肺腺癌患者表皮生长因子受体突变状态与组织病理亚型及CT特征的相关性研究

张连斌; 申磊磊; 王波; 马克峰; 任志鹏

doi:10.3969/j.issn.2095-5227.2021.10.006

肺腺癌患者表皮生长因子受体突变状态与组织病理亚型及CT特征的相关性研究

Correlation between epidermal growth factor receptor mutation and histologic subtypes or characteristics of computed tomography findings in patients with pulmonary adenocarcinoma

摘要

摘要:
背景肺腺癌患者表皮生长因子受体(epidermal growth factor receptor，EGFR)突变状态与病理学及影像学特征的相关性是近年来的研究热点，相关研究结果参差不齐。
目的分析以磨玻璃结节(ground-glass nodule，GGN)为特征的肺腺癌患者EGFR突变状态与组织病理亚型及CT特征的相关性。
方法回顾性纳入2018年1月-2019年12月在我中心胸外科手术切除后病理证实为肺腺癌患者，根据EGFR突变状态分为突变组和野生型组，分析两组间组织病理学亚型、CT特征及分子检测结果。
结果共纳入94例术前CT表现为GGN、术后病理为肺腺癌患者，其中突变组67例，平均年龄(58.61 ± 8.22)岁，男性21例，女性46例；野生型组27例，男性10例，女性17例，平均年龄(52.89 ± 10.45)岁。野生型组年龄小于突变组(P=0.006)。EGFR突变组浸润性腺癌的比例高于野生型组(91.0% vs 63.0%， P=0.001)，在以贴壁为主的病理亚型中比例低于野生型组(38.8% vs 63.0%， P=0.033)，突变组更易出现胸膜浸润(44.8% vs 18.5%， P=0.017)，且增殖指数Ki-67高于野生型组(P=0.001)。突变组中合并肿瘤蛋白p53(TP53)突变占比高于野生型组(14.9% vs 0，P=0.030)。突变组患者GGN直径大于野生型组(P=0.011)，且mGGN数量占比更高(85.1% vs 44.4%， P＜0.001)。边缘特征方面，野生型组中GGN形状规则占比更高(55.6% vs 28.4%，P=0.013)，但突变组的GGN分叶征(44.8% vs 7.4%，P=0.001)、毛刺征(64.2% vs 25.9%，P=0.001)、空泡征(76.1% vs 51.9%，P=0.021)、血管集束征(59.7% vs 18.5%，P＜0.001)、支气管充气征(35.8% vs 11.1%，P=0.017)比例高于野生型组。突变组GGN的结节实性成分比值(consolidation tumor ratio，CTR)大于野生型组(P=0.003)。ROC曲线分析，以CTR值0.35为临界值鉴别EGFR突变型和野生型，敏感度为71.6%，特异性为70.4%，ROC曲线下面积(AUC)为0.708。
结论 GGN、mGGN直径较大以及CTR值 ≥ 0.35的肺腺癌更易出现EGFR突变，且这部分患者更易合并TP53突变。

Abstract:
Background The correlation between epidermal growth factor receptor (EGFR) mutation status and histologic subtypes or characteristics of computed tomography findings in lung adenocarcinoma has been a research hotspot in recent years, and the results are various.
Objective To investigate the correlation between EGFR mutation and histologic subtypes or characteristics of computed tomography findings in patients with adenocarcinoma.
Methods Patients with pulmonary adenocarcinoma and ground-glass nodule (GGN) who underwent surgery from January 2018 to December 2019 were enrolled in this study. The patients were divided into mutation group (n=67, 21 males and 46 females) and wild-type group (n=27, 10 males and 17 females). Computed tomography (CT) findings, histologic subtypes, and EGFR mutation status were analyzed.
Results Totally 94 cases who were manifested as GGN preoperatively and with pathological results of lung adenocarcinoma postoperatively were included. The age of patients with EGFR mutation was significantly older than those with wild-type EGFR (58.61 ± 8.22 years vs 52.89 ± 10.45 years, P=0.006). The proportion of adenocarcinoma in the mutation group was higher than that in the wild-type group (91.0% vs 63.0%, P=0.001), while the proportion of lepidic predominant adenocarcinoma (LPA) subtype in the mutation group was significantly less than that in the wild-type group (38.8% vs 63%, P=0.033). Statistical difference was also found in visceral pleural invasion (44.8% vs 18.5%, P=0.017) and Ki-67 labeling index values (P=0.001). More concurrent TP53 mutation was found in the mutation group than that in the wild-type group (14.9% vs 0, P=0.030). By CT, a statistical significance was observed in the diameter of GGN (P=0.011) and the quantity of mixed GGN (mGGN) (85.1% vs 44.4%, P＜0.001). Less irregularity (28.4% vs 55.6%, P=0.013), lobulation (7.4% vs 44.8%, P=0.001), spiculation (25.9% vs 64.2%, P=0.001), vacuole (51.9% vs 76.1%, P=0.021), vessel convergence (18.5% vs 59.7%, P＜0.001) and air-bronchogram (11.1% vs 35.8%, P=0.017) were seen in the wild-type group than that in the mutation group. However, the CTR value of the mutation group was significantly higher than that in the wild-type group (P=0.003). According to ROC curve analysis, the EGFR mutation and the wild-type were identified by a critical value of 0.35, with a sensitivity of 71.6%, specificity of 70.4%, and the area under the ROC curve (AUC) of 0.708.
Conclusion Patients with larger GGN diameters, mGGN and CTR ≥ 0.35 are more likely to have EGFR mutations, and concurrent TP53 mutation is relatively frequent in these patients.

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