Niki T, Iba S, Yamada T, Matsuno Y, Enholm B, Hirohashi S
Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
J Pathol. 2001 Apr;193(4):450-7. doi: 10.1002/path.828.
Vascular endothelial growth factor receptor 3 (VEGFR-3) has been proposed as a marker for lymphatic endothelial cells. This study investigated the expression of VEGFR-3 in the tumour vessels of lung adenocarcinoma and evaluated whether VEGFR-3 staining was useful for identifying lymphatic vessels within the tumour stroma. It also explored whether active growth of lymphatic vessels occurred in lung adenocarcinoma. Formalin-fixed, paraffin-embedded specimens obtained from 60 cases of lung adenocarcinoma, including five cases of pure bronchiolo-alveolar carcinoma (BAC) without stromal, vascular, and pleural invasion, were examined. No VEGFR-3-positive vessels were observed in pure BAC, but varying numbers of VEGFR-3-positive vessels were found in 39 of 55 (70.9%) invasive adenocarcinomas. A comparison of serial sections stained for VEGFR-3, CD31, and laminin-1 showed that most of the VEGFR-3-positive vessels appeared to be blood vessels (CD31-positive, laminin-1-positive), but some had the characteristics of lymphatic vessels (variable staining for CD31, little or no staining for laminin-1). VEGFR-3 staining highlighted lymphatic invasion by cancer cells; this invasion could not be detected by CD31 or haematoxylin and eosin (H&E) staining. Active growth of lymphatic vessels (as indicated by nuclear Ki-67 labelling of the endothelium) was observed in five tumours, four of which showed a high level of lymphatic invasion by cancer cells. It was concluded that VEGFR-3 immunostaining did not discriminate clearly between vascular and lymphatic endothelial cells, since expression of VEGFR-3 can be up-regulated in tumour blood vessels. However, VEGFR-3 staining combined with laminin-1 and CD31 staining would be useful for identifying lymphatic vessels and their invasion by tumour cells in a more objective way. Finally, proliferation of lymphatic endothelial cells may occur in association with lymphatic invasion by cancer cells.
血管内皮生长因子受体3（VEGFR-3）已被提议作为淋巴管内皮细胞的标志物。本研究调查了VEGFR-3在肺腺癌肿瘤血管中的表达，并评估VEGFR-3染色是否有助于识别肿瘤基质内的淋巴管。研究还探讨了肺腺癌中淋巴管是否存在活跃生长。对60例肺腺癌福尔马林固定、石蜡包埋标本进行了检查，其中包括5例无基质、血管和胸膜侵犯的纯细支气管肺泡癌（BAC）。在纯BAC中未观察到VEGFR-3阳性血管，但在55例浸润性腺癌中的39例（70.9%）发现了数量不等的VEGFR-3阳性血管。对VEGFR-3、CD31和层粘连蛋白-1染色的连续切片进行比较显示，大多数VEGFR-3阳性血管似乎是血管（CD31阳性、层粘连蛋白-1阳性），但有些具有淋巴管的特征（CD31染色可变、层粘连蛋白-1染色很少或无染色）。VEGFR-3染色突出了癌细胞的淋巴浸润；CD31或苏木精和伊红（H&E）染色无法检测到这种浸润。在5个肿瘤中观察到淋巴管活跃生长（以内皮细胞核Ki-67标记为指标），其中4个显示癌细胞有高水平的淋巴浸润。研究得出结论，由于VEGFR-3在肿瘤血管中表达可上调，VEGFR-3免疫染色不能清晰区分血管内皮细胞和淋巴管内皮细胞。然而，VEGFR-3染色联合层粘连蛋白-1和CD31染色将有助于更客观地识别淋巴管及其被肿瘤细胞的浸润。最后，淋巴管内皮细胞的增殖可能与癌细胞的淋巴浸润相关。
