ΔNp63 (p40) expression in prostatic adenocarcinoma with diffuse p63 positivity

Abstract

Basal cells of benign prostate glands are typically p63 positive, whereas malignant glands are usually p63 negative. A rare subset of prostatic adenocarcinoma (PCa) demonstrates aberrant diffuse p63 expression but is negative for high-molecular-weight cytokeratin. Strong p63 staining of the tumor cells can obscure the loss of high-molecular-weight cytokeratin when using a cocktail of basal cell markers and create a diagnostic pitfall. The p63 protein has 6 major isoforms; of these, TAp63 and ΔNp63 (p40) are the best characterized N-terminal variants. In an attempt to aid in the diagnosis of p63-positive PCas, we studied ΔNp63 expression in tumors with aberrant p63. Immunohistochemistry was performed on 31 cores of aberrant p63-positive PCas from 24 patients and on a tissue microarray containing 125 cores of conventional PCas from 40 radical prostatectomy cases using a ΔNp63-specific polyclonal (p40) antibody and a TAp63-specific monoclonal antibody (p63, clone 4A4) that recognizes both TAp63 and ΔNp63. Most of the aberrant p63-positive tumors showed diffuse positivity for p40 (29/31 cores, 93.5%; 23/24 cases, 96%). All 40 conventional PCa (125 cores) were negative for p40 and p63 in the tumor cells. In summary, p40 is expressed in most p63-positive PCas but negative in p63-negative conventional PCas. From a diagnostic perspective, the use of immunohistochemistry for ΔNp63/p40 provides only a small advantage over the more widely used p63 assays. Our 1 ΔNp63-negative p63-positive case may represent expression of the TAp63 isoform in the tumor.

Keywords: Adenocarcinoma; Immunohistochemistry; Prostate; p40; p63; ΔNp63.