Survivin is an independent prognostic marker for risk stratification of breast cancer patients

Clin Chem. 2004 Nov;50(11):1986-93. doi: 10.1373/clinchem.2004.039149. Epub 2004 Sep 13.

Abstract

Background: Results in previous qualitative studies of the association of the apoptosis inhibitor survivin with prognosis of breast cancer patients have been contradictory.

Methods: Survivin mRNA was measured by quantitative TaqMan reverse transcription-PCR in 275 breast cancer tissues from patients with operable tumors and was correlated with established clinicopathologic factors, relapse-free survival [(RFS); 102 events], and overall survival [(OS); 81 events].

Results: High survivin mRNA concentrations were found mainly in tissues from younger patients and in high-grade cancer tissues. High survivin concentrations were most strongly associated with estrogen receptor- or progesterone receptor-negative tumors. In univariate Cox regression analysis for RFS, survivin concentrations were significantly associated with poor prognosis with a hazard ratio (HR) of 1.99 (95% confidence interval, 1.31-3.02; P = 0.001) for every 10-fold increase in expression. For OS, a significant contribution of survivin to poor prognosis was found with a HR of 2.76 (1.67-4.55; P <0.001). Multivariate analyses were performed including established clinicopathologic factors. For RFS, age (P = 0.027), nodal category (P <0.001), and survivin [HR = 1.78 (1.18-2.68); P = 0.006] contributed significantly to the model. For OS, only nodal category (P <0.001) and survivin [HR = 3.05 (1.83-5.10); P <0.001] were significant.

Conclusion: Survivin demonstrates a strong, independent, association with poor prognosis. Survivin might be used as a new marker to stratify breast cancer patients for more optimal treatment modalities, or it could be a promising new target for therapy.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / diagnosis*
  • Disease-Free Survival
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins / analysis*
  • Microtubule-Associated Proteins / genetics
  • Multivariate Analysis
  • Neoplasm Proteins
  • RNA, Messenger / analysis
  • Regression Analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Assessment
  • Survival Rate
  • Survivin

Substances

  • BIRC5 protein, human
  • Biomarkers, Tumor
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • Survivin