Bilodeau Elizabeth A, Acquafondata Marie, Barnes E Leon, Seethala Raja R
Department of Diagnostic Sciences, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA 15261.
Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213.
Hum Pathol. 2015 Feb;46(2):255-9. doi: 10.1016/j.humpath.2014.10.018. Epub 2014 Nov 12.
LEF-1 is a nuclear transcription factor of the Wnt pathway that regulates multipotent skin stem cell differentiation. β-Catenin is considered a transcriptional coactivator that interacts with LEF-1.This study evaluates LEF-1 in a variety of odontogenic and salivary tumors and determines the prevalence of β-catenin coexpression. Ninety-eight salivary gland tumors and 51 odontogenic tumors were evaluated for LEF-1 and β-catenin immunohistochemical staining. Positivity was defined as at least 2+ intensity in more than 50% of tumor cells, which required a composite score of 6 or more. LEF-1 was positive in 64% (7/11) of calcifying cystic odontogenic tumors (CCOT). Nuclear β-catenin was present in 82% (9/11) of CCOT. Coexpression of LEF-1 and nuclear β-catenin was noted in all LEF-1-positive CCOT. Strong and diffuse LEF-1 expression was seen in 69% (11/16) of basal cell adenocarcinomas (BCAC) and 63% (5/8) of basal cell adenomas (BA). Nuclear β-catenin was present in 50% (4/8) of BA and 43% (6/14) of BCAC. For BA, 4 of 5 LEF-1-positive tumors showed coexpression of β-catenin, and for BCAC, 5 of 9 LEF-1-positive tumors showed coexpression. In conclusion, this study documents for the first time the presence of LEF-1 expression and nuclear β-catenin coexpression in select basaloid salivary gland tumors and various odontogenic tumors. We demonstrate LEF-1 expression in both BA and BCAC preferentially over other salivary gland tumors suggesting some utility as a diagnostic marker.
LEF-1是Wnt信号通路的一种核转录因子,可调节多能皮肤干细胞的分化。β-连环蛋白被认为是一种与LEF-1相互作用的转录共激活因子。本研究评估了LEF-1在多种牙源性肿瘤和涎腺肿瘤中的表达情况,并确定了β-连环蛋白共表达的发生率。对98例涎腺肿瘤和51例牙源性肿瘤进行了LEF-1和β-连环蛋白免疫组织化学染色评估。阳性定义为超过50%的肿瘤细胞中强度至少为2+,这需要综合评分6分或更高。在64%(7/11)的钙化囊性牙源性肿瘤(CCOT)中LEF-1呈阳性。82%(9/11)的CCOT中存在核β-连环蛋白。在所有LEF-1阳性的CCOT中均观察到LEF-1与核β-连环蛋白的共表达。在69%(11/16)的基底细胞腺癌(BCAC)和63%(5/8)的基底细胞腺瘤(BA)中可见LEF-1强而弥漫性表达。50%(4/8)的BA和43%(6/14)的BCAC中存在核β-连环蛋白。对于BA,5例LEF-1阳性肿瘤中有4例显示β-连环蛋白共表达,对于BCAC,9例LEF-1阳性肿瘤中有5例显示共表达。总之,本研究首次记录了在特定的基底样涎腺肿瘤和各种牙源性肿瘤中存在LEF-1表达和核β-连环蛋白共表达。我们证明,与其他涎腺肿瘤相比,BA和BCAC中LEF-1表达更具优势,提示其作为诊断标志物具有一定实用性。