Podoplanin、β-catenin及血管内皮生长因子受体3在食管鳞状细胞癌组织中的表达及意义

Expression and significance of podoplanin,β-catenin and vascular endothelial growth factor receptor-3 in tissue of esophageal squamous cell carcinoma

目的观察Podoplanin、β-catenin及血管内皮生长因子受体3(VEGFR-3)在人食管鳞状细胞癌(简称食管鳞癌)组织及癌周边区正常食管组织淋巴管的表达,寻找可用于食管鳞癌组织淋巴管研究的标记物。方法取食管鳞癌患者手术切除组织63份,癌周正常食管组织20份。用免疫组化法检测食管癌组织及癌周边区Podoplanin、β-catenin及VEGFR-3的表达情况。区分有淋巴结转移和无淋巴结转移的食管癌组织标本,比较VEGFR-3表达阳性率的差异。选取正常食管组织和食管癌组织中微脉管丰富的区域,在镜下(×200)计数Podoplanin标记为阳性的淋巴管数量,计算微淋巴管密度(LMVD)。结果结合镜下淋巴管和血管的典型形态学特征,可以确定Podoplanin(阳性表达呈棕黄色间断线状)只表达于淋巴管和毛细淋巴管内皮细胞膜上。VEGFR-3呈棕黄色表达于淋巴管内皮细胞上,在癌细胞胞质和血管壁也可呈阳性表达;VEGFR-3在有淋巴结转移的食管癌标本中淋巴管的表达阳性率明显高于无淋巴结转移标本(分别为68.57%、28.00%,P<0.001)。β-catenin在正常食管及食管癌组织的淋巴管均可呈阳性表达(棕褐色、均匀的线状染色),但在癌组织淋巴管的表达(47.62%)显著高于正常组织和(20.00%,P<0.05)。正常食管组织LMVD(1.46±0.47)明显低于食管癌组织(4.29±1.05,P<0.01)。结论Podoplanin可作为食管癌组织内淋巴管的特异性标记物,VEGFR-3和β-catenin可作为非特异性标记物。VEGFR-3在淋巴管的表达与淋巴结转移密切相关。

Objective To investigate the expression of podoplanin, β-eatenin and vascular endothelial growth factor receptor-3 （VEGFR 3） in lymphatic vessels of human esophageal squamous cell carcinoma （ESCC） tissue and the normal tissues adjacent to the carci noma, and explore the markers which can specifically show the lymphatics with metastasis. Methods 63 surgical specimens of esophageal squamous cell carcinoma and 20 normal tissue specimens were obtained and examined. Immunohisochemical measures were employed to de tect the expressions of podoplanin, β-catenin and VEGFR 3. The difference in expression of VEGFR-3 between ESCC tissue with lymphatic metastasis and the tissue without metastasis was statistically assessed. The lymphatic microvessel density （LMVD） positively stained by podoplanin was observed and counted under microscope with × 200 magnification. Results Based on the morphological characters of lym phatic vessels and capillary vessels observed under microscope, it was confirmed that podoplanin （positively stained as yellow-brownish dis- continuous lines） expressed only on the cellular membrane of endothelial cells of lymphatic and mierolymphatic vessels. VEGFR 3 was pos- itively expressed in the endothelial cells of lymphatic vessels as well as vessel wall and the cytoplasm of carcinoma cell. There existed a sig nificant difference in VEGFR 3 expression between the ESCC tissue with lymphatic metastasis and the tissue without metastasis, and the positive rate was 68. 57% and 28. 00%, respectively （P〈0. 001）. While the expression of l：gcatenin was positive in both normal esophagus tissue and the esophageal carcinoma tissue （positively stained as brownish uniform line）, and the positive rate of the latter （47. 62%） was remarkably higher than that of the former （20. 00%, P〈0. 05）. The LMVD of the normal tissue （1.46±0. 47） was significantly lower than that of the esophageal carcinoma tissue （4.29± 1.05, P〈0. 01）. Conclusions Podoplanin may serve as the specific marker of the lymphatic vessels in esophageal carcinoma, and VEGFR 3 and β-catenin may serve as the non-specific markers. The expression of VEGFR- 3 in lymphatic vessels is closely related with metastasis.