Epigenetic inactivation of TSGs by promoter hyper methylation is a frequent event during tumorigenesis. In breast cancer, the most common malignant disease in women, hypermethylation http://www.selleckchem.com/products/AP24534.html of specific genes has been associated with the response to therapy, prog nosis, invasiveness and metastasis. Hypermethy lation of TSGs in breast cancer is often associated with clinicopathological factors predicting poor prognosis and consequently serves as potential therapeutic targets for demethylating agents. However, recent data also indicate that methylation of specific TSGs can predict sensitivity to chemotherapy thus opening up the potential for DNA methylation as a biomarker to further individua lize cancer treatment in the future.

In the present study, we examined the Inhibitors,Modulators,Libraries possibility that FBXW7 hCDC4 expression is epigenetically inactivated through promoter specific hypermethylation in breast cancer, a tumor type where Fbxw7 hCdc4 mutations are not commonly observed. We also explored Inhibitors,Modulators,Libraries the possi bility that aberrant promoter methylation Inhibitors,Modulators,Libraries associates with ncer. The results demonstrate that 51% of primary breast tumor specimens have a methylated FBXW7 hCDC4 b promoter with concomitant loss of FBXW7 hCDC4 b expression. Interestingly, although methylation associ ates with high grade tumors, univariate and multivariate analysis suggest that FBXW7 hCDC4 b promoter methy lation might be a favorable prognostic marker in breast cancer. Materials and methods Tumor specimens and clinicopathological features A total of 161 primary breast tumor specimens from two breast cancer cohorts were included in this study.

Among the 161 samples in which FBXW7 hCDC4 b promoter methylation was analysed, RNA was available from 139 samples, which was further processed Inhibitors,Modulators,Libraries for cDNA synthesis and FBXW7 hCDC4 b expression ana lysis as described below. A total of 68 cases of primary breast cancer were obtained from patients diagnosed at the Department of Obstetrics and Gynecology of the Innsbruck Medical University of Austria and 93 samples were obtained from patients at the Depart ment of Pathology of Uppsala University, Uppsala, Swe den. All patients underwent resection of the tumor during surgery and specimens were processed by pathologists at the affiliated hospital. Samples were snap frozen in liquid nitrogen and stored at 80 C until RNA and DNA extraction.

Cohort 1, Clinicopathologic features for this collection of samples have been previously reported. Patients were diagnosed and operated on between 1990 and 2001 and the median age of the patients included in this study Inhibitors,Modulators,Libraries was 64 years. Patients were trea ted in compliance with the national recommendations at the time. Forty one and 27 patients underwent a lum pectomy or a mastectomy, respectively. Thirty eight patients received loco regional radiation. Thirty five patients received adjuvant combination chemotherapy CMF, and 33 patients received adjuvant anti hormonal sellekchem therapy.