Lymphatic Vessel Density and Lymphangiogenesis in Human Oral Squamous Cell Carcinoma

S. Yoshida, T. Aida, T. Tachikawa
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Abstract

Lymphatic vessels are distributed directly under the epithelium of the oral mucosal. In the present study, we investigated whether lymphoangiogenseis in tumors occurs in human oral squamous cell carcinoma and whether the density of tumor lympahngiogensis may be related to the risk of lymph node metastasis. Moreover, these analyses identified peritumoral lymphatic vascular density as a novel prognostic indicator for the risk of lymph node metastasis in oral squamous cell carcinoma. LYVE-1, which was an endothelial cell hyaluronic acid receptor, has been identified as a peculiar protein of endothelial cells of lymphatic vessels. LYVE-1 expression in the carcinoma tissue was divided into two types. In one it appears in contact with the cancer nest. This shows contact with basal-like cells which are located on the outer side of the cancer nest, and observation via light microscope is unable to show intervention of the fibrous connective tissues. The other case is that in which there is intervention of the clear fibrous connective tissues between the cancer nest and LYVE-1-positive cells. The cancer cells showed a high degree of differentiation, increased by the formation of the cancer nest, and in what is called highly-differentiated squamous cell carcinoma whose invasion pattern showed INF alpha, the cells staining positive to the LYVE-1 antibody could be recognized only negligibly in the connective tissue. Positive staining of the LYVE-1 antibody was seen in the endothelial cells presenting in the lumen formed between each small cancer nest in the case of undifferentiated squamous cell carcinoma in which the cancer nest was very small and composed of undifferentiated cancer cells. In this case the cancer invasion pattern shows INFy. In addition, the expression of LYVE-1 was recognized in cells which had not formed into the lumen between the cancer nests. In the meantime, VEGF-C was expressed in endothelial cells which formed the lumen and cancer cells. In the cancer cells which formed the large cancer nest, the expression of VEGF-C was recognized in basal-like cells which located at the periphery of the nest. VEGF-C was expressed in the cancer cells which formed the small nest. The results of this study show that the incidence of VEGF-C expression in the cancer cell is low. However, lymphatic vessels form in carcinoma tissue at a high rate when VEGF-C is expressed. It was shown that in this study, the close proximity of the lymphatic vessel to the cancer nest shows correlation to lymph node metastasis. This should affect the determination of the operation range, and have a direct influence on prognosis. It is also indicated that LYVE-1 can act as a useful marker in oral cancer.
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人口腔鳞状细胞癌的淋巴管密度和淋巴管生成
淋巴管直接分布在口腔粘膜上皮下。在本研究中,我们研究了人类口腔鳞状细胞癌肿瘤中是否发生淋巴血管增生,以及肿瘤淋巴增生的密度是否与淋巴结转移的风险有关。此外,这些分析表明,瘤周淋巴血管密度是口腔鳞状细胞癌淋巴结转移风险的一个新的预后指标。LYVE-1是一种内皮细胞透明质酸受体,是淋巴管内皮细胞特有的蛋白。LYVE-1在癌组织中的表达分为两种类型。在一种情况下,它似乎与癌巢接触。图示与癌巢外侧的基底样细胞接触,光镜下观察无法显示纤维结缔组织的介入。另一种情况是癌巢与lyve -1阳性细胞之间的透明纤维结缔组织有干预。癌细胞表现出高度分化,随着癌巢的形成而增加,在侵袭模式为INF α的所谓高分化鳞状细胞癌中,LYVE-1抗体染色阳性的细胞仅在结缔组织中可以忽略不计。未分化鳞状细胞癌的癌巢非常小,由未分化的癌细胞组成,在每个小癌巢之间形成的管腔内内皮细胞可见LYVE-1抗体阳性染色。本例肿瘤侵袭模式为INFy。此外,LYVE-1在癌巢间未形成管腔的细胞中也有表达。同时,VEGF-C在形成管腔和癌细胞的内皮细胞中表达。在形成大癌巢的癌细胞中,位于癌巢外围的基底样细胞中可识别VEGF-C的表达。VEGF-C在形成小巢的癌细胞中表达。本研究结果表明,VEGF-C在癌细胞中的表达发生率较低。然而,当VEGF-C表达时,淋巴管在癌组织中的形成率很高。本研究显示,淋巴管离癌巢较近,与淋巴结转移有关。这应影响手术范围的确定,并对预后有直接影响。LYVE-1可作为口腔癌的有效标志物。
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