Prospective evaluation of the prognostic relevance of molecular staging for urothelial carcinoma.
BACKGROUND
Nearly 50% of urothelial carcinoma patients with lymph node-negative invasive cancers recur after radical surgery. In many cases, occult local or lymph node disease may be present but undetectable by current approaches. Reverse-transcriptase polymerase chain reaction (RT-PCR)-detectable mRNA of Uroplakin II (UPII), a urothelial-specific gene mRNA, was evaluated in perivesical and lymph node samples removed at radical surgery as a predictor of clinical recurrence.


METHODS
From November 1999 to August 2002, 46 patients with cTa-T4N0M0 urothelial bladder cancer enrolled in a prospective clinical trial and underwent radical cystectomy and pelvic lymphadenectomy. RT-PCR for UPII was performed on biopsies of the external surface of the bladder specimen and lymph nodes. Results were compared with conventional pathology. Patients were followed every 6 months for tumor recurrence.


RESULTS
Pathologically node-negative patients had a UPII RT-PCR perivesical positivity of 27% and a lymph node positivity rate of 33%. All 22 UPII RT-PCR node-negative patients were pathologically node-negative and all 13 with pathologically positive nodes had positive UPII RT-PCR lymph node signals. In all, 46% of UPII RT-PCR lymph node-positive patients were pathologically node-negative and 5% of pathologically node-negative/UPII RT-PCR node-negative patients had disease recurrence, whereas 91% of pathologically node-negative/UPII RT-PCR node-positive patients (P < .001) recurred. UPII RT-PCR node positivity was a significant predictor of tumor recurrence in multivariate analysis


CONCLUSIONS
Molecular determination of lymph node metastases by UPII RT-PCR node positivity apparently identifies patients with a poor prognosis and may be more predictive of disease recurrence than conventional pathologic analysis.
Copp
Hillary L
HL
Department of Urology, University of Virginia, Charlottesville, Virginia, USA.
Chin
Joseph L
JL
Conaway
Mark
M
Theodorescu
Dan
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D060170:Uroplakin II; D019459:Urothelium / Q000473:pathology*
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D012333:RNA, Messenger; C554658:UPK2 protein, human; D060170:Uroplakin II