Prostate Adenocarcinomas Aberrantly Expressing p63 Are Negative for ERG Protein Expression and ERG Gene Rearrangement
Tamara L Lotan, Michael C Haffner, Jessica L Hicks, Adeboye O Osunkoya, George J Netto, Angelo M De Marzo, Jonathan I Epstein. Johns Hopkins School of Medicine, Baltimore, MD; Emory University School of Medicine, Atlanta, GA
Background: We have recently described a group of prostatic adenocarcinomas (PCa) that show diffuse expression of p63, a protein present in prostatic basal cells and absent from the vast majority of PCa. Despite positivity for basal markers p63 and bcl-2, these tumors also express a number of luminal markers, with uniform expression of androgen receptor (AR) and positivity for luminal cytokeratins rather than high molecular weight basal-type keratins. Given that these tumors express AR and androgen-regulated PSA and that androgen-induced gene rearrangements involving the ERG locus occur in nearly half of typical acinar PCa, we investigated whether p63-expressing PCa also harbor ERG gene rearrangements.
Design: A total of 27 p63-expressing tumors, including 12 radical prostatectomy specimens, 14 needle biopsies and one transurethral resection of the prostate (TURP), were immunostained to determine presence or absence of nuclear ERG protein. Additionally, fluorescence in situ hybridization (FISH) using a break apart probe for 5' and 3' ERG was performed on a tissue microarray (TMA) constructed from a subset of 7 of the radical prostatectomy specimens. These cases were scored for presence of ERG gene rearrangement through deletion or translocation.
Results: None of the 27 p63-expressing PCa cases expressed nuclear ERG protein by immunohistochemistry (0/27), despite the fact that adjacent endothelial cells were strongly positive, providing an internal positive control in all cases. Consistent with lack of ERG protein expression, FISH was negative for ERG gene rearrangement in the subset of all 7 p63-expressing tumors tested (0/7). Compared to a control group of more than 800 cases of usual acinar PCa at our institution, where approximately one half of all cases are positive for ERG protein and harbor ERG gene rearrangement, absence of ERG protein expression in all 27 p63-expressing cases was highly statistically significant (p<0.001).
Conclusions: Prostate tumors with aberrant p63-expression comprise an unusual subgroup with a mixed luminal and basal immunophenotype. Despite an apparently intact androgen signaling axis, these tumors completely lack ERG protein expression, and in a subset, we have confirmed that this is due to lack of ERG gene rearrangement. This data strongly suggests that p63-expressing PCa represents a molecularly distinct subclass of PCa. Further study of this rare tumor type may yield important insights into the role of p63 in prostatic epithelial and tumor biology.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 173, Monday Afternoon