Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Dec;72(6):1234-9.
doi: 10.1016/j.urology.2007.12.060. Epub 2008 Apr 2.

Effect of DNA methylation on identification of aggressive prostate cancer

Joshi J Alumkal  1 , Zhe Zhang, Elizabeth B Humphreys, Christina Bennett, Leslie A Mangold, Michael A Carducci, Alan W Partin, Elizabeth Garrett-Mayer, Angelo M DeMarzo, James G Herman
Affiliations

Effect of DNA methylation on identification of aggressive prostate cancer

Joshi J Alumkal et al. Urology. 2008 Dec.

Abstract

Objectives: Biochemical (prostate-specific antigen) recurrence of prostate cancer after radical prostatectomy remains a major problem. Better biomarkers are needed to identify high-risk patients. DNA methylation of promoter regions leads to gene silencing in many cancers. In this study, we assessed the effect of DNA methylation on the identification of recurrent prostate cancer.

Methods: We studied the methylation status of 15 pre-specified genes using methylation-specific polymerase chain reaction on tissue samples from 151 patients with localized prostate cancer and at least 5 years of follow-up after prostatectomy.

Results: On multivariate logistic regression analysis, a high Gleason score and involvement of the capsule, lymph nodes, seminal vesicles, or surgical margin were associated with an increased risk of biochemical recurrence. Methylation of CDH13 by itself (odds ratio 5.50, 95% confidence interval [CI] 1.34 to 22.67; P = 0.02) or combined with methylation of ASC (odds ratio 5.64, 95% CI 1.47 to 21.7; P = 0.01) was also associated with an increased risk of biochemical recurrence. The presence of methylation of ASC and/or CDH13 yielded a sensitivity of 72.3% (95% CI 57% to 84.4%) and negative predictive value of 79% (95% CI 66.8% to 88.3%), similar to the weighted risk of recurrence (determined from the lymph node status, seminal vesicle status, surgical margin status, and postoperative Gleason score), a powerful clinicopathologic prognostic score. However, 34% (95% CI 21% to 49%) of the patients with recurrence were identified by the methylation profile of ASC and CDH13 rather than the weighted risk of recurrence.

Conclusions: The results of our study have shown that methylation of CDH13 alone or combined with methylation of ASC is independently associated with an increased risk of biochemical recurrence after radical prostatectomy even considering the weighted risk of recurrence score. These findings should be validated in an independent, larger cohort of patients with prostate cancer who have undergone radical prostatectomy.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Gel Illustrating MSPCR Reaction
IVD=In vitro methylated DNA, the methylated control; NL=Normal lymphocytes, the unmethylated control; PC1, 2, 3=Prostate cancer samples; U=Unmethylated reaction, M=Methylated reaction
See this image and copyright information in PMC

References

    1. American Cancer Society. Cancer Facts and Figures. 2007.
    1. Brawer MK, Chetner MP, Beatie J, Buchner DM, Vessella RL, Lange PH. Screening for prostatic carcinoma with prostate specific antigen. J Urol. 1992;147:841–845. - PubMed
    1. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural history of progression after PSA elevation following radical prostatectomy. Jama. 1999;281:1591–1597. - PubMed
    1. Roberts WW, Bergstralh EJ, Blute ML, Slezak JM, Carducci M, Han M, Epstein JI, Eisenberger MA, Walsh PC, Partin AW. Contemporary identification of patients at high risk of early prostate cancer recurrence after radical retropubic prostatectomy. Urology. 2001;57:1033–1037. - PubMed
    1. Kattan MW, Eastham JA, Stapleton AM, Wheeler TM, Scardino PT. A preoperative nomogram for disease recurrence following radical prostatectomy for prostate cancer. J Natl Cancer Inst. 1998;90:766–771. - PubMed

Publication types

Substances