EphA2 overexpression is associated with lack of hormone receptor expression and poor outcome in endometrial cancer.
EphA2 overexpression is associated with lack of hormone receptor expression and poor outcome in endometrial cancer.
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作者：
Kamat AA;Coffey D;Merritt WM;Nugent E;Urbauer D;Lin YG;Edwards C;Broaddus R;Coleman RL;Sood AK
EphA 2是肝配蛋白家族中的酪氨酸激酶受体，其涉及肿瘤发生和血管生成。我们的目标是研究EphA 2在子宫内膜癌中的作用及其与类固醇激素受体表达的关系。应用免疫组化方法检测139例子宫内膜样癌（EEC）和10例良性子宫内膜组织中EphA 2、雌激素受体（ER）、孕激素受体（PR）和Ki-67的表达。由2名对临床结果不知情的研究者对样本进行评分。结果与临床病理特征进行单因素和多因素分析。p值<0.05被认为具有统计学显著性。在48%的EEC样品中检测到EphA 2的高表达，而良性样品中为10%。EphA 2过表达与高分期（p=0.04）、高分级（p=0.003）、子宫肌层浸润深度增加（p=0.05）、低ER（p=0.01）、低PR（p=0.006）和高Ki-67表达（p=0.04）显著相关。ER和PR低表达均与高级别、阳性淋巴结、Ki-67高表达和EphA 2高表达相关。在所有患者的单变量分析中，高EphA 2表达与较短的疾病特异性存活显著相关（DSS，p<0.001）。在多变量分析中，年龄（p<0.001）、高分期（p=0.002）和高EphA 2表达（p=0.04）是不良DSS的独立预测因子。EphA 2过表达与子宫内膜样癌的侵袭性表型特征相关，并与ER和PR表达呈负相关。因此，EphA 2可能是一个重要的治疗靶点，特别是在EphA 2受体阴性的子宫内膜癌患者中。
EphA2 is a tyrosine kinase receptor in the ephrin family that is implicated in oncogenesis and angiogenesis. Our goal was to study the role of EphA2 in endometrial cancer and its relation to steroid hormone receptor expression. EphA2, estrogen receptor (ER), progesterone receptor (PR) and Ki-67 expression were evaluated using immunohistochemistry in 139 endometrioid endometrial carcinomas (EEC) and in 10 benign endometrial samples. Samples were scored by 2 investigators blinded to clinical outcome. Results were correlated with clinicopathologic characteristics using univariate and multivariate analysis. A p value of <0.05 was considered statistically significant. High expression of EphA2 was detected in 48% of EEC samples vs. 10% of benign samples. EphA2 overexpression was significantly associated with high-stage (p=0.04), high-grade (p=0.003), increased depth of myometrial invasion (p=0.05), low ER (p=0.01), low PR (p=0.006) and high Ki-67 expression (p=0.04). Low ER and PR expression were both associated with high-grade, positive lymph nodes, high Ki-67 expression and high EphA2 expression. On univariate analysis of all patients, high EphA2 expression was significantly associated with shorter disease-specific survival (DSS, p<0.001). On multivariate analysis, age (p<0.001), high-stage (p=0.002) and high EphA2 expression (p=0.04) were independent predictors of poor DSS. EphA2 overexpression is associated with aggressive phenotypic features in endometrioid endometrial carcinomas, and is inversely associated with ER and PR expression. Thus, EphA2 may be an important therapeutic target, especially in patients with hormone-receptor negative endometrial carcinoma.
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影响因子：
4.7
作者：
MORRIS, PC;ANDERSON, JR;BULLER, RE
通讯作者：
BULLER, RE
影响因子：
3.3
作者：
SHERMAN, ME;BUR, ME;KURMAN, RJ
通讯作者：
KURMAN, RJ
影响因子：
11.5
作者：
Thaker, PH;Deavers, M;Sood, AK
通讯作者：
Sood, AK
影响因子：
11.5
作者：
Kamat, AA;Fletcher, M;Sood, AK
通讯作者：
Sood, AK
影响因子：
5.3
作者：
LINDBERG, RA;HUNTER, T
通讯作者：
HUNTER, T