Uchida Katsunori, Ross Hillary, Lotan Tamara, Pignon Jean-Christophe, Signoretti Sabina, Epstein Jonathan I, Illei Peter B
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.
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, 21231.
Hum Pathol. 2015 Mar;46(3):384-9. doi: 10.1016/j.humpath.2014.11.011. Epub 2014 Dec 2.
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.
良性前列腺腺泡的基底细胞通常p63呈阳性，而恶性腺泡通常p63呈阴性。前列腺腺癌（PCa）的一个罕见亚群表现出异常的弥漫性p63表达，但高分子量细胞角蛋白呈阴性。当使用基底细胞标志物组合时，肿瘤细胞的强p63染色可能会掩盖高分子量细胞角蛋白的缺失，从而造成诊断陷阱。p63蛋白有6种主要异构体；其中，TAp63和ΔNp63（p40）是特征最明确的N端变体。为了辅助诊断p63阳性的PCa，我们研究了异常p63肿瘤中ΔNp63的表达。使用ΔNp63特异性多克隆（p40）抗体和识别TAp63和ΔNp63的TAp63特异性单克隆抗体（p63，克隆4A4），对24例患者的31个异常p63阳性PCa核心组织以及包含40例根治性前列腺切除病例的125个常规PCa核心组织的组织芯片进行免疫组织化学检测。大多数异常p63阳性肿瘤p40呈弥漫性阳性（29/31个核心组织，93.5%；23/24例，96%）。所有40例常规PCa（125个核心组织）肿瘤细胞中p40和p63均为阴性。总之，p40在大多数p63阳性的PCa中表达，但在p63阴性的常规PCa中为阴性。从诊断角度来看，与更广泛使用的p63检测相比，使用免疫组织化学检测ΔNp63/p40仅具有微小优势。我们的1例ΔNp63阴性p63阳性病例可能代表肿瘤中TAp63异构体的表达。
