Tissue PCA3 Evaluation in Prostate Cancer by In-Situ Hybridization
Joshua Warrick, Nallasivam Palanisamy, Allison Young, Javed Siddiqui, Angela Wu, Rohit Mehra, Shannon Carskadon, John Wei, Arul Chinnaiyan, Scott Tomlins, L Priya Kunju. University of Michigan, Ann Arbor, MI
Background: The PROGENSA PCA3 assay, an FDA approved urine based assay for assessing the risk of prostate cancer (PCa) on rebiopsy, quantifies the non-coding transcript PCA3, which is over-expressed in >95% of all prostate cancers. As tissue evaluation of PCA3 with immunohistochemistry (IHC) is not feasible, we evaluated tissue PCA3 expression by RNA-ISH (in-situ hybridization) in PCa, HGPIN, and benign mimics (including adenosis and atrophy) at radical prostatectomy (RP). We also correlated tissue PCA3 expression in PCa with ERG status by IHC.
Design: Of 301 men presenting for biopsy with pre-biopsy urine PCA3 and T2:ERG levels, 41 men underwent RP. All prostatectomies were mapped. PCA3 ISH was scored as 0-4 per RNAscope scoring Criteria (Advanced Cell Diagnostics) for all evaluable PCa foci, HGPIN, atrophy, adenosis, and benign glands. PCA3 ISH scores >1 were considered positive. For each case, total number, greatest linear dimension, Gleason score, total PCA3 score (sum of scores of each PCa focus), and total PCA3-positive linear tumor dimension were documented. Correlations with urine PCA3 and ERG IHC (EPR 3864) status of PCa foci were performed.
Results: The 41 radical prostatectomies had a median of 3 tumor foci (range 1-11) and median total linear tumor dimension 2.6 cm (SD 1.4 cm). The median urine PCA3 was 40 (SD 38, range 3-186). The sensitivity of PCA3 ISH for PCa was 54% alone and 70% when combined with ERG. 88% and 95% of patients had at least one PCa focus positive with PCA3 alone, and either PCA3 or ERG, respectively. The majority of HGPIN foci (70%) adjacent to PCa were positive with PCA3. PCA3 ISH specificity was >99% for PCa and HGPIN combined (only one benign gland showed focal staining; all adenosis and atrophy were negative). Index nodule size and total linear tumor dimension correlated with PCA3 ISH score (p<0.01). Urine PCA3 showed positive, but non-significant, correlation with total PCA3 score (rs=0.21, p=0.19,) and PCA3 positive linear tumor size (rs=0.09, p=0.57). Only 2/18 (11%) cases with PCA3 ISH score <6 had urine PCA3 >60, while cases with PCA3 score >6 showed a broad range of urine PCA3. PCA3 ISH in PCa foci positively correlated with ERG IHC status (p<0.01).
Conclusions: The sensitivity of PCA3 ISH for PCa detection is similar to that of ERG. Combined PCA3 ISH and ERG improves sensitivity of PCa detection over either marker alone. PCA3 RNA ISH is highly specific for PCa and HGPIN. Although no statistically significant correlation between urine PCA3 and total PCA3 score was seen in this cohort, concurrent low total PCA3 score and high urine PCA3 was a rare finding.
Category: Genitourinary (including renal tumors)
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 165, Monday Morning