Brioude Geoffrey, Brégeon Fabienne, Trousse Delphine, Flaudrops Christophe, Secq Véronique, De Dominicis Florence, Chabrières Eric, D'journo Xavier-Benoit, Raoult Didier, Thomas Pascal-Alexandre
Service de chirurgie thoracique et des maladies de l'œsophage, Pôle cardio-vasculaire et thoracique, Centre Hospitalo-Universitaire Nord, Assistance publique-Hôpitaux de Marseille, Aix-Marseille université, Marseille, France.
Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, URMITE CNRS 7278 IRD 198 INSERM U1905, IHU Méditerranée Infection, Faculté de Médecine, Aix-Marseille Université, Marseille, France.
PLoS One. 2016 May 26;11(5):e0155449. doi: 10.1371/journal.pone.0155449. eCollection 2016.
Despite recent advances in imaging and core or endoscopic biopsies, a percentage of patients have a major lung resection without diagnosis. We aimed to assess the feasibility of a rapid tissue preparation/analysis to discriminate cancerous from non-cancerous lung tissue.
Fresh sample preparations were analyzed with the Microflex LTTM MALDI-TOF analyzer. Each main reference spectra (MSP) was consecutively included in a database. After definitive pathological diagnosis, each MSP was labeled as either cancerous or non-cancerous (normal, inflammatory, infectious nodules). A strategy was constructed based on the number of concordant responses of a mass spectrometry scoring algorithm. A 3-step evaluation included an internal and blind validation of a preliminary database (n = 182 reference spectra from the 100 first patients), followed by validation on a whole cohort database (n = 300 reference spectra from 159 patients). Diagnostic performance indicators were calculated.
127 cancerous and 173 non-cancerous samples (144 peripheral biopsies and 29 inflammatory or infectious lesions) were processed within 30 minutes after biopsy sampling. At the most discriminatory level, the samples were correctly classified with a sensitivity, specificity and global accuracy of 92.1%, 97.1% and 95%, respectively.
The feasibility of rapid MALDI-TOF analysis, coupled with a very simple lung preparation procedure, appears promising and should be tested in several surgical settings where rapid on-site evaluation of abnormal tissue is required. In the operating room, it appears promising in case of tumors with an uncertain preoperative diagnosis and should be tested as a complementary approach to frozen-biopsy analysis.
尽管近期在成像技术以及核心活检或内镜活检方面取得了进展,但仍有一定比例的患者在未明确诊断的情况下接受了肺大部切除术。我们旨在评估快速组织制备/分析以区分癌性与非癌性肺组织的可行性。
使用Microflex LT™ MALDI-TOF分析仪对新鲜样本制剂进行分析。每个主要参考光谱(MSP)依次纳入数据库。在明确病理诊断后,将每个MSP标记为癌性或非癌性(正常、炎症、感染性结节)。基于质谱评分算法的一致反应数量构建了一种策略。三步评估包括对初步数据库(来自首批100例患者的182个参考光谱)进行内部和盲法验证,随后在整个队列数据库(来自159例患者的300个参考光谱)上进行验证。计算诊断性能指标。
在活检取样后30分钟内处理了127个癌性样本和173个非癌性样本(144个周边活检样本和29个炎症或感染性病变样本)。在最具区分性的水平上,样本分类正确,灵敏度、特异性和总体准确率分别为92.1%、97.1%和95%。
快速MALDI-TOF分析的可行性,再加上非常简单的肺组织制备程序,看起来很有前景,应在需要对异常组织进行快速现场评估的几种手术环境中进行测试。在手术室中,对于术前诊断不确定的肿瘤,它看起来很有前景,应作为冰冻活检分析的补充方法进行测试。