肺鳞状细胞癌伴神经内分泌分化与生物学特性及预后关系探讨

The Relationship between the Biological Characteristics of Squamous Cell Lung Cancer of Neuroendocrine-like Differentiation and Its Prognosis

目的:初步探讨肺鳞状细胞癌的神经内分泌分化(neuroendoerine-like differentiation,ND)情况与生物学行为和预后的关系。方法:收集手术后经病理证实为肺原发鳞癌患者120例瘤组织石蜡标本,术前均未接受放化疗。采用免疫组化二步法检测神经元特异性烯醇化酶(NSE),突触素(SYN)和嗜铬素A(CGA)的表达,采用x2检验分析ND与肺鳞癌生物学行为之间的关系,分别采用kaplan-meier生存曲线和COX风险比例模型进行单因素和多因素生存分析。结果:120例肺鳞癌中,CGA阳性率46.7%,NSE阳性率60.8%,SYN阳性率36.7%。鳞癌伴ND阳性率为40.8%。相关性分析结果示3种标志物之间无明显相关性。肺鳞状细胞癌伴ND与肿瘤细胞分化程度及瘤体分期(T分期)有关,肿瘤细胞分化越差,瘤体分期越高,ND阳性率越高。SYN的阳性表达与患者的年龄、性别及肿瘤细胞的分化程度有关,年龄越高,女性,肿瘤细胞分化越差,SYN阳性表达率越高。单因素生存分析结果经Log-Rank检验示SYN(x^2=3.961,P=0.047)及术后化疗(x^2=4.447,P=0.035)与患者的术后生存率有关,而ND与患者术后生存率无明显相关性(x^2=0.524,P=0.469)。Cox多因素生存分析结果示患者的年龄(OR=0.459,P=0.029),SYN阳性表达(OR=2.114,P=0.036),CGA阳性表达(OR=0.558,P=0.066)和术后化疗(OR=1.866,P=0.091)与患者预后相关,可作为可切除肺鳞癌患者的独立预后因素。结论:肺鳞癌伴神经内分泌分化与肿瘤细胞分化程度及瘤体分期有关,SYN和术后化疗是评价可手术患者预后的两个重要指标。

Objective： To investigate the relationship between the biological characteristics of squamous cell lung cancer of neuroendocrine-like differentiation （ND） and its prognosis. Methods： We used immunohistochemistry to detect the expression of neuron-specific enolase （NSE）, synaptophysin （SYN） and chromogranin A （CGA） in paraffin-embedded specimens of 120 cases of surgically and pathologically confirmed squamous cell lung carcinoma. The Kaplan-meier survival curve model and the COX proportional hazards model were employed for univariate and multivariate survival analysis. Results： The positive rates of CGA, NSE, and SYN expression were 46.7%, 60.8%, and 36.7%, respectively. According to the criterion that the positive expression of at least two of the above markers indicates squamous cell lung cancer with ND, the incidence rate was 40.8%. No significant correlation was found among the three markers. Squamous cell lung cancer with ND was correlated with tumor cell differentiation and T stage. The expression of SYN was correlated with age, gender and tumor cell differentiation. Survival analysis by Log-Rank test showed that SYN expression （X^2=3.961, P=0.047） and postoperative chemotherapy （X^2=4.447, P=0.035） were related to the postoperative survival rate. There was no correlation between squamous cell lung cancer with ND and survival （X^2=0-524, P=-0.469）. Cox survival analysis indicated that patient age （OR=0.459, P=0.029）, postoperative chemotherapy （OR=1.866, P=0.091） and the positive expression of SYN （OR=2.114, P=0.036） and CGA （OR=0.558, P=0.066） were correlated with survival rate. Conclusion： Squamous ceil lung cancer with ND is related to the degree of tumor differentiation and stage. Expression of SYN and postoperative chemotherapy are two parameters affecting prognosis in patients with squamous cell lung cancer with ND.