表皮生长因子受体与非小细胞肺癌患者预后及术后生存率的关系

Epidermal growth factor receptor associated with the prognosis of patients with non-small cell lung cancer and the postoperative survival rate

目的:分析人体表皮生长因子受体1,2,3单独及联合过度表达与非小细胞肺癌患者术后的5年生存率的关系。方法:选用苏州大学附属医院1996-07/1998-12胸外科非小细胞肺癌手术蜡块标本共58例。男39例,女19例;年龄34～78岁。所有患者术前均未接受抗癌治疗。肺鳞癌32例,肺腺癌26例;Ⅰ期肺癌11例,Ⅱ期26例,Ⅲa期14例,Ⅲb期3例,Ⅳ期4例(Ⅲb,Ⅳ期为姑息手术的晚期肺癌);低分化肺癌12例,中分化肺癌31例,高分化肺癌15例;淋巴结转移41例。1999-01/2004-01采用复诊、电话、通信、登门询问的形式对患者的预后进行5年随访。采用链霉菌抗生物素蛋白-过氧化物酶连结法检测有5年随访资料的58例肺癌组织中人体表皮生长因子受体1,2,3的表达。结果:①鳞癌人体表皮生长因子受体1过度表达阳性率犤68%(25/37)犦明显高于腺癌犤32%(12/37)犦(χ2=6.348,P<0.05);有淋巴结转移患者人体表皮生长因子受体1,2,3及三者联合过度表达阳性率犤81%(30/37),82%(27/33),94%(16/17),100%(11/11)犦明显高于无淋巴结转移者犤19%(7/37),18%(6/33),6%(1/17),0犦(χ2=4.576～6.371,P<0.05);TNM分期Ⅰ+Ⅱ+Ⅲa期人表皮生长因子1,2,3过度表达阳性率犤81%(30/37),79%(26/33),65%(11/17)犦明显高于TNM分期Ⅲb+Ⅳ期者犤19%(7/37),21%(7/33),35%(6/17),χ2=4.518,6.031,12.224,P<0.05～0.01犦;而人体表皮生长因子受体1,2,3联合过度表达阳性率明显低于TNM分期Ⅲb+Ⅳ期者犤45%(5/11),55%(6/11),χ2=23.079,P<0.01犦。②人体表皮生长因子受体2,人体表皮生长因子受体3过度表达与病理类型鳞癌和腺癌无相关性(P>0.05);人体表皮生长因子受体1过度表达与肺癌病理类型相关(｜r｜=0.331,P<0.05)。人体表皮生长因子受体2,1,3过度表达与淋巴结转移及TNM分期相关(｜r｜=0.279～0.459,P<0.05～0.01),与肺癌的分化程度不相关。人体表皮生长因子受体2过度表达组的5年生存率明显低于非过度表达组(P<0.05)。人体表皮生长因子受体2,1,3联合过度表达组的5年生存率明显低于非联合过度表达组(P<0.01)。结论:有淋巴结转移、鳞癌、TNM分期Ⅰ+Ⅱ+Ⅲa期患者更易检测到人体表皮生长因子受体2,1,3的过度表达阳性;人体表皮生长因子受体2,1,3联合过度表达肺癌患者5年生存率低于人体表皮生长因子受体2,1,3的过度表达患者,人体表皮生长因子受体2的过度表达患者5年生存率低于非过度表达患者。

AIM:To analyze the relationship between the over-expression of separate and combined human epidermal growth factor receptor(HER)-1,2,3 and the 5-year survival rate in patients with non-small cell lung cancer(NSCLC) after operation. METHODS:Between July 1996 and December 1998,58 cases of paraffin embedded tissues of NSCLC were obtained from the archival collections at the Department of Thoracic Surgery in the Affiliated Hospital of Soochow University.All patients consisted of 39 males and 19 females,aged from 34 to 78 years.None of patients received preoperative anticancer treatment.Histopathologic subtypes were 32 squamous cell carcinomas and 26 adenocarcinomas.Pathologic stage distribution was stage Ⅰin 11 cases,stage Ⅱin 26,stage Ⅲa in 14,stage Ⅲb in 3 and stage Ⅳin 4(stage Ⅲb and Ⅳwere advanced stage lung cancer of palliative operation).All patients were assigned as poorly differentiated cancer in 12 cases,moderately differentiated cancer in 31 and well differentiated cancer in 15,and also included lymph node metastasis in 41 cases.All patients were followed by phone,letter,return visit and to call at from January 1999 to January 2004.The over-expression of HER-1,2,3 of 58 cases with 5 years of follow-up information were detected by streptavidin peroxidase(SP) complex immunohistochemical technique. RESULTS:①The positive over-expression rate of HER-1 in squamous cell carcinomas[68%(25/37)] was significantly higher than in adenocarcinomas[32%(12/37)](χ2=6.348,P< 0.05);The over-expression rates of separate and combined HER-1,2,3 with positive lymph node[81%(30/37),82%(27/33),94%(16/17),100%(11/11)] were higher than those of negative lymph node[19%(7/37)],18%(6/33),6%(1/17),0](χ2=4.576 to 6.371,P< 0.05).The positive over-expression rates of separate HER-1,2,3 at Ⅰ+Ⅱ+Ⅲa stage in TNM staging[81%(30/37),79%(26/33),65%(11/17)] were significantly higher than those at Ⅲb+Ⅳstage[19%(7/37),21%(7/33),35%(6/17)](χ2=4.518,6.031,12.224,P< 0.05 to 0.01),however,the positive over-expression rate of HER1+2+3 at Ⅰ+Ⅱ+Ⅲa stage was significantly lower than that at Ⅲb+Ⅳstage[45%(5/11) vs 55%(6/11),χ2=23.079,P< 0.01].②There was no association between the over-expression of HER-2,3 with histopathologic subtypes of squamous cell carcinomas and adenocarcinomas(P >0.05),but the over-expression of HER-1 was correlated with pathological types of lung cancer(|r|=0.331,P< 0.05).The over-expression of HER-1,2,3 was correlated with lymph node metastasis and TNM staging(|r|=0.279 to 0.459,P< 0.05 to 0.01),but not with cell differentiation.The five-year survival rate in HER-2 with over-expression was significantly lower than that in HER-2 without overexpression(P< 0.05),and that in HER2+1 +3 with overexpression was significantly lower than that in HER2+1+3 without overexpression(P< 0.01). CONCLUSION:The positive over-expression of HER1,2,3 was detected easily in patients with lymph node metastasis,squamous carcinoma,histopathologic stage Ⅰ+Ⅱ+Ⅲa in TNM staging.The five-year survival rate was higher in patients with overexpression of HER2+1+3 than that in patients with overexpression of HER1,2,3, and that in HER-2 with overexpression was lower than that in HER-2 without overexpression.