Impact of the expression of Aurora-A, p53, and MIB-1 on the prognosis of urothelial carcinomas of the upper urinary tract

Urol Oncol. 2012 Mar-Apr;30(2):182-7. doi: 10.1016/j.urolonc.2009.12.003. Epub 2010 Mar 2.

Abstract

Objectives: To investigate whether overexpression of p53, MIB-1, and Aurora-A on protein level played a role in the relapse of urothelial carcinomas of the upper urinary tract (UC-UUT).

Materials and methods: The following data from the files of 42 patients treated for UC-UUT were collated: age, prior history of cancer, tumor stage and grade, and disease progression. Immunohistochemistry (IHC) for p53, MIB-1, and Aurora-A was performed on tissue microarray sections from tumor tissue.

Results: Patients aged 46 to 100 years (mean 70.6 years). Overall, 23 (54%) patients died from progression of UT-UCC. The surgical stage was significantly associated with MIB-1 and Aurora-A overexpression (P = 0.004 for each). Univariate analysis showed that relapse was significantly associated with ureteral localization (P = 0.02), the presence of vascular invasion (VI) (P = 0.003), high grade (P = 0.04), high stage UT-UCCs (P = 0.02), and p53 (P = 0.01), Aurora-A (P = 0.01), and MIB-1 overexpression (P = 0.02). In multivariate analysis, relapse was associated with high grade (P = 0.04), high stage (P = 0.04), VI (P < 0.0001, respectively), and p53 (P = 0.04) and Aurora-A (P = 0.02) overexpression but not with MIB-1 overexpression (P = 0.06). In addition, expressions of p53, MIB-1, and Aurora-A were significantly associated with presence of VI (P = 0.008, P = 0.001, and P = 0.003, respectively).

Conclusion: Aurora-A and p53 are important factors in UC-UUT development and might be useful as independent factors for predicting clinical outcome and presence of VI. Aurora-A seems to influence the development of VI and tumor aggressiveness via a mechanism not clearly elucidated yet.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aurora Kinases
  • Biomarkers, Tumor / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Protein Serine-Threonine Kinases / metabolism*
  • Survival Rate
  • Tissue Array Analysis
  • Tumor Suppressor Protein p53 / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*
  • Urologic Neoplasms / metabolism*
  • Urologic Neoplasms / mortality
  • Urologic Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MIB1 ligase, human
  • Ubiquitin-Protein Ligases
  • Aurora Kinases
  • Protein Serine-Threonine Kinases