Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Department of Pathology, Royal Columbian Hospital, New Westminster, British Columbia, Canada.
Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
J Thorac Oncol. 2014 Jul;9(7):947-956. doi: 10.1097/JTO.0000000000000196.
Epidermal growth factor receptor (EGFR) mutation testing has become critical in the treatment of patients with advanced non-small-cell lung cancer. This study involves a large cohort and epidemiologically unselected series of EGFR mutation testing for patients with nonsquamous non-small-cell lung cancer in a North American population to determine sample-related factors that influence success in clinical EGFR testing.
Data from consecutive cases of Canadian province-wide testing at a centralized diagnostic laboratory for a 24-month period were reviewed. Samples were tested for exon-19 deletion and exon-21 L858R mutations using a validated polymerase chain reaction method with 1% to 5% detection sensitivity.
From 2651 samples submitted, 2404 samples were tested with 2293 samples eligible for analysis (1780 histology and 513 cytology specimens). The overall test-failure rate was 5.4% with overall mutation rate of 20.6%. No significant differences in the failure rate, mutation rate, or mutation type were found between histology and cytology samples. Although tumor cellularity was significantly associated with test-success or mutation rates in histology and cytology specimens, respectively, mutations could be detected in all specimen types. Significant rates of EGFR mutation were detected in cases with thyroid transcription factor (TTF)-1-negative immunohistochemistry (6.7%) and mucinous component (9.0%).
EGFR mutation testing should be attempted in any specimen, whether histologic or cytologic. Samples should not be excluded from testing based on TTF-1 status or histologic features. Pathologists should report the amount of available tumor for testing. However, suboptimal samples with a negative EGFR mutation result should be considered for repeat testing with an alternate sample.
表皮生长因子受体（EGFR）突变检测已成为治疗晚期非小细胞肺癌患者的关键。本研究涉及对北美人群中非小细胞肺癌患者进行大规模、未经选择的 EGFR 突变检测系列，以确定影响临床 EGFR 检测成功率的与样本相关因素。
对 24 个月内在集中诊断实验室进行的加拿大全省范围内的连续病例数据进行了回顾。使用经验证的聚合酶链反应方法（检测灵敏度为 1%至 5%）检测外显子 19 缺失和外显子 21 L858R 突变。
在 2651 个提交的样本中，有 2404 个进行了测试，有 2293 个样本符合分析条件（1780 个组织学和 513 个细胞学标本）。总体测试失败率为 5.4%，总体突变率为 20.6%。组织学和细胞学标本之间的失败率、突变率或突变类型无显著差异。尽管组织学和细胞学标本中肿瘤细胞密度与检测成功率或突变率显著相关，但所有标本类型均能检测到突变。甲状腺转录因子（TTF）-1 免疫组织化学阴性（6.7%）和黏液成分（9.0%）的病例中，均检测到显著的 EGFR 突变率。
应尝试在任何标本（组织学或细胞学）中进行 EGFR 突变检测。不应根据 TTF-1 状态或组织学特征将标本排除在检测之外。病理学家应报告可供检测的肿瘤量。然而，应考虑对 EGFR 突变阴性的亚最佳样本进行重复检测，或采用其他样本进行检测。
