HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Ribonucleotide reductase subunit M1 expression in resectable, muscle-invasive urothelial cancer correlates with survival in younger patients.

AbstractOBJECTIVE:
To assess whether high ribonucleotide reductase subunit M1 (RRM1) expression in patients with resected, muscle-invasive (T2-4NxM0) urothelial carcinoma (UC) correlated with longer overall survival (OS). RRM1 is the primary cellular target of gemcitabine and previous studies in resected early-stage lung cancer have shown a survival benefit for patients with high expression.
PATIENTS AND METHODS:
In all, 84 radical cystectomy specimens with muscle-invasive UC were identified from existing tissue microarrays. The patients' medical records were retrospectively reviewed to confirm pathology and stage. Specimens were analysed for RRM1 expression using automated quantitative analysis. The median value of RRM1 was established a priori as the threshold for high and low expression.
RESULTS:
The median age of the patients was 69 years. Stages were nearly equally distributed: 30%, 38%, and 32% for stage II, III, and IV, respectively. Most were high grade (99%) with no nodal involvement (69%). The median (range) OS was 2.0 (0-13.1) years. Tumoral RRM1 levels did not correlate with OS for the entire cohort, but when adjusted for age, high tumoral RRM1 expression in younger patients (aged <70 years) correlated with increased survival. Younger patients with high RRM1 expression had a median OS of 10.6 years compared with 1.6 years in older patients (P= 0.001). There was no difference in OS among low RRM1 expressors: 2.3 vs 1.6 years in younger and older patients, respectively (P= 0.22).
CONCLUSIONS:
Our results suggest that high RRM1 expression may be prognostic for improved survival in patients with muscle-invasive UC aged <70 years.
AuthorsLauren C Harshman, Gerold Bepler, Zhong Zheng, John P Higgins, Genevera I Allen, Sandy Srinivas
JournalBJU international (BJU Int) Vol. 106 Issue 11 Pg. 1805-11 (Dec 2010) ISSN: 1464-410X [Electronic] England
PMID20438561 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.
Chemical References
  • RRM1 protein, human
  • Tumor Suppressor Proteins
Topics
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Carcinoma, Transitional Cell (metabolism, mortality, pathology, therapy)
  • Cohort Studies
  • Cystectomy
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Tumor Suppressor Proteins (metabolism)
  • Urinary Bladder Neoplasms (metabolism, mortality, pathology, therapy)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: