Laboratory of Biochemistry and Genetics, Division of Pneumology, Department of Molecular Medicine, University and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy.
J Cancer Res Clin Oncol. 2013 Aug;139(8):1327-35. doi: 10.1007/s00432-013-1444-y. Epub 2013 May 5.
Knowledge of tumor mutational status has become a priority for effective NSCLC-tailored treatment. NSCLC diagnosis is more often reached through biopsy; thus, there is a clear need to implement for routine tumor molecular profiling on small cytological samples. This work aims to screen and compare the EGFR and KRAS mutational prevalence in fresh tumor cells and in corresponding routinely processed samples derived from trans-thoracic fine-needle aspiration. The latter currently represents the most appropriate diagnostic procedure in case of peripheral lesions, such as adenocarcinomas, which account for almost 40% of all NSCLCs and for the highest EGFR mutational rates.
Two hundred and forty-four patients carrying peripheral lung masses underwent CT-guided aspiration. The obtained material was split, and a part was addressed to conventional histopathological analysis while the remaining one was stored at -20 °C. In case of confirmation of adenocarcinoma, tumor genomic DNA was extracted from both fresh and fixed material, and EGFR and KRAS sequencing was performed.
We identified 136 adenocarcinomas; from 134, we could recover enough material for the study. A full match was demonstrated between EGFR/KRAS mutational prevalences through the two approaches tested. We found EGFR mutations in 13 patients (9.7%); 7 were females and 11 never or former smokers. KRAS mutations occurred in 20 (14.9%) patients. EGFR and KRAS mutations were mutually exclusive.
Mutational screening on fresh cancer cells is an achievable, safe and cost-effective procedure which might allow routinely tumor molecular profiling as powerful integration of conventional histopathological analysis.
肿瘤突变状态的知识已成为制定有效 NSCLC 靶向治疗方案的首要任务。非小细胞肺癌（NSCLC）的诊断通常通过活检获得，因此，非常有必要在小细胞学样本上实施常规肿瘤分子分析。本研究旨在筛选和比较新鲜肿瘤细胞与经胸细针抽吸术（TTNA）获得的常规处理样本中 EGFR 和 KRAS 突变的流行率。后者目前是外周病变（如腺癌）最适合的诊断方法，腺癌占所有 NSCLC 的近 40%，且 EGFR 突变率最高。
244 名患有肺外周肿块的患者接受了 CT 引导下的抽吸术。所获得的标本被分为两部分，一部分用于常规组织病理学分析，另一部分储存在-20°C。在确认腺癌的情况下，从新鲜和固定材料中提取肿瘤基因组 DNA，并进行 EGFR 和 KRAS 测序。
我们鉴定了 136 例腺癌；从 134 例中，我们可以获得足够的研究材料。通过两种方法检测到的 EGFR/KRAS 突变流行率完全一致。我们在 13 名患者（9.7%）中发现了 EGFR 突变，其中 7 名女性，11 名从未吸烟或曾吸烟。20 名患者（14.9%）发生 KRAS 突变。EGFR 和 KRAS 突变是相互排斥的。
对新鲜癌细胞进行突变筛查是一种可行、安全且具有成本效益的方法，它可能使肿瘤分子分析成为常规组织病理学分析的有力补充。
