Prostate Adenocarcinomas Aberrantly Expressing p63 Have a Luminal Cell Phenotype
TL Lotan, AO Osunkoya, AM DeMarzo, GJ Netto, JI Epstein. Johns Hopkins Hospital, Baltimore, MD; Emory University School of Medicine, Atlanta, GA
Background: We have recently described a group of prostatic adenocarcinomas (PCa) that show diffuse aberrant expression of p63. Although these tumors lack high molecular weight cytokeratin expression as evidenced by absent 34E12 immunostaining, they are strongly positive for bcl-2, a marker typically seen in basal cells. Given these conflicting results, we hypothesized that much like basal-like breast carcinomas (BLBCs), these prostate tumors may be arising from a stem cell with a partially retained basal cell immunophenotype. Thus, we examined their expression of additional basal cell, luminal cell and stemness markers.
Design: p63-expressing tumors from 11 radical prostatectomy specimens and 2 needle biopsies were immunostained for luminal cell markers (CK18, androgen receptor, prostein/p501s), additional basal cell markers (CK5/6) and pluripotency/progenitor markers (-catenin, Oct4, c-kit).
Results: All 13 p63-expressing cases showed strong diffuse positivity for CK18, a LMWCK expressed in benign prostatic luminal cells, but not in basal cells. Similarly, 10/10 of evaluable cases also expressed the androgen receptor, with 90% (9/10) of these cases showing strong nuclear staining of equal or greater intensity than surrounding benign luminal cells. In contrast, basal cells in the surrounding benign glands showed only weak, focal positivity for the androgen receptor. 92% (12/13) of evaluable cases strongly expressed prostein (p501s), an additional marker of luminal prostatic epithelial cells. Conversely, basal cytokeratins (CK5/6) were predominantly negative in the p63-expressing tumors, with only 36% (4/11) of evaluable cases showing weak, focal expression in tumor cells at a much lower level than benign basal cells. Pluripotency/pluripotential markers including -catenin, Oct4 and c-kit were uniformly negative in p63-expressing tumors, additional support for their luminal phenotype.
Conclusions: PCa with aberrant p63-expression belong to a small group of human carcinomas expressing p63 with luminal-type cytokeratins. BLBCs show a similar immunophenotype, with expression of p63 and CK8/18, however, unlike p63-expressing prostate adenocarcinomas, BLBCs invariably express HMWCK (CK5/6, 34E12) and are typically negative for hormone receptors (ER/PR). Our results suggest that p63-expressing prostate carcinomas show a predominantly luminal cell immunophenotype and raise the possibility that the p63 transcription factor may be expressed but inactive in these tumors.
Category: Genitourinary (including renal tumors)
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 125, Tuesday Afternoon