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Annals of Oncology Advance Access published online on January 15, 2009
Annals of Oncology, doi:10.1093/annonc/mdn733
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

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

M. Kioulafa1, L. Kaklamanis2, E. Stathopoulos3, D. Mavroudis4, V. Georgoulias4 and E. S. Lianidou1,*

1 Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens
2 Department of Pathology, Onassis Cardiac Surgery Center, Athens
3 Department of Pathology and Medical Oncology
4 Department of Medical Oncology, University General Hospital of Heraklion, Crete Greece

* Correspondence to: Dr E. S. Lianidou, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens 15771, Greece. Tel: +30-210-7274319; Fax: +30-210-7274750; E-mail: lianidou{at}chem.uoa.gr

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.

DNA methylation, early breast cancer, epigenetic markers, KLK10, methylation-specific PCR, prognostic biomarker

Received for publication October 1, 2008. Accepted for publication November 4, 2008.


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