Immunohistochemical Characterization of Gleason Pattern 4-Associated Pattern 3 Prostate Cancer
Ashley Ward, Adam Sowalsky, Liza Quintana, Steven Balk, Huihui Ye. Beth Israel Deaconess Medical Center, Boston, MA
Background: Prostate cancer (PCa) are frequently multifocal and indolent in contemporary series. Extended core biopsies increase overall cancer detection rate but miss small-volume high grade tumors. One potential solution is to identify molecular signatures of Gleason pattern 3 (G3) tumors that are associated with Gleason pattern 4 and 5 (G4 and G5) tumors. Previous studies from our group revealed that TMPRSS2-ERG breakpoints of adjacent ERG(+) G3 and G4 tumors were exactly the same but distinct among individuals, suggesting they are clonally related. Adjacent G3/G4 tumors are genetically similar but may show additional PTEN loss in G4. Affymetrix arrays revealed dysregulation of a small set of genes in G3-associated G4. Among those, PTEN, neuropilin-2 (NRP2), B lymphoma Mo-MLV insertion region 1 homolog (BMI1), and IGF-1 receptor (IGF-1R), which had been shown to cross-talk and promote progression of PCa, showed a reasonable correlation in our array data.
Design: Slides of radical prostatectomy specimens of localized PCa without prior treatment from 2010 to 2012 were retrieved and mapped for all tumor foci. Study group consists of 22 cases with an index tumor of Gleason score 7 (3+4 or 4+3) and separate foci of Gleason score 6 tumor. Control group consists of 9 cases with a final Gleason score 6. PIN-4, ERG, PTEN, NRP2, BMI1, and IGF-1R immunostains are performed on consecutive sections.
Results: Study cases contained 22 index tumors of Gleason 7 and 43 distant foci of Gleason 6 tumors (1 to 8 foci per case). 9 control cases contained 10 tumor foci of Gleason 6 tumors. In the study group, adjacent G3 and G4 tumors showed 100% concordance in ERG expression, indicating a common clonal origin. 15 of 43 (34.9%) distant G3 foci showed a discordant ERG expression compared to the index tumors. Among 75 tumors in all cases, 61 foci of tumor-associated high grade PIN were identified in 47 tumors. 53 of 61 (86.9%) PIN demonstrated a concordant ERG expression as their adjacent tumors. PTEN loss was detected in 6 of 22 (27.3%) Gleason 7 tumors and 0 of 43 co-existing Gleason 6 tumors in the study group, and 0 of 10 Gleason 6 tumors in the control group, respectively. PTEN loss was present in some Gleason 7-associated PIN. No PTEN loss was seen in any benign tissue or non-tumor associated PIN.
Conclusions: PTEN loss may be one of the molecular signatures of G4-associated G3 tumors. PTEN stain results need to be validated with increased sample size and correlated with FISH findings. NRP2, BMI1, and IGF-1R immunostains are under progress, which may reveal more candidates to characterize aggressive G3 tumors.
Category: Genitourinary (including renal tumors)
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 143, Wednesday Afternoon