Detection of bladder carcinoma by combined testing of urine for hyaluronidase and cytokeratin 20 RNAs.
BACKGROUND
A new, sensitive, noninvasive method for the detection of urothelial carcinomas of the urinary bladder would open new possibilities in both the diagnosis and followup of patients.


METHODS
This study included 228 patients diagnosed with bladder carcinoma, 68 patients with benign bladder lesions, and 44 healthy persons served as the control group. All were subjected to: serologic schistosomiasis antibody assay in serum, urine cytology, estimation of urine hyaluronic acid (HA) by enzyme-linked immunosorbent assay, and detection of CK-20 and hyaluronidase (HAase) by reverse transcription polymerase chain reaction (RT-PCR) in urothelial cells from voided urine.


RESULTS
HA mean rank was higher in benign and malignant groups than in the healthy group (P < 0.0001) and was significantly related to tumor grade (P = 0.021). HA best-cutoff, determined using receiver operating characteristic curve to discriminate between malignant and nonmalignant groups, was 58.5 units/mg protein at 85.8% sensitivity and 60.7% specificity. HAase RNA showed superior sensitivity (90.8%) over cytology (68.9%) and CK-20 (78.1%) with specificity of 93.4%, 98.1% and 80.2%, respectively. The sensitivity reached 94.7% at a specificity of 91.5% when combined with CK-20. All 4 of the investigated markers were related to grade at P <0.05. Whereas only HAase and CK-20 were significantly related to stage (P < 0.05). As to schistosomiasis, only HAase RNA positivity was significantly associated (P = 0.038).


CONCLUSIONS
HAase RNA is a promising noninvasive test with high sensitivity and specificity in bladder carcinoma detection.
Eissa
Sanaa
S
Oncology Diagnostic Unit, Medical Biochemistry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. sanaa_eissa@ems.org.eg
Kassim
Samar K
SK
Labib
Randa Ali
RA
El-Khouly
Inas M
IM
Ghaffer
Taghreed M
TM
Sadek
Mohamed
M
Razek
Omar Abdel
OA
El-Ahmady
Omar
O
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000652:urine*; D007381:Intermediate Filament Proteins / Q000652:urine*; D053554:Keratin-20; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012313:RNA / Q000652:urine; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000652:urine*
D014408:Biomarkers, Tumor; D007381:Intermediate Filament Proteins; C507499:KRT20 protein, human; D053554:Keratin-20; D012313:RNA; D006821:Hyaluronoglucosaminidase