Abstract 3425: Prognostic significance of BRMS1 promoter methylation in operable breast cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 72; no. 8_Supplement; p. 3425
• Main Authors: Chimonidou, Maria, Stathopoulos, Efstathios, Georgoulias, Vasilis, Lianidou, Evi S.
• Format: Journal Article
• Language: English
• Published: 15.04.2012
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-3425

Abstract Backround: Breast Cancer Metastasis Suppressor gene-1 (BRMS1) suppresses breast cancer metastasis in multiple experimental models by reducing solitary cell survival and inhibiting growth initiation. Loss of BRMS1 expression has been shown to predict reduced disease-free survival in subsets of breast cancer patients. The BRMS1 promoter region contains a promoter-associated CpG island (CGI) that encompasses the transcriptional start site.The aim of our study was to investigate the methylation status of BRMS1 in breast tumors (FFPES) of operable breast cancer patients and evaluate its prognostic significance. Patients and methods: Using methylation-specific PCR (MSP), we examined BRMS1 promoter methylation in 116 fixed paraffin-embedded tissues (FFPEs): 5 pairs of breast tumors and their surrounding non-cancerous tissues, 4 non-cancerous tissues, 10 benign breast tumors (fibroadenomas), 10 normal breast tissues and 82 breast tumors. All breast tumors were isolated from patients with operable breast cancer. Results: Methylation of BRMS1 promoter was observed in 0/19 (0%) noncancerous breast tissues, in 0/10 (0%) benign breast tumors (fibroadenomas) and in 31/82 (37.8 %) breast cancer tumors. During the follow-up period 22/82 (26.8%) patients relapsed and 20 (24.4%) patients died. BRMS1 methylation was detected in 13/22 (59.1%) patients that relapsed and in 12/20 (60.0%) of patients who died. Disease-free interval (DFI) and overall survival (OS) were significantly associated with BRMS1 promoter methylation (P=0.007). Conclusion: We show for the first time that BRMS1 promoter methylation status in FFPEs from operable breast cancer patients provides important prognostic information and merits to be further evaluated and validated in a larger cohort of patients. This finding is consistent with other studies that showed significant down-regulation of BRMS1 in some breast tumors, especially in metastatic disease, because of epigenetic silencing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3425. doi:1538-7445.AM2012-3425