VEGF, flt-1, and KDR/flk-1 as prognostic indicators in endometrial carcinoma
VEGF, flt-1, and KDR/flk-1 as prognostic indicators in endometrial carcinoma
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DOI：
10.1006/gyno.1999.5658
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发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Dey, T
中科院分区：
文献类型：
--
作者：
Fine, BA;Valente, PT;Dey, T
目标。肿瘤血管生成是一个受宿主微环境和介质高度调控的过程。对乳腺癌的研究以及最近对卵巢癌和宫颈癌的研究表明，新生血管与转移和复发的可能性有关。血管内皮生长因子（VEGF）是子宫内膜肿瘤血管生成的重要调节因子，flt-1和KDR/flk-1是很好的血管增殖标志物。由于血管生成是疾病进展的先兆，我们假设量化子宫恶性肿瘤中VEGF、flt-1和KDR/flk-1的表达比肿瘤的FIGO分级、浸润深度和组织学更能预测转移潜力和生存。本文回顾了47例子宫恶性肿瘤（腺癌35例，乳头状浆液性6例，癌肉瘤6例）的病理切片。获得原发肿瘤的石蜡块。对VEGF、flt-1和KDR/flk-1进行免疫组化染色。用于分析VEGF和受体浓度的微血管密度由两名独立研究者测定，他们对患者的临床状态不知情。分别采用logistic回归分析和产品极限生命系统生存分析来确定VEGF、flt-1和KDR/flk-1以及分期、分级、浸润深度和淋巴结状态对转移发生率、复发和生存的影响。结果表明，在评估所有三种组织学类型时，仅发现肿瘤分期和分级对复发率和生存率有影响。当癌肉瘤和乳头状浆液腺癌患者被排除在分析之外时，肿瘤的分期和分级仍然是复发和生存的重要预后指标。只有肿瘤分级和子宫浸润深度是肿瘤转移潜力的重要预测因子。VEGF、flt-1和KDR/flk-1在预测转移、复发和生存方面的意义不大。所有三种组织学亚型的晚期患者通常VEGF和受体阳性水平较低。在本研究中，VEGF、flt-1和KDR/flk-1受体浓度与转移、复发和生存的发生率无关。(C) 2000年学术出版社。
Objective. Tumor angiogenesis is a highly regulated process under the influence of the host microenvironment and mediators. Studies of breast cancer and, more recently, ovarian and cervical cancer, demonstrate that neovascularization correlates with the likelihood of metastasis and recurrence. Vascular endothelial growth factor (VEGF), an important regulator of tumor angiogenesis in the endometrium, flt-1, and KDR/flk-1 are good markers of vascular proliferation. Being that angiogenesis is a precursor to the development of progressive disease, we hypothesize that quantifying VEGF, flt-1, and KDR/flk-1 expression in uterine malignancies is a superior predictor of metastatic potential and survival than is FIGO grade of tumor, depth of invasion, and histology.Methods. The histologic slides of 47 patients with uterine malignancies (35 adenocarcinomas, 6 papillary serous, and 6 carcinosarcomas) were reviewed. The paraffin blocks from the primary tumor were obtained. Immunohistochemistry staining was performed for VEGF, flt-1, and KDR/flk-1. Microvessel density, used to analyze VEGF and receptor concentrations, was determined by two independent investigators, who were blinded to the patients clinical status. The impact of VEGF, flt-1, and KDR/flk-1 as well as stage, grade, depth of invasion, and nodal status on the incidence of metastases, recurrence, and survival was determined using logistic regression analysis and product limit life system survival analysis, respectively.Results. Results indicated that when evaluating all three histologic types, only stage and grade of tumor were found to impact upon the incidence of recurrence and survival. When patients with carcinosarcoma and papillary serous adenocarcinoma were excluded from the analysis, once again only stage and grade of tumor were significant prognostic indicators of recurrence and survival. Only grade of tumor and depth of uterine invasion were significant predictors of a tumor's metastatic potential. VEGF, flt-1, and KDR/flk-1 proved to be of little significance in predicting metastases, recurrence, and survival. Patients with advanced disease in all three histologic subtypes often had low VEGF and receptor positivity.Conclusions. In this study, VEGF, flt-1, and KDR/flk-1 receptor concentrations did not correlate with the incidence of metastases, recurrence, and survival. (C) 2000 Academic Press.