Correlation of Urine TMPRSS2: ERG and PCA3 to ERG+ and Total Prostate Cancer Burden
Allison M Young, Nallasivam Palanisamy, Javed Siddiqi, John T Wei, David Wood, Arul M Chinnaiyan, Lakshmi P Kunju, Scott A Tomlins. University of Michigan, Ann Arbor, MI; University of Michigan Medical School, Ann Arbor, MI; Univeristy of Michigan Medical School, Ann Arbor, MI
Background: ERG rearrangement, (most commonly resulting in TMPRSS2:ERG (T2:ERG) gene fusions), have been identified in approximately 50% of prostate cancers (PCa) and to date is the most specific prostate cancer biomarker. Quantification of T2:ERG in post-DRE urine, in combination with PCA3, improves the serum PSA performance for PCa prediction on biopsy. Previously, we have shown significant correlation between urine T2:ERG and maximum index tumor nodule dimension at prostatectomy.
Here we compared urine T2:ERG and PCA3 to both ERG+ and overall tumor burden at prostatectomy to assess the cancer specificity of these urine biomarkers.
Design: Of 301 men presenting for biopsy assessed by transcription mediated amplification (TMA) for T2:ERG and PCA3, 41 (14%) underwent prostatectomy. All prostatectomies were mapped and all tumor nodules (including suspicious foci) were immmunostained with an ERG antibody shown to be sensitive and specific for ERG rearranged cancer (EPR3864). For each prostatectomy, the total number, greatest linear dimension, Gleason score and ERG IHC status of all tumor nodules was documented. Correlations between clinicopathological data and urine T2:ERG and PCA3 were determined.
Results: The 41 prostatectomies had a median of 3 tumor nodules (1-15) and 2.7 cm of total linear tumor dimension (0.5-7.1 cm). There was no significant difference between the number (p=0.59) or linear tumor dimension (1.2 cm vs. 0.9 cm, p=0.36) of ERG+ and ERG- nodules (p=0.59). Urine T2:ERG most correlated with the number of ERG+ foci and total ERG+ linear tumor dimension (both rs=0.67, p<0.0001). Of patients with 0 cm, >0.1 to 1.0 cm, and >1.0 cm of total ERG+ linear tumor dimension, 1/8 (13%), 4/10 (40%) and 21/23 (91%) had urine T2: ERG >30. Urine PCA3 showed weaker correlation with both tumor nodule number (rs=0.37, p=0.02) and total linear tumor dimension (rs=0.27, p=0.08).
Conclusions: We demonstrate a strong correlation between urine T2:ERG and total ERG+ tumor burden at prostatectomy. The weaker correlation between urine PCA3 and total tumor volume suggests that this biomarker may be less cancer specific than T2:ERG. Hence, urine T2: ERG may be useful for risk stratifying men with elevated serum PSA, prior negative biopsy, or those considering active surveillance.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 178, Monday Afternoon