Morphologic and molecular study of lung cancers associated with idiopathic pulmonary fibrosis and other pulmonary fibroses

• Published in: Respiratory research Vol. 18; no. 1; p. 120
• Main Authors: Guyard, Alice, Danel, Claire, Théou-Anton, Nathalie, Debray, Marie-Pierre, Gibault, Laure, Mordant, Pierre, Castier, Yves, Crestani, Bruno, Zalcman, Gérard, Blons, Hélène, Cazes, Aurélie
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.06.2017; BioMed Central; BMC
• Subjects: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Amplification; Analysis; Biopsy; Cancer; Care and treatment; Cdc4 protein; Cloning; Cohort Studies; Complications and side effects; Deoxyribonucleic acid; Development and progression; Diagnosis; Diagnostic systems; Disorders; DNA; Epidermal growth factor receptors; ErbB-2 protein; Female; Fibroblast growth factor receptors; Fibrosis; Fibrosis-associated lung cancer; Genes; Group dynamics; Health aspects; Humans; Idiopathic pulmonary fibrosis; Idiopathic Pulmonary Fibrosis - genetics; Idiopathic Pulmonary Fibrosis - pathology; Immunohistochemistry; Incidence; K-Ras protein; Kinases; Lung cancer; Lung diseases; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical prognosis; Middle Aged; Mutation; Next-generation sequencing; p53 Protein; Patients; PD-L1 protein; Pneumonia; Prognosis; PTEN protein; Pulmonary fibrosis; Pulmonary Fibrosis - genetics; Pulmonary Fibrosis - pathology; Retrospective Studies; Risk factors; Smad4 protein; Squamous cell carcinoma; Statistical analysis; Tobacco; Tumors; France; Fibrosis-associated lung cancer; Idiopathic pulmonary fibrosis; Next-generation sequencing
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• 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.