Department of Medical Oncology, Royal Marsden Hospital, London, UK.
Eur J Cancer. 2012 Jan;48(1):61-7. doi: 10.1016/j.ejca.2011.09.022. Epub 2011 Oct 27.
EGFR screening requires good quality tissue, sensitivity and turn-around time (TAT). We report our experience of routine screening, describing sample type, TAT, specimen quality (cellularity and DNA yield), histopathological description, mutation result and clinical outcome.
Non-small cell lung cancer (NSCLC) sections were screened for EGFR mutations (M+) in exons 18-21. Clinical, pathological and screening outcome data were collected for year 1 of testing. Screening outcome alone was collected for year 2.
In year 1, 152 samples were tested, most (72%) were diagnostic. TAT was 4.9 days (95%confidence interval (CI)=4.5-5.5). EGFR-M+ prevalence was 11% and higher (20%) among never-smoking women with adenocarcinomas (ADCs), but 30% of mutations occurred in current/ex-smoking men. EGFR-M+ tumours were non-mucinous ADCs and 100% thyroid transcription factor (TTF1+). No mutations were detected in poorly differentiated NSCLC-not otherwise specified (NOS). There was a trend for improved overall survival (OS) among EGFR-M+ versus EGFR-M- patients (median OS=78 versus 17 months). In year 1, test failure rate was 19%, and associated with scant cellularity and low DNA concentrations. However 75% of samples with poor cellularity but representative of tumour were informative and mutation prevalence was 9%. In year 2, 755 samples were tested; mutation prevalence was 13% and test failure only 5.4%. Although samples with low DNA concentration (<2 ng/μL) had more test failures (30% versus 3.9% for [DNA]>2.2 ng/μL), the mutation rate was 9.2%.
Routine epidermal growth factor receptor (EGFR) screening using diagnostic samples is fast and feasible even on samples with poor cellularity and DNA content. Mutations tend to occur in better-differentiated non-mucinous TTF1+ ADCs. Whether these histological criteria may be useful to select patients for EGFR testing merits further investigation.
表皮生长因子受体（EGFR）的筛选需要高质量的组织、敏感性和周转时间（TAT）。我们报告了常规筛选的经验，描述了样本类型、TAT、标本质量（细胞数量和 DNA 产量）、组织病理学描述、突变结果和临床结局。
对非小细胞肺癌（NSCLC）切片进行 EGFR 外显子 18-21 突变（M+）的筛选。收集了临床、病理和筛选结果数据，用于检测的第 1 年；第 2 年仅收集了筛选结果。
第 1 年，共检测了 152 个样本，其中大多数（72%）为诊断性样本。TAT 为 4.9 天（95%置信区间（CI）=4.5-5.5）。在从不吸烟的女性腺癌（ADC）中，EGFR-M+的患病率较高（20%），但在当前/曾吸烟的男性中，30%的突变发生。EGFR-M+肿瘤为非黏液性 ADC，且 100%甲状腺转录因子（TTF1+）阳性。未在低分化非小细胞肺癌-非特指型（NOS）中检测到突变。在 EGFR-M+与 EGFR-M-患者中，总体生存率（OS）有改善趋势（中位 OS=78 与 17 个月）。在第 1 年，检测失败率为 19%，与细胞数量少和 DNA 浓度低有关。然而，75%的细胞数量少但有代表性的肿瘤样本具有信息性，突变率为 9%。在第 2 年，共检测了 755 个样本；突变率为 13%，检测失败率仅为 5.4%。尽管 DNA 浓度低（<2 ng/μL）的样本检测失败率较高（30%，相比之下，[DNA]>2.2 ng/μL 的样本检测失败率为 3.9%），但突变率为 9.2%。
使用诊断性样本进行常规表皮生长因子受体（EGFR）筛选快速且可行，即使是在细胞数量和 DNA 含量少的样本中也是如此。突变倾向于发生在分化较好的非黏液性 TTF1+ ADC 中。这些组织学标准是否有助于选择进行 EGFR 检测的患者，值得进一步研究。
