Takahashi Yutaka, Kitadai Yasuhiko, Ellis Lee M, Bucana Corazon D, Fidler Isaiah J, Mai Masayoshi
Department of Surgical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa 920-8640, Japan.
Jpn J Cancer Res. 2002 Nov;93(11):1258-65. doi: 10.1111/j.1349-7006.2002.tb01232.x.
We examined the expression level of several genes that regulate different steps in metastasis formation in formalin-fixed, paraffin-embedded biopsies of 189 primary human gastric carcinomas prior to surgical resection in patients in whom lymph node metastasis was not evident by endoscopic ultrasound or computed tomography (CT) scan. The expressions of epidermal growth factor receptor (EGF-R), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2 and E-cadherin were examined by a colorimetric in situ mRNA hybridization technique. The integrity of the mRNAs was verified, leaving 161 (85.2%) patients for study. After gastrectomy, 82 patients had positive lymph nodes and 79 patients had negative lymph nodes. The concurrent expression levels of MMP-2 and E-cadherin mRNAs were significantly higher and lower, respectively, in the metastatic tumors than the non-metastatic tumors. Expression of EGF-R and VEGF was not different between the metastatic and non-metastatic tumors. However, when only the intestinal-type of gastric cancer was evaluated, the level of VEGF mRNA was significantly higher in tumors associated with lymph node metastasis than in those without metastasis. However, a high MMP-2:E-cadherin ratio significantly correlated with lymph node metastasis in both types of gastric cancer. These results suggest that multiparametric in situ hybridization analysis for several metastasis-related genes may allow the preoperative prediction of lymph node metastasis from gastric cancer.
我们在189例原发性人类胃癌患者手术切除前，对其经福尔马林固定、石蜡包埋的活检组织中调控转移形成不同步骤的几个基因的表达水平进行了检测。这些患者经内镜超声或计算机断层扫描（CT）检查未发现明显的淋巴结转移。采用比色原位mRNA杂交技术检测表皮生长因子受体（EGF-R）、血管内皮生长因子（VEGF）、基质金属蛋白酶（MMP）-2和E-钙黏蛋白的表达。对mRNA的完整性进行了验证，最终有161例（85.2%）患者纳入研究。胃切除术后，82例患者出现淋巴结阳性，79例患者淋巴结阴性。转移瘤中MMP-2和E-钙黏蛋白mRNA的同时表达水平分别显著高于和低于非转移瘤。转移瘤和非转移瘤中EGF-R和VEGF的表达无差异。然而，仅评估肠型胃癌时，伴有淋巴结转移的肿瘤中VEGF mRNA水平显著高于无转移的肿瘤。然而，高MMP-2:E-钙黏蛋白比值在两种类型的胃癌中均与淋巴结转移显著相关。这些结果表明，对几个转移相关基因进行多参数原位杂交分析可能有助于术前预测胃癌的淋巴结转移。
