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

Alice Guyard,Hélène Blons,Marie-Pierre Debray,Yves Castier,Gérard Zalcman,Nathalie Théou-Anton,Laure Gibault,Bruno Crestani,Aurélie Cazes,Pierre Mordant,Claire Danel

doi:10.1186/s12931-017-0605-y

Abstract

BackgroundPrimitive 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).MethodsThirty-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.ResultsSquamous 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%.ConclusionsThis 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.

Highlights

Primitive lung cancers developed on lung fibroses are both diagnostic and therapeutic challenges
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
The aim of this study was to describe a retrospective cohort of lung cancers developed on idiopathic pulmonary fibrosis (IPF) and other pulmonary fibroses, and to search for molecular alterations that could either represent therapeutic targets or specific oncogenic pathways in these interstitial lung diseases (ILD)

Summary

Introduction

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). An increased incidence of lung cancer has been described in IPF patients, with a significantly adverse impact on survival [2,3,4,5,6]. Lung cancer in IPF patients is a therapeutic challenge as both surgery and radiotherapy are limited by lung dysfunction and are at high risk of respiratory exacerbation. Over the past decade a better knowledge of lung cancer biology led to major changes in the management

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