Mylona E, Alexandrou P, Mpakali A, Giannopoulou I, Liapis G, Markaki S, Keramopoulos A, Nakopoulou L
Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece.
Eur J Surg Oncol. 2007 Apr;33(3):294-300. doi: 10.1016/j.ejso.2006.10.015. Epub 2006 Nov 28.
Vascular endothelial growth factors C and D (VEGF-C and VEGF-D) play a major role in lymphangiogenesis and activate VEGF receptor 3 (VEGFR-3). Our purpose was to study the clinicopathologic and clinical value of VEGF-C, VEGF-D and VEGFR-3 in invasive breast carcinoma.
Immunohistochemistry was performed in paraffin-embedded tissue specimens from 177 invasive breast carcinomas to detect the proteins VEGF-C, VEGF-D, VEGFR-3, p53, Ki67, c-erbB-2, topoII alpha and ER/PR. The results were statistically processed.
VEGF-C, VEGF-D and VEGFR-3 were found to be predominantly expressed in the cytoplasm of the malignant cells. VEGF-C occasionally showed a submembranous intensification. VEGF-D and VEGFR-3 were also immunodetected in the nuclei of the malignant cells. Nuclear VEGF-D was positively correlated to p53, Ki67 and topoII alpha proteins' expression (p=0.003, p=0.009 and p=0.017 respectively) and nuclear VEGFR-3 to topoII alpha (p=0.034). Cytoplasmic expression of VEGF-C and its submembranous intensification were found to be independent indicators of patients' overall and disease-free survival, respectively (p=0.003 and p=0.044 respectively). The group with high expression of both cytoplasmic VEGF-C and stromal VEGFR-3 showed poor overall survival (p=0.024) and the group with both submembranous VEGF-C and stromal VEGFR-3 immunostaining showed poor both disease-free and overall survival (p=0.012 and p=0.038 respectively).
VEGF-D and VEGFR-3 seem to exert proliferative activity in invasive breast carcinomas. VEGF-C was found to be an independent indicator of patient's poor prognosis and the simultaneous expression of tumor VEGF-C and stromal VEGFR-3 yielded additional prognostic information.
血管内皮生长因子C和D（VEGF-C和VEGF-D）在淋巴管生成中起主要作用，并激活血管内皮生长因子受体3（VEGFR-3）。我们的目的是研究VEGF-C、VEGF-D和VEGFR-3在浸润性乳腺癌中的临床病理及临床价值。
对177例浸润性乳腺癌石蜡包埋组织标本进行免疫组织化学检测，以检测VEGF-C、VEGF-D、VEGFR-3、p53、Ki67、c-erbB-2、拓扑异构酶IIα和雌激素受体/孕激素受体（ER/PR）蛋白。对结果进行统计学处理。
发现VEGF-C、VEGF-D和VEGFR-3主要在恶性细胞的细胞质中表达。VEGF-C偶尔表现为膜下强化。VEGF-D和VEGFR-3也在恶性细胞核中被免疫检测到。细胞核VEGF-D与p53、Ki67和拓扑异构酶IIα蛋白的表达呈正相关（分别为p = 0.003、p = 0.009和p = 0.017），细胞核VEGFR-3与拓扑异构酶IIα呈正相关（p = 0.034）。发现VEGF-C的细胞质表达及其膜下强化分别是患者总生存期和无病生存期的独立指标（分别为p = 0.003和p = 0.
