Performance of nuclear matrix protein 22 urine marker and voided urine cytology in the detection of urinary bladder tumors.

BACKGROUND: Cystoscopy with urinary cytology is the gold standard for the diagnosis and follow-up of patients with tumors of the urinary bladder. The aim of the study was to evaluate the performance of the nuclear matrix protein 22 (NMP22) tumor marker test, BladderChek® point-of-care test and voided urinary cytology for the detection and follow-up of bladder tumors. METHODS: NMP22 was measured using an ELISA assay in stabilized voided urine and using the BladderChek® test. Voided urinary cytology was performed on urine samples. Results were compared to cystoscopic findings and histopathological examination results after transurethral resection of the bladder lesion. RESULTS: For the prediction of malignant histopathological result, sensitivity and specificity were 45.2% and 75.0%, respectively, for NMP22 at a cut-off of 7.5 kU/L, 17.7% and 100% for the BladderChek® test and 37.0% and 100% for voided urine cytology. For the prediction of suspicious or positive cystoscopic finding, sensitivity and specificity were 40.4% and 72.1%, respectively, for NMP22 at a cut-off of 7.5 kU/L, 14.8% and 93.8% for the BladderChek® test and 26.8% and 98.1% for voided urine cytology. CONCLUSIONS: The NMP22 quantitative test showed higher sensitivity and lower specificity compared with voided urine cytology, whereas the sensitivity of the BladderChek® test was low. We could not recommend any of the three non-invasive tests as a replacement for cystoscopy for the diagnosis or follow-up of urinary bladder tumors.

The presence of the CYP11A1 (TTTTA)6 allele increases the risk of biochemical relapse in organ confined and low-grade prostate cancer.

The involvement of the CYP11A1 gene in the synthesis of androgens makes it a compelling candidate for various hormone-dependent diseases, including prostate cancer. A microsatellite polymorphism (TTTTA)n in the promoter region of the CYP11A1 gene has been reported to be associated with an increased risk of metastatic and high-grade prostate cancer. In the present study of 110 prostate cancer patients and 96 population controls, we examined the association between the CYP11A1 (TTTTA)n polymorphism and prostate cancer risk, aggressiveness, and incidence of biochemical relapse after prostatectomy. We have also evaluated the potential of the (TTTTA)n polymorphism as a microsatellite marker for the detection of genomic instability in prostate cancer. A strong association of the genotype containing the (TTTTA)6 allele with the occurrence of biochemical relapse after prostatectomy in patients with organ confined prostate cancer (p<0.0001), as well as in patients with low-grade prostate cancer (p=0.002) or both (p<0.0003) was determined. The incidence of biochemical relapse in patients with organ confined and low-grade prostate cancer in our study group was 22%, but increased to 50% in carriers of the (TTTTA)6 allele. Our findings also suggest (TTTTA)n instability as a potential marker for the detection of early events in carcinogenesis.

Mitochondrial localization of nitric oxide synthase in partially differentiated urothelial cells of urinary bladder lesions.

In urothelium, nitric oxide (NO) produced by NO synthase (NOS) plays various roles during disease processes. Because diseases influence the expression of uroplakins, the main urothelial differentiation-related proteins, we compared their expression and localization with that of inducible NOS (iNOS) in bladder outlet obstruction caused by benign prostatic hyperplasia and in noninvasive urothelial neoplasms (papilloma, low-grade, and high-grade papillary carcinoma). In all cases, we found areas with terminal and areas with partial cell differentiation. Terminally differentiated urothelium was uroplakin positive and iNOS negative. Areas of partial differentiation contained superficial cells with altered apical surface morphology and with no or weak uroplakin staining. These areas showed elevated iNOS staining. By immunoelectron microscopy, it was demonstrated for the first time that iNOS was localized in mitochondria of urothelial cells that show partial differentiation. These results suggest that various urinary bladder lesions alter the normal differentiation pathway of urothelial superficial cells, which induces the expression of NOS in mitochondria of partially differentiated cells.

Phase II study of radiochemotherapy with vinblastine in invasive bladder cancer.

Concurrent vinablastine-based radiochemotherapy was evaluated in 84 bladder-cancer patients. It was effective in more than half: tumour-specific survival (51% 9-year), local control rate (55% 9-year). The drawback was the impaired function of the bladder (9-year prevalence SOMA G3-4 symptoms: 66%), indicating the need for treatment aimed at reducing chronic morbidity.