Ardizzoni A, Cafferata M A, Paganuzzi M, Filiberti R, Marroni P, Neri M, Fontana V, Nicoló G, Perdelli L, Stampino C G, Rosso R, Puntoni R
Divisione di Oncologia Medica I, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132 Genoa, Italy.
Cancer. 2001 Oct 1;92(7):1896-904.
HER-2/neu tissue overexpression is found in nearly 15% of patients with nonsmall cell lung carcinoma and is reported to affect prognosis adversely in surgical series. However, the prognostic role of serum HER-2/neu oncoprotein, particularly in patients with advanced lung carcinoma, remains unknown. This study was designed to assess the potential value of measuring serum levels of HER-2/neu oncoprotein in predicting response to treatment and survival in patients with locally advanced and metastatic nonsmall cell lung carcinoma.
Baseline serum HER-2/neu levels (fm/mL) were studied using an enzyme-linked immunosorbent assay method in 84 patients with newly diagnosed, advanced nonsmall cell lung carcinoma who underwent chemotherapy.
The patients enrolled in the study included 76 males and 8 females, with a median age of 62 years (range, 36-73 years) and a median performance status of 1. Fifty patients (59.5%) had nonsquamous histology, and 34 patients (40.5%) had squamous cell carcinoma. Thirty-four patients (40.5%) had Stage III disease, and 50 patients (59.5%) had Stage IV disease. The mean baseline value of HER-2/neu in the whole series was 56.1 fm/mL (range, 13.0-103.8 fm/mL). HER2 immunohistochemistry on paraffin embedded tissue was performed in 18 patients. HER-2/neu tissue overexpression was found in only one patient, who also showed high serum levels (102 fm/mL). No correlation was observed between protein serum quantitation and gender, age, histology, stage, performance status, leukocyte count, or smoking. Nonresponding and responding patients exhibited similar oncoprotein levels (median, 57.6 fm/mL vs. 51.9 fm/mL, respectively). The overall survival rate was 42.5% at 1 year and 12% at 2 years, with a median survival duration of 10 months. At univariate analysis, high HER-2/neu serum levels were associated with an unfavorable survival outcome. Using a cut-off point for HER-2/neu of 73.0 fm/mL (corresponding to the 80th percentile of protein concentration), the survival of patients who had higher serum levels of HER-2/neu was significantly worse compared with patients who had lower serum levels (median, 7.1 months vs. 10.9 months; P = 0.004). Multivariate analysis confirmed the independent predictive value of serum HER-2/neu concentration as a negative prognostic factor (P = 0.02).
High pretreatment levels of HER-2/neu oncoprotein are associated with an adverse prognostic impact on survival in patients with locally advanced or metastatic nonsmall cell lung carcinoma.
在近15%的非小细胞肺癌患者中发现HER-2/neu组织过表达，据报道这在外科手术系列研究中对预后有不利影响。然而，血清HER-2/neu癌蛋白的预后作用，尤其是在晚期肺癌患者中，仍不清楚。本研究旨在评估检测血清HER-2/neu癌蛋白水平在预测局部晚期和转移性非小细胞肺癌患者治疗反应和生存方面的潜在价值。
采用酶联免疫吸附测定法研究了84例新诊断的晚期非小细胞肺癌且接受化疗患者的基线血清HER-2/neu水平（飞摩尔/毫升）。
纳入研究的患者包括76名男性和8名女性，中位年龄62岁（范围36 - 73岁），中位体能状态为1。50例患者（59.5%）为非鳞状组织学类型，34例患者（40.5%）为鳞状细胞癌。34例患者（40.5%）为Ⅲ期疾病，50例患者（59.5%）为Ⅳ期疾病。整个系列中HER-2/neu的平均基线值为56.1飞摩尔/毫升（范围13.0 - 103.8飞摩尔/毫升）。对18例患者进行了石蜡包埋组织的HER2免疫组化检测。仅在1例患者中发现HER-2/neu组织过表达，该患者血清水平也较高（102飞摩尔/毫升）。未观察到蛋白血清定量与性别、年龄、组织学类型、分期、体能状态、白细胞计数或吸烟之间存在相关性。无反应和有反应的患者表现出相似的癌蛋白水平（中位数分别为57.6飞摩尔/毫升和51.9飞摩尔/毫升）。1年总生存率为42.5%，2年为12%，中位生存时间为10个月。单因素分析显示，HER-2/neu血清高水平与不良生存结果相关。采用HER-2/neu的截断值73.0飞摩尔/毫升（对应于蛋白浓度的第80百分位数），血清HER-2/neu水平较高的患者与较低水平的患者相比，生存情况明显更差（中位数分别为7.1个月和10.9个月；P = 0.004）。多因素分析证实血清HER-2/neu浓度作为阴性预后因素具有独立预测价值（P = 0.02）。
HER-2/neu癌蛋白的预处理高水平与局部晚期或转移性非小细胞肺癌患者的生存不良预后影响相关。
