The relationship between the number of aberrantly methylated regions and the methylation status of p73 and RARB genes and prognosis in patients with breast cancer

MARZESE D.M.; GAGO F.E.; OROZCO J.I.; TELLO O.M.; VARGAS ROIG L.M.; ROQUÉ M.

Chicago

Congreso; 47th Annual Meeting of the American Society for Clinical Oncology; 2011

American Society for Clinical Oncology

Background: Invasive ductal carcinoma (IDC) is the most frequent type of human breast cancer. Despite sharing a common origin, a great variation is observed among patients´ outcome, which can be explained by their genetic and epigenetic differences. The most commonly reported epigenetic alteration is the aberrant methylation of CpG islands. In previous reports we have shown that the tumor methylation profile (TMP) is specific for each breast cancer patient. Here we evaluate the epigenetic differences between IDCs from patients with good and poor prognosis. Methods: The methylation status of 49 cancer-related regions was studied in seventy patients bearing IDC using the Methyl Specific-MLPA assay. Statistical associations were determined by chi square test and the strength of associations was assessed by Phi and Cramer´s V coefficients. Statistical correlations were established by Pearson´s r and Spearman´s rho coefficients. Results: Tumors with increased number of methylated cancer-related regions correlate with high histological grade (p=0.002) and high proliferation rate (p<0.001). The methylation of p73 is strongly associated with high histological grade (p<0.001). The methylation of RARB is associated with high histological grade (p=0.003), positive lymph nodes (p<0.001) and high tumor size (p=0.021). Finally, the concurrent methylation of p73 and RARB is associated with high histological grade (p<0.001), high proliferation rate (p=0.002), positive lymph node (p=0.006) and elevated Nottingham Prognostic Index (p<0.001). Conclusions: We demonstrate that the aggressiveness of IDCs can be epigenetically distinguished by quantitative and qualitative DNA methylation analyzes. The number of aberrantly methylated genes and the methylation status of p73 and RARB could contribute to predict the prognosis of breast cancer patients.