Fontanini G, De Laurentiis M, Vignati S, Chinè S, Lucchi M, Silvestri V, Mussi A, De Placido S, Tortora G, Bianco A R, Gullick W, Angeletti C A, Bevilacqua G, Ciardiello F
Dipartimento di Oncologia, Università di Pisa, Italy.
Clin Cancer Res. 1998 Jan;4(1):241-9.
We have determined the expression of transforming growth factor alpha (TGF alpha), amphiregulin (AR), CRIPTO, the epidermal growth factor receptor (EGFR), erbB-2, erbB-3, and tumor angiogenesis in a series of 195 patients with stage I-IIIA non-small cell lung cancer (NSCLC) treated with radical surgery to define their usefulness as prognostic indicators of survival. A variable degree of specific staining in cancer cells was observed for the three growth factors and for the three growth factor receptors in the majority of NSCLC patients. A statistically significant association between overexpression of TGF alpha, AR, and CRIPTO was observed. Enhanced expression of AR was significantly correlated with enhanced expression of erbB-2 and advanced T-stage. A direct association was also detected for overexpression of TGF alpha and of erbB-2 or erbB-3, respectively. Sex, tumor size, nodal status, stage, microvessel count, as a measure of neovascularization, and AR overexpression significantly correlated with overall survival at univariate analysis. In a Cox multivariate analysis, the only characteristics with an independent prognostic effect on OAS were microvessel count [relative hazard (RH), 6.61; P < 0.00001), nodal status (RH, 1.59; P = 0.0013), and AR overexpression (RH, 1.72; P = 0.02). These results suggest that evaluation of neoangiogenesis and of certain growth factors, such as AR, can be useful in addition to conventional pathological staging to select high-risk NSCLC patients who may benefit from post-surgical systemic therapies.
我们检测了195例接受根治性手术的I-IIIA期非小细胞肺癌（NSCLC）患者中转化生长因子α（TGFα）、双调蛋白（AR）、CRIPTO、表皮生长因子受体（EGFR）、erbB-2、erbB-3的表达以及肿瘤血管生成情况，以确定它们作为生存预后指标的实用性。在大多数NSCLC患者中，观察到癌细胞对这三种生长因子和三种生长因子受体有不同程度的特异性染色。观察到TGFα、AR和CRIPTO的过表达之间存在统计学上的显著关联。AR表达增强与erbB-2表达增强和T分期进展显著相关。还分别检测到TGFα与erbB-2或erbB-3过表达之间存在直接关联。在单因素分析中，性别、肿瘤大小、淋巴结状态、分期、作为新生血管形成指标的微血管计数以及AR过表达与总生存期显著相关。在Cox多因素分析中，对总生存期有独立预后影响的唯一特征是微血管计数[相对危险度（RH），6.61；P<0.00001]、淋巴结状态（RH，1.59；P = 0.0013）和AR过表达（RH，1.72；P = 0.02）。这些结果表明，除了传统的病理分期外，评估新生血管生成和某些生长因子，如AR，对于选择可能从术后全身治疗中获益的高危NSCLC患者可能是有用的。
