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: Magdalini Kioulafa, Ioanna Balkouranidou, Georgia Sotiropoulou, Loukas Kaklamanis, Dimitris Mavroudis, Vassilis Georgoulias, Evi S Lianidou
• Journal: International journal of cancer (Int J Cancer) Vol. 125 Issue 12 Pg. 2887-92 (Dec 15 2009) ISSN: 1097-0215 [Electronic] United States
• PMID: 19551853 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 UICC.

Chemical References

• Biomarkers, Tumor
• CST6 protein, human
• Cystatin M
• DNA, Neoplasm

Topics

• Biomarkers, Tumor
• Breast (metabolism, pathology)
• Breast Neoplasms (genetics, pathology, surgery)
• Carcinoma, Lobular (genetics, pathology, surgery)
• Cystatin M (genetics)
• DNA Methylation
• DNA, Neoplasm (genetics)
• Female
• Fibroadenoma (genetics, pathology, surgery)
• Gene Expression Regulation, Neoplastic
• Humans
• Neoplasm Recurrence, Local (genetics, pathology, surgery)
• Polymerase Chain Reaction
• Prognosis
• Promoter Regions, Genetic (genetics)
• Survival Rate