Hypermethylation of AP-2Alpha as a Prognostic Marker for DCIS

摘要

This proposal was initially based on the IDEA award concept that the abnormal gene promoter DNA methylation status of the AP2 gene might predict which DCIS lesions in women would be at risk for the evolution of recurrence and/or emergence of invasive cancer. As the work progressed the concept was expanded to include the DNA methylation status of additional genes for this purpose and also for the purpose of predicting survival outcomes in women with all stages of breast cancer. During the course of the project, we performed a small nested case control study of 71 women with DCIS from USCF of which 34 developed recurrent disease. Unfortunately, among the methylation status of the AP2, CYCLIN D, ECAD, GSTP, and SSOCS genes, either as individual genes, or in combinations, no significant odds ratios for disease occurrence emerged when the predictive value of nuclear grade was factored in. We also performed a large blinded study of over 140 women with DCIS and all stages of breast cancer in a cohort from New Mexico with extensive 5 year longitudinal follow-up. Unfortunately, for all of the above genes plus 5 others, multivariate analyses, to date, do not show significant OR's for recurrence/survival.