Prognostic value of apoptosis-related markers in urothelial cancer of the upper urinary tract

Hum Pathol. 2009 May;40(5):668-77. doi: 10.1016/j.humpath.2008.10.010. Epub 2009 Jan 20.


We investigated the expression of apoptosis-related markers and their association with the clinical outcomes of patients with urothelial carcinoma of the upper urinary tract. A total of 112 patients with urothelial carcinoma of the upper urinary tract that had surgery from March 1998 to July 2005 were included in the study. Tissue microarray slides were used for immunohistochemistry, and immunohistochemical staining was performed to investigate the association of apoptosis-related markers with clinical outcome. Apoptosis was confirmed by the TdT-mediated DUTP nick-end labeling method to obtain the apoptotic index. Survival analysis was performed according to the Kaplan-Meier method, and the Cox proportional hazard regression model was used to compare the relative influence of different prognostic factors. Among the 112 patients, 32 (28.6%) had altered expression of p53, 30 (26.8%) of bcl-2, 62 (55.4%) of bax, 27 (24.1%) of caspase-3, and 23 (20.5%) of survivin. The expression of p53 and caspase-3 was associated with the pathologic grade (P = .035 and P = .004, respectively). Altered expression of caspase-3 was associated with the pathologic stage (P = .016). The multivariate analysis showed that the expression of survivin (hazard ratio 2.91, 95% confidence interval 1.07-7.90, P = .036) and the apoptotic index (AI) (3.35, 1.06-10.56, P = .039), as well as the T and N stages (P = .043 and P = .010, respectively) were significantly associated with the disease-specific survival. Our results suggest that survivin expression and a high apoptotic index were poor prognostic factors for survival in patients with urothelial carcinoma of the upper urinary tract. These results may help to identify a subset of patients who require adjuvant therapy or closer follow-up.

MeSH terms

  • Apoptosis / physiology*
  • Biomarkers, Tumor / analysis*
  • Caspase 3 / biosynthesis
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Inhibitor of Apoptosis Proteins
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Pelvis / metabolism
  • Kidney Pelvis / pathology*
  • Male
  • Microtubule-Associated Proteins / biosynthesis
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Survivin
  • Tissue Array Analysis
  • Tumor Suppressor Protein p53 / biosynthesis
  • Ureteral Neoplasms / metabolism
  • Ureteral Neoplasms / pathology*
  • bcl-2-Associated X Protein / biosynthesis


  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Survivin
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Caspase 3