Prospective evaluation of the prognostic relevance of molecular staging for urothelial carcinoma

Cancer. 2006 Jul 1;107(1):60-6. doi: 10.1002/cncr.21953.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma / diagnosis*
  • Carcinoma / pathology
  • Carcinoma / surgery
  • Disease-Free Survival
  • Female
  • Humans
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Recurrence, Local*
  • Neoplasm Staging
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery
  • Uroplakin II
  • Urothelium / pathology*

Substances

  • Biomarkers, Tumor
  • Membrane Proteins
  • RNA, Messenger
  • UPK2 protein, human
  • Uroplakin II