Sato F, Shimada Y, Watanabe G, Uchida S, Makino T, Imamura M
Department of Surgery and Surgical Basic Science, Graduate School of Medicine, Kyoto University, Japan.
Br J Cancer. 1999 Jul;80(9):1366-72. doi: 10.1038/sj.bjc.6690530.
Lymph node metastasis is a strong independent prognostic factor for oesophageal cancer. The expression of matrix metalloproteinases (MMPs) and reduction of E-cadherin correlate with lymph node metastasis of oesophageal cancer. We previously reported that the expression of vascular endothelial growth factor (VEGF) is associated with lymph node metastasis. This study was designed to determine whether VEGF, MMP-9 and E-cadherin expression is stable or changes in the process of lymph node metastasis of oesophageal cancer. Using immunohistochemistry, we detected VEGF, MMP-9 and E-cadherin expression in paraffin-embedded specimens of oesophageal squamous cell carcinoma. We classified 134 primary tumours and 174 nodal metastases using two different criteria: the absence [Group N(-)] or presence [Group N(+)] of nodal metastasis, and the stage of metastasis--Early Stage (cancer cells < 50% of lymph node) or Late Stage (> or = 50%)--and compared the expression among two groups and among two stages. The expression rates of Group N(-), Group N(+), Early Stage and Late Stage are as follows: VEGF (49%, 74%, 60%, 33%), MMP-9 (76%, 65%, 95%, 69%) and E-cadherin (49%, 24%, 55%, 38%). VEGF expression was down-regulated in Late Stage lymph node metastasis, while MMP-9 expression was elevated in Early Stage metastasis. E-cadherin expression is restored somewhat in Early Stage metastasis, but suppressed again in Late Stage metastasis. These data suggest that the expression of VEGF, MMP-9 and E-cadherin each change in the process of lymph node metastasis in oesophageal cancer, and that the patterns of change are different.
淋巴结转移是食管癌一个强有力的独立预后因素。基质金属蛋白酶（MMPs）的表达以及E-钙黏蛋白的减少与食管癌的淋巴结转移相关。我们之前报道过血管内皮生长因子（VEGF）的表达与淋巴结转移有关。本研究旨在确定VEGF、MMP-9和E-钙黏蛋白的表达在食管癌淋巴结转移过程中是稳定的还是会发生变化。我们采用免疫组织化学方法检测了食管鳞状细胞癌石蜡包埋标本中VEGF、MMP-9和E-钙黏蛋白的表达。我们使用两种不同标准对134例原发性肿瘤和174例淋巴结转移灶进行分类：有无淋巴结转移[无转移组N(-)，有转移组N(+)]，以及转移阶段——早期（癌细胞占淋巴结的比例<50%）或晚期（≥50%）——并比较两组之间以及两个阶段之间的表达情况。N(-)组、N(+)组、早期和晚期的表达率如下：VEGF（49%、74%、60%、33%），MMP-9（76%、65%、95%、69%）和E-钙黏蛋白（49%、24%、55%、38%）。VEGF表达在晚期淋巴结转移中下调，而MMP-9表达在早期转移中升高。E-钙黏蛋白表达在早期转移中有所恢复，但在晚期转移中再次受到抑制。这些数据表明，VEGF、MMP-9和E-钙黏蛋白的表达在食管癌淋巴结转移过程中均发生变化，且变化模式不同。
