Kallikrein 10 (KLK10) methylation as a novel prognostic biomarker in early breast cancer

Ann Oncol. 2009 Jun;20(6):1020-5. doi: 10.1093/annonc/mdn733. Epub 2009 Jan 15.

Abstract

Background: We evaluated the prognostic significance of KLK10 exon 3 methylation in patients with early-stage breast cancer since it has been shown to have a significant impact on biological characteristics of breast tumors.

Materials and methods: Using methylation-specific PCR, we evaluated the specificity of KLK10 methylation in 10 breast tumors and matching normal tissues, 10 breast fibroadenomas, 11 normal breast tissues and in a testing group of 35 patients. The prognostic significance of KLK10 methylation was validated in an independent cohort of 93 patients.

Results: KLK10 was not methylated in normal breast tissues and fibroadenomas while it was in 5 of 10 breast tumors and in 1 of 10 matching normal tissues. In the testing group of 35 patients, KLK10 methylation was detected in 70.0% of patients who relapsed (P = 0.001) and in 77.8% of patients who died (P = 0.025). In the independent cohort, 53 of 93 (57.0%) patients were found positive for KLK10 methylation. During the follow-up period, 24 of 93 (25.8%) patients relapsed and 19 of 93 (20.4%) died. Disease-free interval (DFI) and overall survival (OS) were significantly associated with KLK10 methylation (P = 0.0025 and P = 0.003). Multivariate analysis revealed that KLK10 methylation was an independent prognostic factor for DFI and OS.

Conclusion: KLK10 exon 3 methylation provides important prognostic information in early breast cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Breast / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • DNA Methylation*
  • Female
  • Humans
  • Kallikreins / genetics*
  • Kallikreins / metabolism
  • Prognosis
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • KLK10 protein, human
  • Kallikreins