Hedvat Cyrus V, Teruya-Feldstein Julie, Puig Pere, Capodieci Paola, Dudas Maria, Pica Natalie, Qin Jing, Cordon-Cardo Carlos, Di Como Charles J
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Appl Immunohistochem Mol Morphol. 2005 Sep;13(3):237-42. doi: 10.1097/01.pai.0000142160.52670.ce.
The p63 gene, a homolog of the tumor suppressor gene TP53, maps to chromosome 3q27-28, a region frequently displaying genomic amplification in squamous cell carcinomas. p63 is expressed in a variety of epithelial tissues and has been reported to be critical for the normal development of stratified epithelia, including skin epidermis. In a previous study, the authors reported the expression of p63 in occasional cells in the germinal center of lymph nodes and also observed p63 expression in B-cell lymphomas, among other tumor types surveyed in that analysis. The present study was conducted to further analyze the potential clinical significance of identifying p63 expression, assessing a larger cohort of well-characterized patients with diffuse large B-cell lymphoma (DLBCL) (n = 172 cases) and a panel of established lymphoma cell lines. p63 expression at the microanatomic detail was examined by immunohistochemistry using a monoclonal antibody (clone 4A4), while distinction of p63 isoforms was analyzed by Western blotting and reverse transcription-polymerase chain reaction using isoform-specific primers. The authors found that a subset of DLBCL (32% of cases) expressed p63 in the nuclei of neoplastic lymphocytes. Examination of the different p63 isoforms revealed that the DeltaNp63 species was expressed by only one cell line, while the other p63 isoforms were found in most cell lines analyzed. The authors also observed that p63 expression correlated with high proliferative index, as assessed by Ki-67 immunostaining. Even though in univariate analysis p63 expression did not correlate with overall survival, the association of p63 with increased proliferative index suggests its involvement in DLBCL tumor progression.
p63基因是肿瘤抑制基因TP53的同源物,定位于染色体3q27 - 28,该区域在鳞状细胞癌中常出现基因组扩增。p63在多种上皮组织中表达,据报道对包括皮肤表皮在内的复层上皮的正常发育至关重要。在先前的一项研究中,作者报道了p63在淋巴结生发中心的偶见细胞中表达,并且在该分析中调查的其他肿瘤类型中,也在B细胞淋巴瘤中观察到p63表达。本研究旨在进一步分析鉴定p63表达的潜在临床意义,评估一大群特征明确的弥漫性大B细胞淋巴瘤(DLBCL)患者(n = 172例)以及一组已建立的淋巴瘤细胞系。使用单克隆抗体(克隆4A4)通过免疫组织化学检查微观解剖细节处的p63表达,同时使用亚型特异性引物通过蛋白质免疫印迹和逆转录 - 聚合酶链反应分析p63亚型的区分。作者发现一部分DLBCL(32%的病例)在肿瘤淋巴细胞的细胞核中表达p63。对不同p63亚型的检查显示,DeltaNp63亚型仅在一种细胞系中表达,而在大多数分析的细胞系中发现了其他p63亚型。作者还观察到,如通过Ki - 67免疫染色评估,p63表达与高增殖指数相关。尽管在单变量分析中p63表达与总生存期无关,但p63与增殖指数增加的关联表明其参与了DLBCL肿瘤进展。