235P - Panel of molecular markers for prostate cancer diagnosis

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Prostate Cancer
Translational Research
Presenter Olesya Shkabko
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors O. Shkabko1, A. Sivkov2, N. Keshishev2, O. Apolikhin2
  • 1Urological, 53 City Clinical Hospital, 105425 - Moscow/RU
  • 2Innovative, Research Institute of urology, 105425 - Moscow/RU

Abstract

Aim

The most important changes on molecular level affiliated by prostate cancer are epigenetic alterations of genetic materials including aberrant DNA methylation. We have investigated a panel of molecular markers of DNA methylation GST&pgr;1, RARß2 and RASSF1A in order to create a test-system for diagnosis and management of prostate cancer.

Methods

157 patients in age 55-70 years (67,6 ± 7,7) with PSA level 4-10 ng/ml were included in our prospective study. Patients with prostatic cancer were also subdivided according to their Gleason score, PSA, age and TNM Staging. Blood, urine samples collected after digital rectal examination (DRE) and prostate tissue received by biopsy were used like biological materials. We assessed methylation of GST&pgr;1, RARß2 and RASSF1A using a methylation-specific PCR assay and analyzed the sensitivity, specificity, positive predictive value and negative predictive value of each assay for the detection of genetic or epigenetic changes in circulating DNA.

Results

Analyzed diagnostic characteristics of a molecular markers` panel calculated on batch of DNA samples excreted from prostate tissue, test-sensitivity was 86.3%, specificity was 76.6%. Sensisitivity of markers calculated on batch of DNA samples excreted from urine was 72.5% and specificity was 44.6%. Sensitivity of markers calculated on batch of DNA samples excreted from blood was 67.1% and specificity was 52.2%, from lymphocytes - 66% and 61.7% respectively. Statistical analysis did not reveal a significant correlation between panel of markers hypermethylation and Gleason score, PSA, age or TNM staging.

Conclusions

Our data demonstrated the existence of significant differences in specificity between our diagnostic panel of markers and PSA. Specificity of markers GST &pgr;1, RARß2 and RASSF1A exceed specificity of PSA in «gray» zone (4-10 ng/ml) (61.7% vs 17%, р < 0.05). Excretion of DNA samples from prostate tissue, lymphocytes and blood was the most effective. Combined application of GST &pgr;1, RARß2, RASSF1A and PSA markers will facilitate more accurate diagnosis of prostate cancer.

Disclosure

All authors have declared no conflicts of interest.