Giatromanolaki A, Koukourakis M I, O'Byrne K, Kaklamanis L, Dicoglou C, Trichia E, Whitehouse R, Harris A L, Gatter K C
Department of Cellular Science, John Radcliffe Hospital, Oxford, U.K.
Anticancer Res. 1996 Nov-Dec;16(6B):3819-25.
Tumour angiogenesis is an important prognostic factor in non-small cell lung cancer. Recently, EGFR and c-erbB-2 protein was found to regulate cell adhesion and the invasive growth of cancer through its association with the cadherin-catenin complex. The role of c-erbB-2 protein in cell migration has been also reported. In this study we investigate the combined role of tumoral neoangiogenesis and c-erbB-2/EGFR expression in the metastatic behaviour and prognosis of operable non-small cell lung cancer. 107 tumour samples from patients suffering from operable non small cell lung cancer were examined. EGFR and c-erbB-2 were not correlated with each other. C-erbB-2 expression was associated with low angiogenesis, approaching statistical significance in adenocarcinomas (p = 0.08). The absence of expression of both c-erbB-2 and EGFR oncogenes in tumours with high angiogenesis, was most frequently observed in node negative cases (p = 0.04). C-erbB-2 overexpression defined a subgroup of node negative patients with low angiogenesis and prognosis similar to patients with tumours bearing high angiogenesis. These findings support the hypothesis that expression of the erb genes is a mechanism activated in non-small cell lung cancer to enable cancer cell migration. This pathway seems to be activated mainly in tumours with poor vasculature presumably lading to an unfavourable intratumoral nutritional and oxygen ambience.
肿瘤血管生成是非小细胞肺癌的一个重要预后因素。最近,发现表皮生长因子受体(EGFR)和c-erbB-2蛋白通过与钙黏蛋白-连环蛋白复合体结合来调节细胞黏附和癌症的侵袭性生长。也有报道称c-erbB-2蛋白在细胞迁移中发挥作用。在本研究中,我们调查了肿瘤新生血管生成与c-erbB-2/EGFR表达在可手术切除的非小细胞肺癌转移行为和预后中的联合作用。对107例可手术切除的非小细胞肺癌患者的肿瘤样本进行了检查。EGFR和c-erbB-2彼此不相关。c-erbB-2表达与低血管生成相关,在腺癌中接近统计学意义(p = 0.08)。在高血管生成的肿瘤中,最常观察到c-erbB-2和EGFR癌基因均不表达的情况,在无淋巴结转移的病例中最为常见(p = 0.04)。c-erbB-2过表达定义了一个无淋巴结转移患者的亚组,其血管生成低,预后与高血管生成肿瘤患者相似。这些发现支持了以下假设,即erb基因的表达是在非小细胞肺癌中激活的一种机制,以促进癌细胞迁移。这条途径似乎主要在血管系统不良的肿瘤中被激活,可能导致肿瘤内不利的营养和氧气环境。