Livasy Chad A, Moore Dominic, Cance William G, Lininger Ruth A
Department of Pathology, University of North Carolina, Chapel Hill, NC 27599-7525, USA.
Appl Immunohistochem Mol Morphol. 2004 Dec;12(4):342-5. doi: 10.1097/00129039-200412000-00009.
Focal adhesion kinase (FAK) is a protein tyrosine kinase that is a critical mediator of signaling events between cells and their extracellular matrix. Elevations in FAK mRNA and protein overexpression have been linked to tumor cell capacity for invasion and metastasis. FAK expression has been shown to be elevated in a variety of solid tumors. The purpose of this study was to evaluate for FAK upregulation in endometrial neoplasia. Tissue microarray blocks were made from formalin-fixed, paraffin-embedded archival tissue, including 115 carcinoma (100 endometrioid, 10 serous, and 5 clear cell), 28 hyperplasia, and 38 normal specimens using 1-mm punches. The tissue was immunostained with monoclonal antibody for FAK and p53. Immunoreactivity was scored by intensity (0-4+ scale) and percent positive staining. FAK overexpression was categorized as 4+ cytoplasmic intensity in more than 90% of neoplastic cells. Positive p53 was categorized at least 2+ nuclear intensity in more than 10% of neoplastic cells. Higher rates of FAK upregulation were identified in endometrial hyperplasia (P = 0.025) and carcinoma (P < 0.001) versus normal endometrium. FAK overexpression in carcinoma correlated with higher FIGO grade (P = 0.025) and p53 overexpression (P < 0.001). FAK was consistently overexpressed in high-grade tumors regardless of subtype, including 8 of 10 serous tumors, 4 of 5 clear cell tumors, and 16 of 23 grade 3 endometrioid tumors. In conclusion, upregulation of FAK is seen in both endometrial hyperplasia and carcinoma, implying that FAK may play an important role in endometrial carcinogenesis. FAK overexpression in endometrial carcinoma correlates with higher FIGO grade and p53 overexpression.
黏着斑激酶（FAK）是一种蛋白质酪氨酸激酶，是细胞与其细胞外基质之间信号转导事件的关键介质。FAK mRNA和蛋白质的过度表达升高与肿瘤细胞的侵袭和转移能力有关。已证明FAK表达在多种实体瘤中升高。本研究的目的是评估子宫内膜肿瘤中FAK的上调情况。组织微阵列块由福尔马林固定、石蜡包埋的存档组织制成，包括115例癌（100例子宫内膜样癌、10例浆液性癌和5例透明细胞癌）、28例增生和38例正常标本，使用1毫米打孔器获取组织。用针对FAK和p53的单克隆抗体对组织进行免疫染色。通过强度（0 - 4 +级）和阳性染色百分比对免疫反应性进行评分。FAK过表达被分类为超过90%的肿瘤细胞中细胞质强度为4 +。p53阳性被分类为超过10%的肿瘤细胞中核强度至少为2 +。与正常子宫内膜相比，子宫内膜增生（P = 0.025）和癌（P < 0.001）中FAK上调率更高。癌中FAK过表达与更高的国际妇产科联盟（FIGO）分级（P = 0.025）和p53过表达（P < 0.001）相关。无论亚型如何，FAK在高级别肿瘤中始终过度表达，包括10例浆液性肿瘤中的8例、5例透明细胞肿瘤中的4例和23例3级子宫内膜样肿瘤中的16例。总之，在子宫内膜增生和癌中均可见FAK上调，这意味着FAK可能在子宫内膜癌发生中起重要作用。子宫内膜癌中FAK过表达与更高的FIGO分级和p53过表达相关。
