive papillary transitional cell carcinomas. Following administration of BBN at a higher total dose (1,300 mg/kg bodyweight), bladder tumors occurred after an induction period of 4, 6, and 12 months in 27.4% of the partially cystectomized and 48.1% of the nonoperated rats. Multiple tumors were found more frequently in the controls than in the operated animals. The reduction in the tumor incidence following one-third resection of the bladder evidently does not depend on a prolongation of the latency period or induction time. From findings in analogous experimental models it is conceivable that the observed inhibition of experimental bladder carcinogenesis is brought about by an increased capacity of the proliferating urothelial cells to repair carcinogen-induced DNA damage. Further studies are required to elucidate the significance of a stimulated proliferation for the repair system and neoplastic transformation of the urothelium.

Use of monoclonal antibodies for the localization of tissue isoantigens A and B in transitional cell carcinoma of the upper urinary tract.

Employing the indirect immunoperoxidase technique, monoclonal antisera against blood group antigens A and B were used to localize the corresponding tissue isoantigens in normal ureter and transitional cell carcinoma of the ureter and renal pelvis in 29 patients. All five cases of normal ureters showed positive staining of tissue isoantigens within the transitional epithelium, and all twelve cases of noninvasive transitional cell carcinoma showed similar staining in tumor cells. Of the remaining twelve cases who had invasive tumor, eight lacked tissue isoantigens, while four cases exhibited positive staining. These results support the earlier findings that normal urothelium and noninvasive transitional cell carcinoma of the urinary tract possess ABO tissue isoantigens, while these isoantigens are most frequently absent in invasive tumors. In addition, this study also demonstrates that invasive transitional cell carcinoma of ureters and renal pelvis may continue to possess tissue isoantigens when studied by this sensitive, specific method.

A, B, O (H) antigenic determinants in superficial transitional cell tumors of bladder

The initial tumors of 21 patients who earlier had presented with superficial noninvasive transitional cell carcinoma of the bladder and who subsequently underwent cystectomy for invasive disease were examined by the specific red cell adherence test. Eighteen of 21 initial tumors (85.7%) were antigen negative. The time from initial tumor resection ranged from twelve to 168 months (mean thirty-eight months). Loss of blood group antigens indicated enhanced biologic aggressiveness of tumors. However the interval to invasion is sufficiently variable as to preclude the use of this assay for timing of radical cystectomy.

Titration of natural and disease-related cytotoxicity of lymphocytes from bladder cancer patients

A controlled investigation of lymphocyte-mediated cytotoxicity has been carried out in patients with transitional cell carcinoma (TCC) of the urinary bladder, three long-term established cell lines with comparable sensitivities to the natural cytotoxicity (NC) being used as targets, namely HU 456 derived from human TCC, HU 609 from normal human urothelium, and SAOS 2 from a human osteosarcoma. The 44-h incubation microcytotoxicity assay (MA) was used with ‘blinded’ semiautomatic visual counting of target cells. The cytotoxicity was determined by titration with a serial dilution of lymphocyte suspensions 1:2, five different concentrations being used in each experiment. Fifty tests were performed with lymphocytes from 48 TCC patients. As controls, 65 patients with diseases other than TCC were tested simultaneously. The average cytotoxicity of lymphocytes from TCC patients against HU 456 was only slightly and insignificantly higher than that of the control patients. However, a marked decrease of the NC against the control cells HU 609 and SAOS 2 was noted with TCC patient lymphocytes. After correction of the data for the depression of background NC, increased tumor-specific cytotoxicity (TSC) and tumor type-specific cytotoxicity (TTSC) were demonstrated in TCC patients with noninvasive malignant tumors (grade 2 or 3), whereas no increased specific cytotoxicity was found in TCC patients with invasive grade 2 or 3 tumors. Neither was any increased specific cytotoxicity found in patients with very well-differentiated grade tumors. The presence of specific reactivity in patients with noninvasive TCC in contrast to invasive TCC is supposed to indicate growth-controlling function of the cellular immune reaction. Tests were also performed with lymphocytes from 35 patients in the postoperative phase without any history of TCC. Surprisingly, this group revealed a significantly elevated TSC but not increased TTSC when compared with the 65 untreated control patients, thus indicating that serious reservations must be made in the interpretation of the cytotoxocity assay.

The Prognostic Value of Cell Surface Antigens in Low Grade, Non-Invasive, Transitional Cell Carcinoma of the Bladder

Tumors in 23 patients who presented with a low grade, non-invasive transitional cell carcinoma of the bladder were studied for blood group antigens A, B or O on the cell surface. Of 14 patients without cell surface antigens initially 13 suffered an invasive tumor subsequently and 1 had diffuse carcinoma in situ. Of 9 patients with cell surface antigens initially 8 did not have an invasive recurrence during a 5 or more-year followup and 1 did. The presence or absence of blood group cell surface antigen on a low grade, non-invasive transitional cell carcinoma of the bladder would seem to have value in predicting future recurrence with muscle invasion.