Methylation profile of ER and HER2 negative (ER-/HER2-) breast tumors.

BRANHAM MARIA T; MARZECE DIEGO; GAGO FRANCISCO; TELLO OLGA; OROZCO JAVIER; VARGAS ROIG L; ROQUÉ MARIA

Chicago, Illinois

Congreso; 2011 Annual Meeting of the American Society of Clinical Oncology; 2011

Background: Breast cancer is a collection of clinically, histopathologically and molecularly heterogeneous diseases, with diverse outcomes and responses to treatment. ER-/HER2- is an immunohistochemical description of breast cancers with a double negative staining for ER and HER2. These tumors have an aggressive clinical behavior and poor prognosis. The hypermethylation of CpG islands (CpGI) is a common epigenetic alteration for suppressing gene expression in breast cancer. Understanding how these epigenetic changes are involved in tumor progression is important for a better comprehension of tumor biology. Here we evaluated the methylation status of ER-/HER2- compared to luminal breast tumors. Methods: For the methylation analysis, we used the methyl specific-multiplex ligation probe amplification assay. Seventy invasive ductal carcinomas (IDC) were included in the study. In 20 IDCs we analyzed 127 CpGI and in 50 IDCs we analyzed 49 CpGI. Results: Among the islands studied we found positive association between ER-/HER2- tumors and methylated MGMT (p0.002) and CD44 (p0.01) and non methylated GSTP1(p0.04), PAX6 (p0.04), MSH2 (p0.002), MSH3 (p0.001) and CACNA1A (p0.049) genes. Conclusions: ER-/HER2- cancers present a clearly different methylation profile, compared to luminal tumors. These results could add knowledge to the behavior of these tumors and improve future treatment options