基于细胞学的非小细胞肺癌恶性胸腔积液表皮生长因子受体突变检测标本分类

Cytology-Based Specimen Triage for Epidermal Growth Factor Receptor Mutation Testing of Malignant Pleural Effusions in Non-Small Cell Lung Cancer.

作者信息

Chiang Chi-Lu, Shen Chia-I, Huang Hsu-Ching, Chang Han-Jhih, Huang Yu-Ting, Chiu Chao-Hua

机构信息

Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.

出版信息

Front Oncol. 2022 Jan 24;12:810124. doi: 10.3389/fonc.2022.810124. eCollection 2022.

DOI:10.3389/fonc.2022.810124

PMID:35141163

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8819005/

Abstract

INTRODUCTION

Malignant pleural effusions are common in non-small cell lung cancer (NSCLC). Molecular testing is among the most critical steps in the management of patients with advanced NSCLC. However, the optimal approach for epidermal growth factor receptor (EGFR) mutation testing in such effusion samples remains unclear.

METHODS

We prospectively collected effusion samples from patients with EGFR-mutant NSCLC. Following sample centrifugation, genomic DNA and cell-free DNA were respectively extracted from the sediment and supernatants. EGFR mutation was detected through a real-time PCR assay.

RESULTS

A total of 108 effusions from 78 patients were examined, with 12 and 96 obtained before and after EGFR tyrosine kinase inhibitor treatment, respectively. Carcinoma cells or atypical cells were identified in 73 effusions (67.6%). EGFR mutations were detected in 86 (79.6%) sediment and 84 (77.8%) supernatant samples. Among the effusions with positive cytological findings, the EGFR mutation detection rates were 95.9% (70/73) and 86.3% (63/73) in the sediment and supernatants, respectively. Among the effusions with negative cytological findings, the corresponding detection rates were 45.7% (16/35) and 60% (21/35), respectively. Current clinical practice is to arrange EGFR mutation testing only for sediment from cytologically positive effusions. Through the proposed cytology-based specimen triage, wherein sediment and supernatants with positive and negative cytological findings, respectively, are tested, the detection rate was increased from 64.8% (70/108) to 84.3% (91/108). At half of the cost, this strategy provided a detection rate only slightly lower than the rate in a combined test of all the sediment and supernatants (87.0%, 94/108).

CONCLUSIONS

The separate extraction of DNA from sediment and supernatants obtained from centrifuged effusion samples can improve the overall EGFR mutation detection rate. The present cytology-based specimen triage is an efficient strategy for EGFR mutation testing in patients with EGFR-mutant NSCLC.

摘要

引言

恶性胸腔积液在非小细胞肺癌（NSCLC）中很常见。分子检测是晚期NSCLC患者管理中最关键的步骤之一。然而，此类积液样本中表皮生长因子受体（EGFR）突变检测的最佳方法仍不明确。

方法

我们前瞻性地收集了EGFR突变型NSCLC患者的积液样本。样本离心后，分别从沉淀物和上清液中提取基因组DNA和游离DNA。通过实时PCR检测EGFR突变。

结果

共检测了78例患者的108份积液，其中12份在EGFR酪氨酸激酶抑制剂治疗前获得，96份在治疗后获得。73份积液（67.6%）中发现癌细胞或非典型细胞。沉淀物样本中86份（79.6%）和上清液样本中84份（77.8%）检测到EGFR突变。在细胞学检查结果为阳性的积液中，沉淀物和上清液的EGFR突变检测率分别为95.9%（70/73）和86.3%（63/73）。在细胞学检查结果为阴性的积液中，相应的检测率分别为45.7%（16/35）和60%（21/35）。目前的临床实践是仅对细胞学检查阳性积液的沉淀物进行EGFR突变检测。通过提出的基于细胞学的样本分类方法，即分别对细胞学检查结果为阳性和阴性的沉淀物和上清液进行检测，检测率从64.8%（70/108）提高到84.3%（91/108）。以一半的成本，该策略提供的检测率仅略低于所有沉淀物和上清液联合检测的率（87.0%，94/108）。