DeMaio Andrew, Clarke Jeffrey M, Dash Rajesh, Sebastian Siby, Wahidi Momen M, Shofer Scott L, Cheng George Z, Li Xuechan, Wang Xiaofei, Mahmood Kamran
Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, New York University, NY.
Department of Medicine, Division of Medical Oncology.
J Bronchology Interv Pulmonol. 2019 Apr;26(2):96-101. doi: 10.1097/LBR.0000000000000534.
Pleural fluid can be used to assess targetable mutations in patients with lung adenocarcinoma. The primary objective of this study was to assess the yield of pleural fluid cytology for targetable oncogenic mutations (EGFR, KRAS, BRAF, ALK, and ROS1 gene rearrangements). We also assessed pleural fluid volume necessary for molecular testing.
Retrospective review was performed of 134 consecutive patients with lung adenocarcinoma associated malignant pleural effusions. EGFR and KRAS testing was done using PCR amplification followed by DNA sequencing, or next generation sequencing in more recent cases that included BRAF assessment. Fluorescence in situ hybridization employing break-apart probes was used to test for ALK and ROS1 rearrangements.
Mutation analysis on pleural fluid cell-block was performed on 56 patients. It was adequate for complete analysis ordered including EGFR, KRAS, BRAF, ALK, and ROS1 rearrangements on 40 (71.4%) samples. For individual mutations, EGFR testing was possible in 38 of 49 (77.6%); KRAS 22 of 28 (78.6%); BRAF 10 of 13 (76.9%), ALK gene rearrangement 42 of 51 (82.4%) and ROS1 gene rearrangement in 21 of 28 (75%) pleural fluid specimens. The analysis was satisfactory in 13 of 19 (68.4%) samples with ≤100 mL versus 27 of 37 (72.9%) with >100 mL of fluid tested (P-value=0.7).
Genetic mutation analysis can be performed on malignant pleural effusions secondary to lung adenocarcinoma, independent of fluid volume.
胸腔积液可用于评估肺腺癌患者的可靶向突变。本研究的主要目的是评估胸腔积液细胞学检查对可靶向致癌突变（表皮生长因子受体[EGFR]、 Kirsten 大鼠肉瘤病毒癌基因[KRAS]、 B-Raf原癌基因[BRAF]、间变性淋巴瘤激酶[ALK]和ROS1基因重排）的检出率。我们还评估了分子检测所需的胸腔积液量。
对134例连续的伴有恶性胸腔积液的肺腺癌患者进行回顾性研究。EGFR和KRAS检测采用聚合酶链反应（PCR）扩增后进行DNA测序，或在包括BRAF评估的近期病例中采用新一代测序。采用断裂分离探针的荧光原位杂交技术检测ALK和ROS1重排。
对56例患者的胸腔积液细胞块进行了突变分析。40份（71.4%）样本足以进行包括EGFR、KRAS、BRAF、ALK和ROS1重排在内的完整分析。对于单个突变，49份样本中有38份（77.6%）可进行EGFR检测；28份中有22份（78.6%）可进行KRAS检测；13份中有10份（76.9%）可进行BRAF检测；51份胸腔积液样本中有42份（82.4%）可进行ALK基因重排检测；28份中有21份（75%）可进行ROS1基因重排检测。检测液体量≤100ml 的19份样本中有13份（68.4%）分析结果令人满意，而检测液体量>100ml 的37份样本中有27份（72.9%）分析结果令人满意（P值=0.7）。
继发于肺腺癌的恶性胸腔积液可进行基因突变分析，与液体量无关。
