Role of urinary cathepsin B and L in the detection of bladder urothelial cell carcinoma.

PURPOSE: We tested the hypothesis that urinary cathepsin B and L are associated with bladder cancer recurrence and invasiveness in patients with a history of nonmuscle invasive urothelial carcinoma of the bladder. MATERIALS AND METHODS: Cathepsin B and L, and NMP22 were determined in the urine specimens of 188 consecutive subjects with a history of treated urothelial carcinoma of the bladder, 31 with noncancerous urological conditions and 10 healthy subjects. Cathepsin B and L were analyzed as continuous and categorical variables based on their quartile distribution. RESULTS: Urinary cathepsin L was higher in the 122 patients with cystoscopic evidence of bladder tumor compared with levels in 107 with normal cystoscopy (median 5.9, IQR 4.4 vs 3.0, IQR 3.2, p <0.001). Higher levels of cathepsin L were associated with positive cytology assay results, higher NMP22 and T1 or greater pathological stage (each p <0.001). Area under the ROC curves of NMP22 and cathepsin L for bladder cancer detection were 0.704 (95% CI 0.637-0.772) and 0.793 (95% CI 0.736-0.850), respectively. On multivariate analysis cathepsin L, NMP22 and cytology were associated with invasive pathological stage (OR 1.29, 2.42 and 2.76, respectively, p

Cathepsins B, H, and L activities in urine of patients with transitional cell carcinoma of the bladder.

OBJECTIVES: Cathepsin B, H, and L (CB, CH, CL) are lysosomal proteolytic enzymes that belong to the group of cysteine proteinases. The imbalance between proteinases and their inhibitors is believed to correlate with tumor progression and shortened patient survival. In transitional cell carcinoma (TCC) only limited data have been published. METHODS: Using spectrofluorometric assays, catalytic activities of CB, CH, and CL in urine were measured to evaluate the potential diagnostic and prognostic value for patients with TCC of the bladder. Second morning urine was collected and used for measurements. CB, CH, and CL activities were determined for groups of patients with superficial disease (Ta-1, n = 43) and muscle-invasive tumors (T2, n = 18; or greater than T2, n = 9), as well as for different tumor grades (G1, n = 12; G2, n = 26; and G3, n = 31). For comparison, 14 urine samples from patients with bladder inflammation and 43 samples from a control group were also included. RESULTS: Compared with the control group, patients with superficial Stage Ta-T1 disease and muscle-invasive Stage T2 or greater disease, as well as patients with G3 tumors, revealed significantly higher urinary CL activity. CB and CH did not show any tumor-related activity increase. CB was significantly lower in patients with nonrecurrent tumors. CONCLUSIONS: These results suggest that elevated levels of CL in urine might be indicative of a cellular proteolytic imbalance in TCC of the bladder and may have a prognostic and/or diagnostic value.

[The value of urine cystein proteinase and serum CA125 measurement in monitoring the treatment of malignant ovarian tumor].

Urine cystein proteinase (UCP) and serum CA125 were measured in 40 patients with malignant ovarian tumor (malignant group), 40 patients with benign ovarian tumor (benign group), and 40 normal control (normal group). 28 patients in the malignant group underwent UCP and CA125 measurement pre-operation, post-operation, and during three courses of chemotherapy. The enzyme activity of UCP in the malignant group was significantly higher than that in the benign and normal groups (P < 0.05 or 0.01). The values of UCP in patients with malignant tumor of stages II-IV were significantly higher compared with those of stages I-II (P < 0.01, 0.05). The activity of UCP was elevated pre-operation, post-operation, and was much higher on the seventh day postoperation. After the seventh day, UCP activity decreased gradually. Serum CA125 was also detected pre-operation, at 7.30 and 60 days post-operation. The levels of UCP and CA125 pre-operation and 30, 60 days post-operation in the patients whose residual carcinoma lesions were > 2 cm in diameter were apparantly higher than those with no residual lesions (P < 0.05). UCP and CA125 values were measured in six patients before relaparotomy. The sensitivity, specificity, accuaracy, positive predictive value and negative predictive value for UCP assay are 980%, 100%, 83%, 100% and 50% and those for CA125 assay are 40%, 100%, 80%, 100%, and 25%, respectively.

[The values of urine cysteine protein activity in the diagnosis of ovarian cancer].

The levels of urine cysteine protease (UCP) were detected in the urines of 70 gynecological cancers, 50 gynecological benign tumors and 50 normal women. The values of UCP assay of gynecological cancers were much higher than those of benign and normal samples (P < 0.01). Best cut off point for diagnosis of gynecological cancers was P95 and UCP cut off value was 0.24 pmol.min-1/L by using percentile and ROC curve. The sensitivity of UCP assay was 90%, specificity 80% and accuracy 86%. The sensitivity for ovarian cancers was 95%, but 77% and 85% for corpus and cervical cancers respectively. There were no differences between UCP and CA125 (sensitivity 85%, specificity 87%, accuracy 84%) in the diagnosis of ovarian cancers. In 7 cases of 8 cases of stage I ovarian cancers, UCP were abnormal. In 6 cases of the same group, CA125 were normal (< 35,000 U/L). So UCP may be better than CA125 in the diagnosis of early ovarian cancer. The sensitivity of lactate dehydrogenase (LDH) isoenzyme was 75% in ovarian cancer which was lower than UCP and CA125, but the specificity 85%. LDH isoenzyme still was one of important tumor markers for diagnosis. Combined assays with UCP, CA125 and LDH isoenzyme may reach the sensitivity 96% and specificity 100% evidently. These data implied that UCP may be a good tumor marker in gynecological cancers especially for ovarian cancers in future.

Decrease in vivo of cysteine endopeptidases in blood of patients with tumor of the larynx.

Since cysteine endopeptidase (cathepsins B and L) have been proposed to be implicated in tumor malignancy, we have attempted to decrease these in vivo. Large amounts of urine cysteine peptidase inhibitors (UCPI) are present in the urine of patients. Our results indicate protective effects of a UCIP preparation against human serum cysteine endopeptidases.

[Assay of urine cysteine proteinase in diagnosing gynecological malignant tumors].

Cysteine proteinases (CP) belong to the subclass of endopeptidase, and have been considered to play an important role in spreading cancer cells. Cysteine proteinases in urine (UCP) were determined in 71 healthy women, 76 patients with gynecological benign tumors and 125 cases (173 samples) with gynecological malignant tumors. Enzyme levels were assayed using the artificial substrate CSZ-Ala-Arg-AFC by detecting the release of free AFC with the aid of a fluorometer. The value ranged from upper 80% to 99% of UCP in 71 normal women and was calculated with the percentile method. The results showed that ROC curve displayed a highly sensitive character. The sensitivity and specificity for gynecological malignant tumor were 91.8%, and 71.7% respectively. The sensitivities of UCP for ovarian cancer, cervical cancer, carcinoma of endometrium and cancer of vulva were 96%, 91%, 85.7% and 72.7% respectively. Due to its high sensitivity. It was suggested that UCP assay can be a good screening test to distinguish gynecological malignancy from benign tumors. The accuracy of diagnosing gynecological malignancy may be improved if UCP assay is combined with other tests with higher specificity.