Yokoyama Y, Sato S, Futagami M, Fukushi Y, Sakamoto T, Umemoto M, Saito Y
Department of Obstetrics and Gynecology, Hirosaki University School of Medicine, Hirosaki, 036-8562, Japan.
Gynecol Oncol. 2000 Jun;77(3):413-8. doi: 10.1006/gyno.2000.5802.
The aim of this study has been to evaluate the clinical significance of expression of VEGF and its receptors, Flt-1, KDR, and Flt-4, in endometrial carcinomas.
Specimens of endometrial carcinomas from 86 patients were investigated immunohistochemically using respective specific antibodies. Additionally, samples from 14 patients with complex atypical endometrial hyperplasia (AEH) and 15 patients with normal endometria were also examined. Immunohistochemical assessment was classified as negative, weakly positive, and strongly positive according to staining intensity and the percentage of positive cells.
In positive cases, VEGF and its receptors were usually expressed homogeneously in the cytoplasms of cells in the endometrial carcimona, similar to the staining intensity of endothelial cells of stromal microvessels adjacent to carcinoma nests. The overall positive rates in the 86 carcinoma specimens were 66% for VEGF, 51% for Flt-1, 38% for KDR, and 57% for Flt-4. Their expressions in endometrial carcinoma tissues were high with significance or with borderline significance, compared to those in samples of complex AEH or normal endometria. Survival curves determined by the Kaplan-Meier method and univariate analysis showed VEGF, Flt-1, and Flt-4 overexpression to be related to poor prognosis of patients with endometrial carcinomas. However, multivariate analysis revealed that Flt-4 overexpression correlated independently with poor survival, similar to a value for myometrial invasion at one-half or more and that for retroperitoneal lymph node metastasis, whereas VEGF and Flt-1 overexpression did not.
Flt-4 overexpression might be a promising prognostic indicator for survival of a patient with endometrial carcinoma.
本研究旨在评估血管内皮生长因子(VEGF)及其受体Flt-1、KDR和Flt-4在子宫内膜癌中的表达的临床意义。
采用各自的特异性抗体,对86例子宫内膜癌患者的标本进行免疫组织化学研究。此外,还检测了14例复杂性非典型子宫内膜增生(AEH)患者和15例正常子宫内膜患者的样本。根据染色强度和阳性细胞百分比,免疫组织化学评估分为阴性、弱阳性和强阳性。
在阳性病例中,VEGF及其受体通常在子宫内膜癌细胞的细胞质中均匀表达,类似于癌巢旁间质微血管内皮细胞的染色强度。86例癌标本中,VEGF的总体阳性率为66%,Flt-1为51%,KDR为38%,Flt-4为57%。与复杂性AEH或正常子宫内膜样本相比,它们在子宫内膜癌组织中的表达较高,具有显著意义或临界意义。采用Kaplan-Meier法和单因素分析确定的生存曲线显示,VEGF、Flt-1和Flt-4的过表达与子宫内膜癌患者的不良预后相关。然而,多因素分析显示,Flt-4过表达与生存率低独立相关,类似于肌层浸润达一半或更多以及腹膜后淋巴结转移的情况,而VEGF和Flt-1过表达则不然。
Flt-4过表达可能是子宫内膜癌患者生存的一个有前景的预后指标。