title: 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.
authors.affiliation: Pathologic Oncology, Division of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Mie, 5148507, Japan; Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, 21231.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, 21231.
authors.forename: Hillary
authors.initials: H
authors.lastname: Ross
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, 21231.
authors.forename: Tamara
authors.initials: T
authors.lastname: Lotan
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Pignon
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115.
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, 21231.
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, 21231. Electronic address: pillei1@jhmi.edu.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Illei
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001707:Biopsy, Needle; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D020033:Protein Isoforms; D014157:Transcription Factors / Q000032:analysis*; D025521:Tumor Suppressor Proteins / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; C081876:CKAP4 protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
keywords: Adenocarcinoma; Immunohistochemistry; Prostate; p40; p63; ΔNp63