[1009] Immunohistochemical Analysis of Speckle-Type POZ Protein (SPOP) in Prostate Cancer, High Grade Prostatic Intraepithelial Neoplasia and Benign Glands

Aria Razmaria, Joshua Cohn, Kevin White, Donald VanderGriend, Gladell P Paner. University of Chicago, Chicago, IL

Background: Recent deep whole-exome sequencing studies of prostate cancer tissues demonstrate that SPOP is the most frequently mutated gene, with mutations in 6-15% of localized and advanced tumors (Nat Genet 2012). Prostate cancers with mutant SPOP lack the ETS family gene rearrangements and may define a new molecular subtype of prostate cancer. SPOP is a cullin 3-based E3 ubiquitin ligase adaptor localized in the nucleus and has been described to inhibit steroid receptor co-activator-3-mediated oncogenic signaling and tumorigenesis, thus positioning SPOP as a tumor suppressor.
Design: We used SPOP-5G antibody (Liu et al., Science 2009) to immunostain prostate cancer tissue microarrays containing samples of 111 prostate cancers paired with benign tissues where available as well as high-grade prostatic intraepithelial neoplasia (HGPIN). Assessment of nuclear staining positivity and distribution of positive reaction was performed by 1 pathologist.
Results: Table 1 summarizes the observed nuclear staining and distribution. Examined samples exhibited strong nuclear staining in 26% of tissues overall. The stratification according to Gleason score showed similar distribution with 19-29% strong nuclear positivity across all Gleason scores with sufficient representation. Of note, also benign tissues as well as HGPIN tissues from the same samples stained positive for SPOP as well. The quantification analysis reveals that not all malignant or benign tissue stains positive or stains positive to the same extent.

    Distribution of positive reaction
 OverallSPOP negativeSPOP positive5-15%16-50%>50%
Whole cohort111*82 (74%)29 (26%)13 (45%)7 (24%)9 (31%)
3+34935 (71%)14 (29%)7 (50%)4 (29%)3 (21%)
3+42820 (71%)8 (29%)4 (50%)1 (12%)3 (38%)
4+32117 (81%)4 (19%)2 (50%)1 (25%)1 (25%)
4+454 (80%)1 (20%)001
3+5110---
4+5110---
5+4110---
5+5220---
HGPIN2318 (78%)5 (22%)01 (20%)4 (80%)
Benign glands8568 (80%)12 (20%)6 (35%)3 (18%)8 (47%)
*2 specimens with benign glands and HGPIN only


Conclusions: SPOP is expressed in a subset of prostate cancer but with no correlation to the Gleason grade. The observed staining pattern corresponds on the phenotypic level with the recently described SPOP gene mutation frequency in prostate cancer tissues. The observed staining of benign tissue as well as HGPIN indicates an early event in the tumorigenesis and may also support the concept of "field effect" in development of prostate cancer.
Category: Genitourinary (including renal tumors)

Wednesday, March 6, 2013 9:30 AM

Poster Session V # 128, Wednesday Morning

 

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