title: Pulmonary adenocarcinoma mutation profile in smokers with smoking-related interstitial fibrosis.
abstract: Cigarette smoking is an established cause of lung cancer. However, pulmonary fibrosis is also an independent risk factor for the development of lung cancer. Smoking-related interstitial fibrosis (SRIF) has recently been reported. We hypothesized that adenocarcinomas in lungs with SRIF might show distinct molecular changes and examined the molecular phenotype of 168 resected lung adenocarcinomas in lungs with and without SRIF. The diagnosis of SRIF was determined by histological examination, based on the presence of alveolar septal thickening, due to pauci-inflamed, hyalinized, "ropy" collagen, in areas of lung greater than 1 cm away from the tumor. Tumors were concomitantly examined genotypically for mutations in genes frequently altered in cancer, including EGFR and KRAS, by SNaPshot and by fluorescence in situ hybridization for possible ALK rearrangements. Fluorescence in situ hybridization for ROS1 rearrangement (n=36) and/or MET amplification (n=31) were performed when no mutation was identified by either SNaPshot or ALK analysis. Sixty-five cases (38.7%) showed SRIF, which was distributed in all lobes of the lungs examined. No differences were observed in sex, average age, or smoking history in patients with and without SRIF. There was no difference in either the percent or types of adenocarcinoma genetic mutations in patients with SRIF versus those without. This data suggests that SRIF does not represent an independent risk factor for the development of the major known and targeted mutations seen in pulmonary adenocarcinoma. However, additional research is required to investigate the potential significance of SRIF in the pathogenesis of lung cancer.
authors.affiliation: Pathology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Primiani
authors.affiliation: Pathology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Dora
authors.initials: D
authors.lastname: Dias-Santagata
authors.affiliation: Pathology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: A John
authors.initials: AJ
authors.lastname: Iafrate
authors.affiliation: Pathology Service, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA ; Pulmonary Medicine/Critical Care Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Kradin
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D004252:DNA Mutational Analysis; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017563:Lung Diseases, Interstitial / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D049268:Positron-Emission Tomography; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D014057:Tomography, X-Ray Computed
chemical_list: D014408:Biomarkers, Tumor
keywords: SRIF; cancer; lung; smoking