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


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.


CONCLUSIONS
KLK10 exon 3 methylation provides important prognostic information in early breast cancer patients.
Kioulafa
M
M
Department of Chemistry, Laboratory of Analytical Chemistry, University of Athens, Athens, Greece.
Kaklamanis
L
L
Stathopoulos
E
E
Mavroudis
D
D
Georgoulias
V
V
Lianidou
E S
ES
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C100936:KLK10 protein, human; D007610:Kallikreins