Lozano Maria D, Labiano Tania, Echeveste Jose, Gurpide Alfonso, Martín-Algarra Salvador, Zhang Guili, Sharma Abha, Palma John F
Department of Pathology, Clinical University of Navarra-University of Navarra, Pamplona, Spain.
Cancer Cytopathol. 2015 Apr;123(4):230-6. doi: 10.1002/cncy.21513. Epub 2014 Dec 19.
Molecular testing to determine gene mutation status is now the recommended standard of care for patients with advanced or metastatic Non-small cell lung cancer (NSCLC). Because the majority of patients with NSCLC present with metastatic disease, minimally invasive procedures are necessary for diagnosis, staging, and molecular analysis. However, the resulting samples have perceived limitations in the oncology community, and most commercially available tests have not been validated for these sample types. The current study was undertaken to assess the feasibility of determining epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status in fine-needle aspirates (FNAs) and core-needle biopsies (CNBs) after staining with Papanicolaou or hematoxylin and eosin, respectively.
Gene mutation status was determined in 140 NSCLC tumor samples with proprietary tests for EGFR and KRAS mutations (cobas tests) followed by Sanger sequencing of exons 18 through 21 of the EGFR gene and exon 2 of the KRAS gene. The results were analyzed based on FNA (n = 91) or CNB (n = 49) sampling.
The cobas tests yielded valid results in the majority of FNA and CNB samples for both EGFR (97.9%) and KRAS (93.6%). Moreover, valid results were obtained for 90% of samples that had DNA concentrations below the values recommended by the manufacturer. For samples with valid results from both cobas testing and Sanger sequencing, 95.7% and 93% agreement were observed for EGFR status and KRAS status, respectively.
Gene mutation testing can be successfully performed on cytology and CNB samples, expanding the potential of personalized cancer treatment to patients who have limited tissue samples.
确定基因突变状态的分子检测目前是晚期或转移性非小细胞肺癌（NSCLC）患者推荐的标准治疗方法。由于大多数NSCLC患者就诊时已出现转移性疾病，因此诊断、分期及分子分析需要采用微创方法。然而，肿瘤学界认为由此获得的样本存在局限性，且大多数市售检测方法尚未针对这些样本类型进行验证。本研究旨在评估分别经巴氏染色或苏木精-伊红染色后的细针穿刺抽吸物（FNA）和粗针活检（CNB）中，确定表皮生长因子受体（EGFR）和 Kirsten 大鼠肉瘤病毒癌基因同源物（KRAS）基因突变状态的可行性。
采用针对EGFR和KRAS突变的专有检测方法（cobas检测）对140例NSCLC肿瘤样本的基因突变状态进行测定，随后对EGFR基因的第18至21外显子和KRAS基因的第2外显子进行Sanger测序。根据FNA（n = 91）或CNB（n = 49）采样对结果进行分析。
对于EGFR（97.9%）和KRAS（93.6%），cobas检测在大多数FNA和CNB样本中均产生了有效的结果。此外，DNA浓度低于制造商推荐值的样本中，90%获得了有效的结果。对于cobas检测和Sanger测序均得到有效结果的样本，EGFR状态和KRAS状态的一致性分别为95.7%和93%。
基因突变检测可在细胞学和CNB样本上成功进行，从而将个性化癌症治疗的潜力扩展至组织样本有限的患者。
