【作者】 付占昭； 顾涛； 张绍华； 董立新；

【机构】 秦皇岛市第一医院肿瘤科； 唐山工人医院肿瘤科；

【摘要】 目的:研究c—erbB-2／HER2基因在非小细胞肺癌(non-small cell lung carcinoma,NSCLC)中的表达及其与临床病理特征的关系,探讨c—erbB-2基因在NSCLC 预后中的地位。方法:采用免疫组织化学Power VisionTM 法检测110例手术切除的NSCLC及20例肿瘤远端正常肺组织中c—erbB-2基因的表达情况,并收集全部患者的临床病理资料,进行随访调查。应用Ridit检验,线性趋势x 2检验及Spearman等级相关分析c—erbB-2基因表达与临床病理特征的关系。生存分析采用寿命表法,组间比较用Log- rank检验,多因素分析采用COX比例风险模型。根据多因素分析结果建立预后指数(PI)方程,计算出每个患者的PI 值,并进行聚类分析,确定不同的预后亚群。结果:①c— erbB-2基因在NSCLC组织中的阳性表达率为36．4％,明显高于肿瘤远端正常肺组织中的表达(10．0％)(P<0．05)。② c—erbB-2基因表达与患者性别,CT深分叶征,肿瘤组织类型及病理分级有关(P<0．05),与淋巴结转移和pTNM分期呈显著正相关(r=0．41 8和0．290,P<0．05),且具有线性趋势(P<0．05),而与年龄,吸烟史,术前Karnofsky评分,术前血小板记数,CT毛刺征,肿瘤的部位及大小无关 (P>0．05)。性别为女性,有深分叶征,组织类型腺癌,病理分级G3,淋巴结转移N2,pTNM分期Ⅲ期者,其c— erbB-2基因阳性表达率显著高于无上述条件者(P<0．05)。③应答的94例患者术后生存期中位数为32．5月,1年,3 年,5年生存率分别为93．6％,46．0％和18．6％,单因素分析显示:性别,血小板记数,CT深分叶征,毛刺征,术后化疗,术后复发和(或)转移,肿瘤大小,病理分级,淋巴结转移,pTNM分期和c-erbB-2基因表达水平均是影响患者预后的危险因素(P<0．05)。④多因素COX回归分析显示: c-erbB-2基因表达水平,pTNM分期,CT深分叶征,术后复发和(或)转移及术后化疗对预后的影响有统计学意义 (OR=3．552,2．464,1．939,1．874和0．319,P<0．05)。⑤根据PI值将全部患者划分为高危组,中危组和低危组,三组5年生存率分别为0．0％,0．0％和33．3％,三组的预后两两之间均存在统计学差异(P<0．05)。结论:①c-erbB-2基因表达在NSCLC的发生发展中起促进作用。②c—erbB-2基因表达与患者CT深分叶征,肿瘤组织类型,病理分级有关,与淋巴结转移,pTNM分期呈显著正相关,且具有线性趋势。③c- erbB-2表达水平,pTNM分期,CT深分叶征,术后复发和(或)转移,术后化疗是NSCLC患者预后的独立因素,c- erbB-2阳性表达者提示预后不良。检测NSCLC中c-erbB- 2基因表达对进一步了解NSCLC生物学行为和判断预后有较高的价值。④PI值计算简单,在临床医师对患者作出治疗方案及进行临床实验分组时可提供有价值的参考。更多还原

【Abstract】 Objective: To study the relationship between expression of c-erbB-2/HER2 gene with the clini-copathological characteristics and the prognosis in primary non-small cell lung carcinoma patients. Methods: 110 paraffin-embedded non-small cell lung carcinomas and 20 normal lung tissues far from carcinomas were stained with monoclonal antibodies c-erbB-2 using the Power VisionTM method. The data of clinicopathological parameters were collected and all patients were followed-up. The relationship between expression of c-erbB-2 gene with the clinicopathological characteristics was analyzed by Ridit test, Chi-square test for linear trend and Spearman grade-related test. Survival analysis was performed by life table method; comparison among/between groups was performed using Log-rank test; multivariate analysis was carried out using COX proportional hazard model. The prognostic index(PI) equation was established on basis of multivariate analysis. Patients were classified to different hazard groups according to the individualized PI values that had been processed by cluster analysis.Results: The positive rate of expression of c-erbB-2 gene was significantly higher in the tumor tissues(36.4%) than that in the normal lung (10.0%) (P < 0.05). The expression of c-erbB-2 gene was correlated with sex, deep tabulation, histological types and pathological grade(P < 0.05). Expression of c-erbB-2 gene was positively related to lymph node metastasis and pTNM stage (r= 0.418 and 0.290) and had linear trend with them(P < 0.05), but was not with age, smoking history, grade of Karnofsky, number of blood platelet, spiculation, tumor location and size(P > 0.05). In cases with female, deep tabulation, adenocarcinoma, pathological grade G3, lymph node metastasis N2 and pTNM stage III, positive rate of expression of c-erbB-2 gene was significantly higher than that in those without the conditions mentioned above (P < 0.05). The median of survival time for all patients was 32.5 months. The 1,3,5 years survival rates were 93.6%, 46.0% and 18.6%, respectively. Univariate analysis showed that sex, number of blood platelet, deep lobulation, spiculation, postoperative chemotherapy, postoperative recurrence or/and metastasis, tumor size, pathological grade, lymph node metastasis, pTNM stage and levels of c-erbB-2 gene were risk factors of the prognosis of the patients(P < 0.05). Multivariate analysis showed the prognosis statistically correlated with levels of c-erbB-2 gene, pTNM stage, deep lobulation, postoperative recurrence or/ and metastasis and postoperative chemotherapy(OR=3.552, 2.464,1.939,1.874 and 0.319, P < 0.05). The patients were divided into high-risk group, moderate-risk group and low-risk group according to the PI value, and the 5-year survival rates were 0.0%, 0.0% and 33.3%, respectively. There was a significant difference in the survival rates be- tween each two groups of the three groups (P < 0.05). Conclusion: c-erbB-2 gene can possibly plays a promoting更多还原