The molecular signature for urothelial carcinoma of the upper urinary tract.
OBJECTIVE
Frequent loss of heterozygosity of microsatellites on a specific chromosomal region has been reported in various types of human cancer. The same loss of heterozygosity has also been identified in matched serum or urine DNA. We determined a urine microsatellite marker profile specific to urothelial carcinoma of the upper urinary tract.


METHODS
We analyzed the loss of heterozygosity of primary tumors and their matched urine DNA samples from 30 patients with urothelial carcinoma of the upper urinary tract. We investigated a total of 77 markers from 25 chromosomal regions and a total of 53 from 23 chromosomal regions for their preferential loss in urothelial carcinoma and renal cell carcinoma of the kidney, respectively. Specificity was then confirmed in a cohort of 22 renal cell carcinoma cases.


RESULTS
Of 30 patients with urothelial carcinoma 25 (83.3%) were detected using the molecular urine test. Of 48 markers detected as loss of heterozygosity in urine 20 (41.7%) were localized at the chromosomal loci reported for renal cell carcinoma. The diagnostic specificity of the remaining 31 markers was cross-validated in a renal cell carcinoma cohort. With the cutoff set at 100% specificity urothelial carcinoma was accurately diagnosed in 24 of 30 patients (80.0%) using 13 markers, including D9S195, D18S67, GSN, D1S162, D8S261, D3S1300, D21S1436, D16S310, D3S1307, FABP2, D11S907, D15S1007 and D13S133.


CONCLUSIONS
The marker panel may permit a high throughput differential diagnosis of urothelial carcinoma of the upper urinary tract from that of renal cell carcinoma at an early stage of disease. The accurate diagnosis of renal cancer may help determine appropriate treatment planning and minimizing intraoperative frozen consultation.
Ho
Chung-Liang
CL
Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China.
Tzai
Tzong-Shin
TS
Chen
Jung-Chin
JC
Tsai
Hung-Wen
HW
Cheng
Hong-Lin
HL
Eisenberger
Claus F
CF
Chow
Nan-Haw
NH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007682:Kidney Pelvis; D019656:Loss of Heterozygosity; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010865:Pilot Projects; D014513:Ureter; D016482:Urinalysis; D014571:Urologic Neoplasms / Q000175:diagnosis / Q000235:genetics*; D019459:Urothelium