title: Methylation of cystatin M promoter is associated with unfavorable prognosis in operable breast cancer.
abstract: The methylation status of cystatin M (CST6) gene in breast tumors was investigated and its prognostic significance as a novel breast cancer biomarker was evaluated. Using methylation-specific PCR (MSP), CST6 promoter methylation was examined in 134 formalin fixed paraffin-embedded tissues (FFPEs): 10 pairs of breast tumors and their surrounding normal tissues, 10 breast fibroadenomas, 11 normal breast tissues and 93 breast tumors. Methylation of CST6 promoter was observed in 2/21 (9.5%) noncancerous breast tissues, 1/10 (10%) benign breast tumors (fibroadenomas) and 52 (55.9%) operable breast cancer tumor samples. CST6 was rarely methylated in the normal tissue surrounding the tumor (10%). During the follow-up period, 24 (25.8%) patients relapsed and 19 (20.4%) died. CST6 methylation was detected in 19 (79.2%) of patients who relapsed and in 15 (78.9%) of patients who died. Disease-free-interval (DFI) and overall survival (OS) were significantly associated with CST6 promoter methylation (p=0.004 and p=0.001 respectively). Multivariate analysis revealed that CST6 methylation is an independent prognostic factor for DFI (HR=3.484; 95% CI: 1.155-10.511; p=0.027). and OS (HR=9.190; 95% CI: 1.989-42.454; p=0.004). CST6 promoter methylation status in tumor cells seems to provide important prognostic information in operable breast cancer and merits to be further evaluated and validated in a larger cohort of patients.
authors: Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, Greece.
authors: Magdalini
authors: M
authors: Kioulafa
authors: Ioanna
authors: I
authors: Balkouranidou
authors: Georgia
authors: G
authors: Sotiropoulou
authors: Loukas
authors: L
authors: Kaklamanis
authors: Dimitris
authors: D
authors: Mavroudis
authors: Vassilis
authors: V
authors: Georgoulias
authors: Evi S
authors: ES
authors: Lianidou
mesh_terms: D014408:Biomarkers, Tumor; D001940:Breast / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery*; D018275:Carcinoma, Lobular / Q000235:genetics / Q000473:pathology / Q000601:surgery; D055332:Cystatin M / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018226:Fibroadenoma / Q000235:genetics / Q000473:pathology / Q000601:surgery; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000601:surgery; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; C525104:CST6 protein, human; D055332:Cystatin M; D004273:DNA, Neoplasm