Characterization of ERG Rearrangements, PTEN and SPINK1 Expression in Hormone Refractory Prostate Cancer Associated with Lethal Disease
A Bakkar, M Yoshimoto, S Liu, Q Duan, K Sircar, JA Squire, TA Bismar. University of Calgary and Calgary Laboratory Services, Calgary, AB, Canada; Queens University and Kingston General Hospital, Kingston, ON, Canada; Tom Baker Cancer Center, Calgary, AB, Canada; MD Anderson Cancer Center, Houston, TX
Background: Recent expression studies suggest that a molecular classification of prostate cancer (PCA) based on ERG rearrangement status is possible. Additional molecular makers of similar charesteristics include PTEN genomic deletions, SPINK1 expression and AR status. Hormone refractory prostate cancer (HRPCA) is considered an end stage of disease progression and is associated with cancer specific death in the vast majority of cases. Here, we investigate their association and relation to cancer specific death in a cohort of HRPCA.
Design: Initial cohort of 59 HRPCA samples representing locally advanced tumors obtained by TURP was assembled onto TMA. ERG gene rearrangements (131 core), PTEN deletions (96 core) and AR copy number (74 core) were interrogated by FISH. SPINK1 (125 core) was evaluated by IHC.
Results: ERG rearrangements and PTEN deletions were detected in 18/54 (33.3%) and 26/39 (66.6%) of the cases, with 13/18 (72%) of the ERG rearrangements occurring by deletions rather than insertion. SPINK1 overexpression was present in 4/51 (7.8%) of cases occurring exclusively in ERG non rearranged tumors. In this cohort, cases with hemizygous and homozygous PTEN deletions occurred simultaneously in (2/10) 20% and (7/16) 43.7% of patients. Increased AR copy number was identified in 5/25 (25%) of cases. Accounting for individual core status; PTEN deletions were significantly associated with each of ERG rearrangements (p=0.019), SPINK1 overexpression (p=0.026) and AR copy number (p=0.003). However, none of the SPINK1 overexpressing cores showed increased AR copy number (0/19) (p=0.061). Finally, only PTEN status (no deletions vs. hemizygous vs. homozygous deletions) was associated with death of disease (p=0.009).
Conclusions: Significant interplay exists between PTEN deletions and each of ERG rearrangements, AR copy number and SPINK1 overexpression in HRPCA. No single marker is by itself able to correlate with cancer specific death which likely reflects the heterogeneous nature of HRPCA. However, complete loss of PTEN seems to play more significant role in advanced PCA as evidenced by its association with cancer specific death.
Category: Genitourinary (including renal tumors)
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 133, Wednesday Afternoon