Preexisting interstitial lung disease is inversely correlated to tumor epidermal growth factor receptor mutation in patients with lung adenocarcinoma

Fujimoto, Daichi; Tomii, Keisuke; Otoshi, Takehiro; Kawamura, Takahisa; Tamai, Ken; Takeshita, Junpei; Tanaka, Kosuke; Matsumoto, Takeshi; Monden, Kazuya; Nagata, Kazuma; Otsuka, Kyoko; Nakagawa, Atsushi; Hata, Akito; Tachikawa, Ryo; Otsuka, Kojiro; Hamakawa, Hiroshi; Katakami, Nobuyuki; Takahashi, Yutaka; Imai, Yukihiro

doi:10.1016/j.lungcan.2013.01.017

Cited by 31 publications

(30 citation statements)

References 39 publications

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“…One of the explanations of this marked difference could be due to that EGFR -mutant lung cancer is much more common among non-smokers 24 . In their study, the diagnosis of interstitial lung disease was based on clinical features, pretreatment chest CT results, and histological findings 2 . The prevalence of 9.7% among non- EGFR mutant patients is similar to the prevalence of ILA in our study.…”

Section: Discussionmentioning

confidence: 99%

“…Interstitial lung diseases, characterized by lung parenchymal damages due to various patterns of inflammation and fibrosis, were shown to be associated with the development of lung cancer, presumably because inflammation and fibrosis give rise to genetic damage which lead to lung parenchymal carcinogenesis and ultimately to cancer 2-6 . Interstitial lung diseases are also associated with smoking, which is one of the most clearly established risk factors and continued smoking is associated with shorter survival in patients with lung cancer 3, 4, 7-9 .…”

Section: Introductionmentioning

confidence: 99%

“…Interstitial lung diseases are also associated with smoking, which is one of the most clearly established risk factors and continued smoking is associated with shorter survival in patients with lung cancer 3, 4, 7-9 . Some prior reports have identified the similarities between the pathogenesis of interstitial lung diseases and smoking-related carcinogenesis, in the aspects of oxidative stress, mutagenesis, angiogenesis, and epithelial to mesenchymal transformation 2, 10, 11 . It is also well established that interstitial lung diseases may be exacerbated in lung cancer patients after local or systemic therapy which can adversely impact the clinical outcome 12-15 .…”

Section: Introductionmentioning

confidence: 99%

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Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

Nishino

Cardarella

Dahlberg

et al. 2015

European Journal of Radiology

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Objective Interstitial lung diseases are associated with increased risk of lung cancer. The prevalence of ILA at diagnosis of advanced non-small-cell lung cancer (NSCLC) and its impact on overall survival (OS) remain to be investigated. Materials and Method The study included 120 treatment-naïve stage IV NSCLC patients (53 males, 67 females). ILA was scored on CT prior to any systemic therapy using a 4-point scale [0=no evidence of ILA, 1=equivocal for ILA, 2=suspicious for ILA, 3=ILA] by a sequential reading method previously reported. ILA scores of 2 or 3 indicated the presence of ILA. Results ILA was present in 17 patients (14%) with advanced NSCLC prior to any treatment (score3:n=2, score2:n=15). These 17 patients were significantly older (median age: 69 vs. 63, p=0.04) and had a heavier smoking history (median: 40 vs. 15.5 pack-year, p=0.003) than those with ILA score 0 or 1. Higher ILA scores were associated with shorter OS (p=0.001). Median OS of the 17 patients with ILA was 7.2 months [95%CI: 2.9-9.4] compared to 14.8 months [95%CI: 11.1-18.4] in patients with ILA score 0 or 1 (p=0.002). In a multivariate model, the presence of ILA remained significant for increased risk for death (HR=2.09, p=0.028) after adjusting for first-line systemic therapy (chemotherapy, p<0.001; TKI, p<0.001; each compared to no therapy) and pack years of smoking (p=0.40). Conclusion Radiographic ILA was present in 14% of treatment-naïve advanced NSCLC patients. Higher ILA scores were associated with shorter OS, indicating that ILA could be a marker of shorter survival in advanced NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

Nishino

Cardarella

Dahlberg

et al. 2015

European Journal of Radiology

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“…Nevertheless, it should be underlined that a relation subsists between NSCLC associated with ILD and EGFR mutations [17], [18], [19]. Indeed, it has been reported that EGFR mutation is rare in Asian patients with ILD and lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Activation of Oncogenic Pathways in Idiopathic Pulmonary Fibrosis

Stella

Inghilleri

Pignochino

et al. 2014

Translational Oncology

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Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia of unknown cause. The most recent hypotheses on IPF pathogenesis suggest a central role of epithelial cell damage, followed by a dysregulated molecular cross talk between epithelial cells and fibroblasts. Thus, IPF progression has often been assimilated to that of cancer, and several signaling patterns appear to be disrupted in both diseases. Here, we analyze the expression in an IPF series of a panel of molecules, which are known to play a role in tumorigenic process. Our findings, although preliminary, reveal that IPF landscape is enriched in neoplastic potential expressed in a context of complex genomic polyclonality and cellular heterogeneity. These results provide a rationale for further investigations aimed to exploit—in a similar fashion to cancer—targeted therapies for a “precision medicine” approach to IPF.

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“…Recent studies have showed an inverse relationship between the presence of interstitial lung disease and EGFR mutations in associated lung tumors 45,46. However, unlike our study, these studies did not specifically evaluate the role of SRIF in cancer progression, as both smokers and nonsmokers and patients with multiple subtypes of interstitial fibrosis were included in these studies.…”

Section: Discussionmentioning

confidence: 79%

Pulmonary adenocarcinoma mutation profile in smokers with smoking-related interstitial fibrosis

Primiani¹,

Dias‐Santagata²,

Iafrate³

et al. 2014

COPD

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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.

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Preexisting interstitial lung disease is inversely correlated to tumor epidermal growth factor receptor mutation in patients with lung adenocarcinoma

Cited by 31 publications

References 39 publications

Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

Interstitial lung abnormalities in treatment-naïve advanced non-small-cell lung cancer patients are associated with shorter survival

Activation of Oncogenic Pathways in Idiopathic Pulmonary Fibrosis

Pulmonary adenocarcinoma mutation profile in smokers with smoking-related interstitial fibrosis

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