Guyard Alice, Danel Claire, Théou-Anton Nathalie, Debray Marie-Pierre, Gibault Laure, Mordant Pierre, Castier Yves, Crestani Bruno, Zalcman Gérard, Blons Hélène, Cazes Aurélie
Département de Pathologie, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, 46 rue Henri Huchard, 75018, Paris, France.
Département de Génétique, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, 46 rue Henri Huchard, 75018, Paris, France.
Respir Res. 2017 Jun 15;18(1):120. doi: 10.1186/s12931-017-0605-y.
Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges. Their incidence may increase with new more efficient lung fibrosis treatments. Our aim was to describe a cohort of lung cancers associated with idiopathic pulmonary fibrosis (IPF) and other lung fibrotic disorders (non-IPF), and to characterize their molecular alterations using immunohistochemistry and next-generation sequencing (NGS).
Thirty-one cancer samples were collected from 2001 to 2016 in two French reference centers for pulmonary fibrosis - 18 for IPF group and 13 for non-IPF group. NGS was performed using an ampliseq panel to analyze hotspots and targeted regions in 22 cancer-associated genes. ALK, ROS1 and PD-L1 expressions were assessed by immunohistochemistry.
Squamous cell carcinoma was the most frequent histologic subtype in the IPF group (44%), adenocarcinoma was the most frequent subtype in the non-IPF group (62%). Forty-one mutations in 13 genes and one EGFR amplification were identified in 25 samples. Two samples had no mutation in the selected panel. Mutations were identified in TP53 (n = 20), MET (n = 4), BRAF (n = 3), FGFR3, PIK3CA, PTEN, STK11 (n = 2), SMAD4, CTNNB1, DDR2, ERBB4, FBXW7 and KRAS (n = 1) genes. No ALK and ROS1 expressions were identified. PD-L1 was expressed in 10 cases (62%) with only one (6%) case >50%.
This extensive characterization of lung fibrosis-associated cancers evidenced molecular alterations which could represent either potential therapeutic targets either clues to the pathophysiology of these particular tumors. These findings support the relevance of large molecular characterization of every lung fibrosis-associated cancer.
发生于肺纤维化基础上的原发性肺癌在诊断和治疗方面均具有挑战性。随着新型更有效的肺纤维化治疗方法的出现，其发病率可能会增加。我们的目的是描述一组与特发性肺纤维化（IPF）及其他肺纤维化疾病（非IPF）相关的肺癌，并通过免疫组织化学和下一代测序（NGS）对其分子改变进行特征分析。
2001年至2016年期间，在法国两个肺纤维化参考中心收集了31份癌症样本，其中IPF组18份，非IPF组13份。使用扩增子测序面板进行NGS，以分析22个癌症相关基因的热点和靶向区域。通过免疫组织化学评估ALK、ROS1和PD-L1的表达。
鳞状细胞癌是IPF组中最常见的组织学亚型（44%），腺癌是非IPF组中最常见的亚型（62%）。在25个样本中鉴定出13个基因的41个突变和1个EGFR扩增。2个样本在所选面板中未发现突变。在TP53（n = 20）、MET（n = 4）、BRAF（n = 3）、FGFR3、PIK3CA、PTEN、STK11（n = 2）、SMAD4、CTNNB1、DDR2、ERBB4、FBXW7和KRAS（n = 1）基因中发现了突变。未发现ALK和ROS1表达。10例（62%）表达PD-L1，其中仅1例（6%）>50%。
对肺纤维化相关癌症的这种广泛特征分析证实了分子改变，这些改变可能代表潜在的治疗靶点或这些特殊肿瘤病理生理学的线索。这些发现支持对每例肺纤维化相关癌症进行大规模分子特征分析的相关性。
