气腔扩散阳性的肺腺癌临床病理学特征分析

Analysis of Clinicopathological Features on Spread Through Air Spaces of Lung Adenocarcinoma

背景与目的气腔扩散(spread through air spaces,STAS)作为一种新发现的肺癌侵袭方式,其生物学特点及分子特征尚存在争议。本研究旨在探讨STAS与肺浸润性腺癌临床病理学特征及基因改变的关系。方法选取广州医科大学附属第一医院2019年7月至2021年3月确诊的肺非黏液性浸润性腺癌手术切除标本694例,分析STAS与临床病理因素之间的关系。应用免疫组织化学方法检测间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)蛋白表达;应用扩增阻滞突变系统-聚合酶链反应(amplification refractory mutation system-polymerase chain reaction,ARMS-PCR)技术检测表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变;应用反转录-PCR(reverse transcription-PCR,RT-PCR)技术检测肉瘤致癌因子受体(ROS proto-oncogene 1-receptor,ROS1)基因融合。结果STAS阳性病例共344例,STAS阴性病例共350例。STAS阳性与肿瘤最大径(P<0.001)、胸膜侵犯(P<0.001)、脉管侵犯(P<0.001)、神经束侵犯(P=0.013)、淋巴结转移(P<0.001)、临床分期(P<0.001)及组织学分型(P<0.001)相关;STAS与ALK蛋白表达(P<0.001)相关。多因素分析表明,STAS阳性与胸膜侵犯(P=0.001)、脉管侵犯(P<0.001)、淋巴结转移(P=0.005)及ALK蛋白表达(P=0.032)相关。结论STAS阳性与肺腺癌高侵袭性生物学行为有关,提示不良预后。

Background and objective The biological and molecular characteristics of spread through air spaces(STAS),a newly recognized invasive mode of lung cancer,remain controversial.The aim of this study was to investigate the clinicopathological features and molecular characteristics of STAS in patients with pulmonary adenocar-cinoma.Methods A total of 694 resected invasive non-mucinous lung adenocarcinomas diagnosed by clinicopathology from July 2019 to March 2021 in the First Affiliated Hospital of Guangzhou Medical University were collected,and the relationship between STAS and clinicopathological factors was analyzed.The state of protein expression of anaplastic lymphoma kinase(ALK)was detected by immunohistochemical method.Epidermal growth factor receptor(EGFR)was detected by amplification refractory mutation system-polymerase chain reaction(ARMS-PCR).ROS proto-onco-gene 1-receptor(ROS1)was detected by reverse transcription-PCR(RT-PCR).Results A total of 344 STAS positive cases and 350 STAS negative cases were collected.By univariate analysis,STAS positivity was statistically associated with tumor maximum diameter(P<0.001),pleural invasion(P<0.001),lymphovascular invasion(P<0.001),nerve in-vasion(P=0.013),lymph node metastasis(P<0.001),clinical stage(P<0.001)and histological type(P<0.001).There was a statistical correlation between STAS and ALK protein expression(P=0.001).Multivariate analysis showed that STAS positive was correlated with pleural invasion(P=0.001),vascular invasion(P<0.001),lymph node metastasis(P=0.005)and ALK protein expression(P=0.032).Conclusion STAS is associated with highly aggressive biological behavior of lung adenocarcinoma,suggesting a poor prognosis.