食管小细胞癌肿瘤标志物与淋巴结转移和预后的相关性分析

Tumor markers related to lymph node metastasis and prognosis for small cell esophageal cancer in limited stage

目的随着食管小细胞癌肿瘤标志物检测在临床诊断中的广泛应用,其与食管小细胞癌临床病理因素的关系也逐渐引起人们的关注。本研究通过探讨原发性局限期食管小细胞癌肿瘤分子标志物和患者淋巴结转移及预后的关系,以期为临床提供参考。方法回顾性分析2004-01-01-2012-12-31河北医科大学第四医院收治并行肿瘤分子标志物检测的局限期食管小细胞癌患者82例,其中接受CD56检测82例,突触素（synaptophysin,Syn）检测82例,嗜铬粒-A（chromogranin A,CHr-A）检测81例,角蛋白（cytokeratin,CK）检测78例,神经元特异性烯醇化酶（neuron-specific enolase,NSE）检测70例。比较肿瘤分子标志物不同水平间患者淋巴结转移及预后情况。结果食管小细胞癌术前镜检确诊率为40.6%（28/69）。肿瘤分子标志物检测CD56的阳性率为92.7%（76/82）,Syn为90.2%（74/82）,Chr-A为27.2%（22/81）,CK为89.7%（70/78）,NSE为60.0%（42/70）。Chr-A阴性及弱阳性组患者淋巴结转移度为11.6%（53/457）,显著高于阳性组的4.3%（6/138）,χ2=6.236,P=0.013;NSE阳性组淋巴结转移度为11.8%（40/338）,较阴性及弱阳性组的7.0%（14/201）有增高趋势,χ2=3.315,P=0.069。CD56、Syn、Chr-A和CK阳性组患者与阴性及弱阳性组患者局控率、远转率及生存率差异均无统计学意义,P〉0.05。NSE阴性及弱阳性组5年局控率和生存率分别为77.2%和44.2%,优于NSE阳性组的61.9%和23.1%,χ2值分别为4.677和4.000,P值分别为0.031和0.045;NSE阳性组5年远转率为62.7%,显著高于NSE阴性及弱阳性患者的37.0%,χ2=4.146,P=0.042。多因素分析显示,化疗与否（P〈0.001）和NSE表达水平（P=0.035）是局限期食管小细胞癌生存的独立影响因素。结论食管小细胞癌术前镜检确诊率较低,对神经源性特异性抗体表达有明显的亲和性。Chr-A阴性、弱阳性患者淋巴结转移度较Chr-A阳性患者明显升高。化疗与否和NSE表达水平是局限期食管小细胞癌生存的独立影响因素。

OBJECTIVE With the wide application of tumor marker detection in the clinical diagnosis of small cell carcinoma of esophagus,the relationship between the clinical pathological factors and the clinical pathological factors of small cell carcinoma of the esophagus has gradually attracted people＇s attention.This study was to explore the primary limited stage small cell carcinoma of the esophagus tumor molecular markers and lymph node metastasis and prognosis,so as to provide reference for the clinical.METHODS Eighty-two cases of small cell carcinoma of esophagus were retrospectively analyzed in the Fourth Hospital of Hebei Medical University from January 1st,2004 to December 31 st,2012.The patients with small cell carcinoma of esophagus were treated with concurrent tumor markers.Of the patients,82 cases received CD56 detection,82cases received synaptophysin（Syn）detection,81 cases received CHr-A detection,78 cases received CK detection,70 cases received neuron-specific enolase（NSE）detection.Tumor markers of different levels in patients with lymph node metastasis and prognosis were compared.RESULTS The preoperative diagnosis rate of small cell carcinoma of the esophagus by microscopic examination was 40.6%（28/69）.The positive rate of CD56 was 92.7%（76/82）,Syn was 90.2%（74/82）,Chr-A was 27.2%（22/81）,CK was 89.7%（70/78）,NSE was 60.0%（42/70）by tumor marker detection.The lymph node metastasis ratios with Chr-A negative and weak positive group were much higher than that with Chr-A positive group[11.6%（53/457）vs 4.3%（6/138）,χ2=6.236,P=0.013].There was a tendency that lymph node metastasis ratio of NSE positive group was much higher than that of NSE negative group and weak positive group[11.8%（40/338）vs 7.0%（14/201）,χ2=3.315,P=0.069].Compared with local control rates,in distant metastasis rates and survival rates,there were no significant differences between different levels of tumor markers of CD56,Syn,Chr-A and CK（P〉0.05）.Survival rate and local control rate of NSE negative,weak positive group were higher than that of NSE positive group（44.2%vs 23.1%,χ2=4.000,P=0.045;77.2% vs 61.9%,χ2=4.677,P=0.031）,and the NSE positive group had higher tendency to be metastasis（62.7% vs 37.0%,χ2=4.146,P=0.042）.Multivariate analysis showed that chemotherapy or not（P0.001）and NSE expression levels（P=0.035）were independent predictors of limited stage small cell carcinoma of the esophagus survival.CONCLUSIONS Small cell carcinoma of the esophagus microscopic examination of the preoperative diagnosis rate is low.Small cell carcinoma of the esophageal highly express neuroendocrine antigene.The lymph node metastasis ratios with Chr-A negative and weak positive group were much higher than that with Chr-A positive group.Chemotherapy or not and NSE expression level is independent factors of limited stage small-cell esophageal cancer survival.