Regional Variation in Epigenetic Patterns in Prostate Cancer.
Fatima Z Aly, Jeffrey C Hanson, Wusheng Yang, Matthew S Kreitman, Maria J Merino, Marston W Linehan, Peter A Pinto, Lisa G Adams, Holly S Stevenson, Daniel C Edelman, Michael R Emmert-Buck, Jaime Rodriguez-Canales. National Cancer Institute, Bethesda, MD
Background: GSTP1 gene promoter methylation is present in >90% of prostate cancers. Using laser microdissection (LCM) mapping of a prostatectomy specimen with cancer, we found that cancer epithelium was methylated throughout the gland, whereas the cancer associated stroma (CAS) was methylated only at the apical pole. At present, it is not known if this epigenetic pattern is a common feature of prostate cancer, whether it correlates with reactive stroma, or if methylation patterns are unique to individual tumor clones. The goals of the present study were to expand the LCM-based epigenetic mapping strategy to additional cases.
Design: Four radical prostatectomy specimens containing cancers that extended from apex to base were analyzed. LCM mapping included normal and cancer epithelium, and normal stroma and CAS. Pyrosequencing of the GSTP1 gene promoter was used to quantify the percentage of methylation in each sample. Whole-genomic amplification (WGA) and comparative genomic hybridization (CGH) were used for clonal analysis of cancer cells from the apex and base of the tumors. Masson stain was used to analyze the grade of reactivity of the CAS.
Results: Cancer epithelium showed variable but generally high GSTP1 methylation, ranging from 21 to 98%. A second case showed methylation (20%) of the CAS in the apical pole, similarly to our previously reported case. CGH data showed that tumors at the apex and base of the gland share the same clonal origin. Masson staining showed no differences in stromal reactivity at the apex or base of the tumors.
Conclusions: These results suggest that prostate cancers extending from apex to base within a gland can have the same clonal origin yet show regional variations in their methylation patterns. These findings are important for both the application of DNA methylation assays to prostate biopsies and to the understanding of basic prostate cancer biology.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 1:00 PM
Poster Session II # 139, Monday Afternoon