胸水细胞蜡块在肺腺癌诊断及EGFR/ALK/ROS1基因突变检测中的应用

目的：探索肺腺癌胸水细胞蜡块在肺腺癌病理诊断及EGFR /ALK /ROS1 基因突变检测中的应用价值。方法：选取2017年1月至2021年12月在温州医科大学附属第一医院诊断为肺腺癌的41例患者胸水细胞，采用常规细胞涂片与细胞蜡块切片进行病理HE染色鉴定，并采用NGS及ARMS方法进行EGFR /ALK /ROS1 基因突变检测。结果：恶性胸腔积液（MPE）细胞涂片癌细胞鉴定敏感性为90.2%，假阴性率为9.8%，MPE细胞蜡块癌细胞鉴定敏感性为100%，假阴性率为0；MPE细胞涂片样本EGFR /ALK /ROS1 总体突变率为70.7%（29/41），其中EGFR 突变率为61.0%（25/41），ALK 融合基因检出率为7.3%（3/41），ROS1 融合基因检出率为14.6%（6/41）；MPE细胞蜡块样本中EGFR /ALK /ROS1 总体突变率为73.2%（30/41），其中EGFR 突变率为68.3%（28/41），ALK 融合基因检出率为2.4%（1/41），ROS1 融合基因检出率为4.9%（2/41）；此外，胸水细胞涂片及细胞蜡块的基因突变阳性的肺腺癌患者较未突变肺腺癌患者具有显著增加的总生存率、无进展生存率及疾病控制率。结论：与胸水细胞涂片相比，胸水细胞蜡块肿瘤检出率及EGFR /ALK /ROS1 总体突变率相对更高，可用于指导病理诊断及分子检测的靶向治疗。

Application of pleural effusion wax block in the diagnosis of lung adenocarcinoma and detection of EGFR/ALK/ROS1 gene mutation

Objective: To explore the application value of pleural effusion cell block in the pathological diagnosis of lung adenocarcinoma and the detection of EGFR/ALK/ROS1 gene mutation. Methods: We selected pleural effusion cell blocks from 41 patients diagnosed with lung adenocarcinoma in the First Affiliated Hospital of Wenzhou Medical University from January 2017 to December 2021. The conventional cell smears and cell blocks were used for pathological HE staining, and NGS and ARMS methods were used for EGFR/ALK/ROS1 gene mutation detection, respectively. Results: The sensitivity of conventional smear was 90.2% and the false negative rate was 9.8%. The diagnostic sensitivity of pleural fluid cell blocks was 100%, and the false negative rate was 0. In the cell smears of malignant pleural effusion (MPE), the overall mutation rate of EGFR/ALK/ROS1 was 70.7% (29/41) and the EGFR mutation rate was 61.0% (25/41); ALK fusion gene detection rate was 7.3% (3/41); ROS1 fusion gene detection rate was 14.6% (6/41). In the cell blocks of MPE, the overall mutation rate of EGFR/ALK/ROS1 was 73.2% (30/41); the EGFR mutation rate was 68.3% (28/41); the ALK fusion gene detection rate was 2.4% (1/41); the ROS1 fusion gene detection rate was 4.9% (2/41). In addition, EGFR/ALK/ROS1mutation-positive patients tested by both methods had increased overall survival rate, progression-free survival rate and disease control rate, compared with those without mutations. Conclusion: Compared with pleural effusion cell smear, pleural effusion cell block method has a higher positive detection rate, which can be used to guidepathological diagnosis and molecular/genetic testing for targeted therapy.