Carbonic anhydrase IX as a diagnostic urinary marker for urothelial bladder cancer.

UNLABELLED: Urinary biomarkers are needed to improve the management and reduce the cost of urothelial bladder cancer (UBC); however, none have been recommended yet for clinical practice. This study evaluated carbonic anhydrase IX (CAIX) as a diagnostic urinary biomarker for UBC. CAIX was analyzed by quantitative polymerase chain reaction in urine samples of 196 patients with UBC and 123 controls with hematuria. Paired samples from urine and tumor tissue were evaluated in 16 cases. Data were validated in 155 independent samples. The sensitivity and specificity of CAIX for UBC detection were 86.2% and 95.1%, respectively (area under the curve [AUC]: 90.5%). There was a significant association of CAIX expression between the paired urine and tumor specimens (p=0.002). CAIX showed a significantly higher predictive accuracy than urinary cytology (90.5% vs 71.7%), specifically in low-grade tumors (90.0% vs 61.8%). CAIX expression decreased with increasing tumor stage and grade. Analyses in an independent validation cohort confirmed the high accuracy of CAIX for diagnosing UBC (AUC: 88.3%). PATIENT SUMMARY: We evaluated carbonic anhydrase IX (CAIX) as a urinary marker for bladder cancer (BCa) using a large series of patients from a single hospital. We found that urinary CAIX has a high sensitivity and specificity for diagnosing BCa.

Aurora A Kinase as a diagnostic urinary marker for urothelial bladder cancer.

OBJECTIVE: To evaluate urinary Aurora A Kinase (AURKA) mRNA expression as a diagnostic biomarker for urothelial bladder cancer (UBC). METHODS: One hundred and eighty-eight urine samples from patients with UBC (n = 122) and controls with hematuria (n = 66) were investigated. AURKA expression was quantified using real-time PCR and compared with voided urinary cytology. Associations with stage and grade were assessed. The area under curve was used to quantify the predictive accuracy (PA). RESULTS: The sensitivity and the specificity of AURKA for UBC were 83.6 and 65.2 %, respectively (PA = 74.4 %). Among those with detectable AURKA, the quantity of expression was similar in cases and controls. Compared with Ta, tumors staged T1 and T2 showed a 9.31-fold and 4.78-fold increased AURKA expression (p = 0.034), respectively. Further, high-grade tumors showed 5.33-fold higher expression levels than low-grade tumors (p = 0.031). AURKA and urinary cytology showed similar overall PA for UBC detection (74.4 vs. 72.1 %, p = 0.588). For low-grade tumors, AURKA was more accurate (72.5 vs. 59.0 %, p = 0.004), while cytology was more accurate for high-grade lesions (76.8 vs. 89.1 %, p = 0.011). CONCLUSIONS: In patients with hematuria, AURKA is associated with the presence and grade of UBC, suggesting a role as diagnostic and prognostic biomarker. As AURKA is more accurate in low-grade tumors but less accurate in high-grade tumors than urinary cytology, both could be complementary in detecting UBC.

The value of transurethral bladder biopsy after intravesical bacillus Calmette-Guérin instillation therapy for nonmuscle invasive bladder cancer: a retrospective, single center study and cumulative analysis of the literature.

PURPOSE: We evaluated the need of routine transurethral biopsies after an induction course of intravesical bacillus Calmette-Guérin for high grade nonmuscle invasive bladder cancer. MATERIALS AND METHODS: This retrospective study included 180 patients with high grade nonmuscle invasive bladder cancer who underwent a 6-week induction course of bacillus Calmette-Guérin. Cystoscopic findings, urinary cytology and pathological results of transurethral biopsy were evaluated. For cumulative meta-analysis we systematically reviewed studies indexed in MEDLINE®, EMBASE® and Web of Science®. The records of 740 patients from a total of 7 studies were finally analyzed. RESULTS: Biopsy was positive in 58 patients (32%). Cystoscopy appeared normal in 75 patients (42%) and showed only erythema in 51 (28%) and tumor in 54 (30%), of whom 6 (8%), 11 (22%) and 41 (76%), respectively, showed positive findings at biopsy. The positive predictive value of erythema was 15% with negative cytology and 56% with positive cytology. The positive predictive value of a tumor with negative and positive cytology was 63% and 89%, respectively. A combination of negative cytology and normal cystoscopy was associated with a negative biopsy in 94% of cases. A total of 970 bladder biopsies were taken, of which 137 (14%) were positive, including 20 of 125 erythematous lesions (16%), 73 of 107 tumors (68%) and 44 of 738 normal-appearing areas (6%). Cumulative analysis findings were comparable. CONCLUSIONS: Routine transurethral bladder biopsies after a bacillus Calmette-Guérin induction course are not necessary. An individually approach is recommended, tailored from cystoscopic findings and cytology.

DNA profiles and numeric histogram classifiers in nephrogenic adenoma.

BACKGROUND: The malignant potential of nephrogenic adenoma is still a matter of controversy and therapeutic regimens of this morphologic entity range from partial, even total cystectomy to watchful waiting. The objective of the current study was to evaluate several robust image cytometry-DNA histogram classifiers and to search among those for factors that separate a biologically nonaggressive metaplastic lesion from lesions with increased malignant potential. METHODS: The study included bladder irrigation specimens, 23 preceding transurethral resection of nephrogenic adenoma and 24 preceding resection of papillary bladder carcinoma. Feulgen-stained nuclei were imported to a static image analysis system, and densitometric data were interpreted by two different software programs. Histograms were described numerically by DNA index, 2c deviation index, and by 5c/9c-exceeding and euploid polyploidy rates. In addition, an interpretation algorithm based on a dual parameter analysis with an integrated automatic threshold was used. RESULTS: The numeric classification of DNA histograms of patients suffering from nephrogenic adenoma resulted in DNA indices between 0.91 and 1.15. The 2c deviation indices ranged from 0.03 to 0.43, and the 5c exceeding rates ranged from 0.0 to 1.58. None of the measurements showed nuclei exceeding 9c. The p25-75 ranges of 2c deviation indices in nephrogenic adenoma and papillary urothelial carcinoma did not overlap. These findings might be explained by minor proliferative activity in nephrogenic adenoma. Euploid polyploidy rates less than 5% confirm this explanation. Risk analysis documented high risk only for those patients with nephrogenic adenomas who had proven transitional cell carcinoma in their history. CONCLUSIONS: DNA estimation by image cytometry of urinary bladder irrigation specimens appears able to separate papillary bladder lesions. The method detects those lesions with higher malignant potential but is limited in separating entities with low malignant potential. Comparison of the discriminative power of robust numeric DNA classifiers reveals the 2c deviation index superior to the widely used DNA index and the 5c exceeding rate in this material.