CK在Ⅰ期非小细胞肺癌患者淋巴结中的表达及其临床意义

Clinical Significance of Immunohistochemically Detecting Positive Expression of Cytokeratin in Lymph Nodes of Patients with Stage I Non-Small Cell Lung Cancer

目的通过检测Ⅰ期非小细胞肺癌(NSCLC)患者淋巴结中细胞角蛋白(CK)的表达,确定微转移灶的存在及其与肿瘤复发、转移和预后的关系。方法以CK作为肿瘤标记物,应用免疫组化链霉亲生物素-生物素-过氧化酶复合物(Streptavidin biotin-peroxidase complex,SABC)法,检测根治术后常规病理HE染色阴性的33例Ⅰ期NSCLC患者的246枚淋巴结中的微转移灶。结果33例患者246枚淋巴结中有10例(30.3%)患者的12枚(4.9%)淋巴结中CK阳性表达。有或无CK阳性表达的患者复发转移率差异有统计学意义(80.0%vs.26.1%,χ2=7.015,P=0.016),CK阳性表达患者的中位生存期显著短于CK阴性表达者(21个月vs.60个月,P=0.016);Cox单因素风险模型(P=0.004)和多因素风险模型(P=0.004)均显示存在淋巴结微转移的期NSCLC患者预后不良。结论CK免疫组化染色可以作为检测和判定肺癌淋巴结微转移的有效方法。CK免疫组化染色检测淋巴结微转移与Ⅰ期NSCLC复发转移相关,有助于更加精确的分期,可以作为Ⅰ期NSCLC患者根治术后的一个预后指标,并为其综合治疗提供理论依据。

Objective To detect the positive expression of Cytokeratin （CK） in lymph nodes of patients with stage I non-small cell lung cancer （NSCLC） to confirm the presence of micrometastasis and to study the correlation with recurrence, metastases and prognosis. Methods A total of 246 hilar and mediastinal lymph nodes indicated to be tumor cells free by conventional histopathologic methods were removed during surgery from 33 patients with completely resected stage I NSCLC. The lymph ndoes were analyzed for micrometastasis by Streptavidin Biotin- Peroxidase Complex（SABC） technology using CK as a micrometastatic marker. Results CK-positive cells were detected in 12 （4.9 % ） of 246 lymph nodes, in 10 （30.3 % ） of 33 patients. There was significant difference between the recurrence and metastases rate of patients with or without positive expression of CK（80. 0% vs. 26. 1% ,X^2= 7. 015,P=0. 016）. The median survival period of patients with positive expression of CK was significantly shorter than those with negative expression of CK （21months vs. 60months, P = 0. 016）. The patients with positive expression of CK in the lymph nodes had a poor prognosis by both univariate （P = 0. 004） and multivariate analyses （P = 0. 004）. Conclusions Immunohistochemical stain for CK is a valid method for detecting and assessing micrometastasis in lymph nodes of lung cancer patients. The detection of lymph nodal micrometastatic tumor cells by immunohistochemistry using CK provides an accurate assessment of tumor staging and has powerful prognostic implications for completely resected stage I NSCLC patients and provides theoretical evidence for synthetic therapy of stage I NSCLC patients.