Tumor suppressor role of KiSS-1 in bladder cancer: loss of KiSS-1 expression is associated with bladder cancer progression and clinical outcome

Am J Pathol. 2003 Feb;162(2):609-17. doi: 10.1016/S0002-9440(10)63854-0.


The expression profiles of nine bladder cancer cell lines were compared against a pool containing equal total RNA quantities of each of them. Lower expression of KiSS-1 was revealed in cells derived from the most advanced bladder tumors. When comparing 15 primary bladder tumors versus a pool of four bladder cancer cell lines, lower transcript levels of KiSS-1 were observed in the invasive bladder carcinomas as compared to superficial tumors. KiSS-1 expression ratios provided prognostic information. The expression pattern of KiSS-1 transcripts was analyzed using in situ hybridization in nine bladder cancer cells, paired normal urothelium and bladder tumor samples (n = 25), and tissue microarrays of bladder tumors (n = 173). We observed complete loss of KiSS-1 in all invasive tumors under study as compared to their respective normal urothelium. The expression of KiSS-1 was found to be significantly associated with histopathological stage. Patients with lower KiSS-1 expression showed a direct correlation with overall survival in a subset of bladder tumors whose follow-up was available (n = 69). We did not observe any significant differential KiSS-1 expression along cell cycle by sorting analysis. A potential tumor suppressor role in bladder cancer was revealed for KiSS-1. Moreover, it showed predictive value by identifying patients with poor outcome.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / mortality
  • Carcinoma in Situ / pathology
  • Disease Progression
  • Female
  • Genes, Retinoblastoma
  • Genes, Tumor Suppressor*
  • Genes, p53
  • Humans
  • In Situ Hybridization
  • Kisspeptins
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Proteins / genetics*
  • Smoking
  • Survival Analysis
  • Time Factors
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / mortality
  • Urinary Bladder Neoplasms / pathology


  • KISS1 protein, human
  • Kisspeptins
  • Proteins
  • Tumor Suppressor Proteins