DeltaNp63 Isoforms of p63 in Aberrant Diffuse p63 Positive Prostate Cancer
Katsunori Uchida, Hillary M Ross, Jonathan I Epstein, Tamara Lotan, Peter B Illei. The Johns Hopkins Hospital, Baltimore
Background: p63 typically labels prostatic basal cells in benign glands and is negative in adenocarcinoma of the prostate. Prostatic adenocarcinoma with aberrant diffuse p63 expression is extremely rare and poorly understood. The only series of this entity is of 21 cases compiled from a busy consult service. On H&E-stained slides, the tumor typically shows a distinctive morphology composed predominantly of glands, nests, and cords with atrophic cytoplasm, hyperchromatic nuclei, and visible nucleoli. Although the lesion does not express high molecular weight cytokeratin (HMWCK), p63 staining in the tumor with use of a PIN4 cocktail can obscure the loss of HMWCK and may be a diagnostic pitfall. The p63 protein is present in at least 6 major isoforms. Of these, TAp63 and deltaNp63 are the best characterized N-terminal variants, with deltaNp63 mRNA expressed at more than 100-fold higher levels than TAp63 in the normal prostate. While the p63 antibody recognizes both protein variants, a recently available p40 antibody only recognizes deltaNp63. In an attempt to aid in the diagnosis of p63 positive adenocarcinomas, we studied the p40 antibody to see if it was a more specific marker that does not show aberrant positivity.
Design: Immunohistochemistry for p40 was performed on 23 cores with aberrant p63 positive prostate adenocarcinoma from 16 patients. In all cases, parallel sections were additionally stained with p63 to confirm that the cancer present on deeper sections aberrantly expressed p63.
Results: 15/16 cases (94%) consisting of 21/23 cores showed diffuse expression of both p40 and p63 in the prostate adenocarcinomas. One case (two cores) was positive for p63 but entirely negative for p40. This case was morphologically identical to the other 15 cases. The basal cells in adjacent benign prostate glands in all cases stained uniformly for both p63 and p40, which were both negative in the overlying secretory cells.
Conclusions: DeltaNp63, as detected by the p40 antibody, is expressed in the majority of p63 positive prostate adenocarcinomas. This is consistent with the partial basal-like immunophenotype of these unusual tumors. From a diagnostic perspective, the use of the p40 antibody provides only a small advantage over the currently in use p63 antibody. Our one p40 negative p63 positive case may represent expression of the TAp63 isoform in the tumor. We are also currently further characterizing these tumors by looking at other basal/stem/progenitor cell markers.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 1:00 PM
Poster Session II # 189, Monday Afternoon