早期非小细胞肺癌前哨淋巴结微转移检测的应用研究

Applied research of micrometastasis detection in sentinel lymph node of early stage non-small cell lung cancer

目的目前,尚无检测技术可准确判断肺癌前哨淋巴结（sentinel lymph node,SLN）微转移。本研究探讨CK19和MAGE-A3表达与非小细胞肺癌（non-small cell lung cancer,NSCLC）SLN微转移的相关性及临床价值。方法选择山东大学附属山东省肿瘤医院胸外科32例接受手术治疗的临床Ⅰ~ⅡA期NSCLC患者,术中联合应用染色法（异舒泛蓝溶液）和放射同位素法（99 Tc硫胶体检测）找寻SLN,并采用免疫组化技术检测SLN及非前哨淋巴结（non-sentinel lymph node,non-SLN）中CK19和MAGE-A3抗体的表达。结果 32例患者均检测出SLN,共清除淋巴结598枚,其中SLN 103枚,non-SLN 495枚。平均每例患者清除淋巴结（18.69±8.13）枚,清除SLN（3.22±1.74）枚。免疫组化法检测到20例患者44枚SLN中CK19表达阳性,19例患者31枚SLN中MAGE-A3抗体表达阳性。SLN免疫组化检查阳性率为42.72%,明显高于常规HE染色的阳性率（25.24%）,P=0.01。SLN的阳性表达率与临床病理分期有关,P〈0.05;而与性别、年龄、肿瘤部位、分化程度、肿瘤大小和肿瘤类型无关,P〉0.05。结论 CK19和MAGE-A3是判断淋巴结微转移较好的分子标志物,通过免疫组化技术检测SLN中CK19和MAGE-A3表达有助于评估区域淋巴结微转移状况。

OBJECTIVE Because there is no detection technology can accurately detect lung cancer sentinel lymph node（SLN）micrometastasis.This study investigate the correlation and clinical value of the expression of CK19 and MAGE-A3 with the SLN micrometastasis in non-small cell lung cancer（NSCLC）.METHODS A total of 32 patients with clinical stageⅠtoⅡA NSCLC in Shandong Cancer Hospital Affiliated to Shandong University were randomized selected in this prospective study.The combined application of staining（isosulfan blue solution）and radioactive isotope method（99technetium sulfur colloid detection）were used to detecte the SLN in operation.The expressions of CK19 and MAGE-A3 in SLN and non-sentinel lymph node（non-SLN）were detected by immunohistochemistry.RESULTS Totally32 patients were detected the SLN.A total of 598 lymph nodes were examined,including 103 SLNs and 495non-SLNs,with an average of（18.69±8.1）lymph nodes and（3.22±1.74）SLNs per patient.Immunohistochemical method detected the positive expression of CK19 in 44SLNs of 20 patients,and the positive expression of MAGE-A3 in 31SLNs of19 patients.The positive rate of immunohistochemistry was 42.72%,which was significantly higher than that of routine HE staining（25.24%）,P=0.01.The expression of CK19 and MAGE-A3 in SLNs was significantly related to clinical stage（P0.05）.The expression of CK19 and MAGE-A3 in SLNs was not significantly associated with other characteristics such as the sex,age,clinical histopathology type,tumor location,differentiation degree and tumor size（P0.05）.CONCLUSIONS CK19 and MAGE-A3 are better molecular markers to determine whether the presence of lymph node micrometastases.Immunohistochemical detection of SLNs CK19 MAGE-A3 expression can significantly improve the detection rate of micrometastases.