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Yes相关蛋白(YAP)在乳腺叶状肿瘤中的表达

Expression of Yes-associated protein (YAP) in breast phyllodes tumor.

作者信息

Kim Sang Kyum, Jung Woo Hee, Koo Ja Seung

机构信息

Department of Pathology, Yonsei University College of Medicine Seoul, South Korea.

出版信息

Int J Clin Exp Pathol. 2014 Aug 15;7(9):5997-6005. eCollection 2014.

Abstract

This study aimed to identify expression profiles of Yes-associated protein (YAP) and its phosphorylated form (pYAP) in phyllodes tumor (PT) of human breast and verify the clinical implications. We selected PTs from the pathologic archive and reviewed the histologic features (141 benign, 27 borderline, and 15 malignant). We made tissue microarray (TMA) block from the formalin-fixed paraffin-embedded (FFPE) tissue corresponding to the representative section. Using TMA block, we performed immunohistochemical staining of YAP and pYAP. In the stromal component, expressions of YAP and pYAP were increased in borderline/malignant PT with comparison of benign PT (P = 0.002, and P < 0.001, respectively). In the epithelial component, cytoplasmic expression of YAP was highest in borderline PT (P = 0.001). Stromal YAP expression (P < 0.001) and stromal pYAP expression (P = 0.042) were associated with shorter disease-free survival (DFS) and stromal pYAP expression (P = 0.001) was associated with shorter overall survival (OS) in univariate Cox analysis. In multivariate Cox analysis, stromal YAP expression was an independent prognostic factor associated with shorter DFS (Hazard ration: 3.206, 95% CI: 1.000-10.27, P = 0.050). In conclusion, expression level of YAP in stromal component was increased along with histologic grade of PT and YAP expression in PT was related to tumor progression and poor prognosis.

摘要

本研究旨在确定人乳腺叶状肿瘤(PT)中Yes相关蛋白(YAP)及其磷酸化形式(pYAP)的表达谱,并验证其临床意义。我们从病理档案中选取PT病例,并回顾其组织学特征(141例良性、27例交界性和15例恶性)。我们从对应于代表性切片的福尔马林固定石蜡包埋(FFPE)组织制作组织微阵列(TMA)块。使用TMA块,我们对YAP和pYAP进行免疫组织化学染色。在间质成分中,与良性PT相比,YAP和pYAP在交界性/恶性PT中的表达增加(分别为P = 0.002和P < 0.001)。在上皮成分中,YAP的细胞质表达在交界性PT中最高(P = 0.001)。在单变量Cox分析中,间质YAP表达(P < 0.001)和间质pYAP表达(P = 0.042)与无病生存期(DFS)缩短相关,间质pYAP表达(P = 0.001)与总生存期(OS)缩短相关。在多变量Cox分析中,间质YAP表达是与DFS缩短相关的独立预后因素(风险比:3.206,95%可信区间:1.000 - 10.27,P = 0.050)。总之,PT间质成分中YAP的表达水平随PT组织学分级增加而升高,PT中YAP表达与肿瘤进展及预后不良相关。

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