Medical Oncology

, 33:119 | Cite as

How strong is the association between IPF and lung cancer? An answer from airway’s DNA

  • G. E. CarpagnanoEmail author
  • D. Lacedonia
  • P. Soccio
  • I. Caccavo
  • G. Patricelli
  • M. P. Foschino Barbaro
Short Communication


Idiopathic pulmonary fibrosis is a chronic progressive disease of lung interstitium of unknown etiology with poor prognosis. In patients with IPF, the incidence of lung cancer is much higher than that in the general population. The identification of noninvasive biomarkers for early diagnosis of IPF is of great relevance in consideration of the management of these patients. Among the noninvasive omic markers, an increasing interest has been directed toward the study of genetic alterations of microsatellites (MAs) in exhaled breath condensate (EBC). The aim of this preliminary study was to investigate the MAs, located in chromosomal regions 8p21.3–q11.1 and 17q11.2–q21, that harbor tumor suppressor genes, in EBC and in the paired whole blood (WB) of IPF patients. Eleven IPF patients were compared with 10 healthy control subjects. All subjects underwent collection of the EBC and WB. The EBC was collected using a condenser. Four microsatellite markers (THRA1, D17S579, D17S250 and D8S137) were used for the analysis of MAs. The EBC-DNA and WB-DNA were amplified by PCR; PCR products were analyzed using the ABI Prism 310 DNA. Microsatellite alterations were found in 58.82 % of EBC-DNA and 12.50 % of WB-DNA in patients with IPF (p < 0.01). None of the healthy subjects exhibited MAs in the studied markers. Our findings suggest that these genetic alterations, studied in EBC, may play an important role in the complex genetic basis of IPF. Since these MAs are frequently detected in cancer, they might explain the higher relative risk of tumorigenesis in this disease.


Microsatellite alterations Lung cancer IPF EBC 


Author contributions

GEC and PS designed the study; DL, PS, IC and GP contributed to the clinical and laboratory work for the study; GEC took responsibility for the integrity of the data in the study and the accuracy of the data analysis; GEC and PS analyzed the data and wrote paper; GEC, DL and MPFB contributed to critical review and final approval of the manuscript. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 2011;183:788–824.CrossRefPubMedGoogle Scholar
  2. 2.
    Vancheri C, Failla M, Crimi N, Raghu G. Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology. Eur Respir J. 2010;35:496–504.CrossRefPubMedGoogle Scholar
  3. 3.
    Vancheri C. Common pathways in idiopathic pulmonary fibrosis and cancer. Eur Respir Rev. 2013;22:265–72.CrossRefPubMedGoogle Scholar
  4. 4.
    Sourvinos G, Kiaris H, Tsikkinis A, Vassilaros S, Spandidos DA. Microsatellite instability and loss of heterozygosity in primary breast tumours. Tumour Biol. 1997;18:157–66.CrossRefPubMedGoogle Scholar
  5. 5.
    Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature. 1993;363:558–61.CrossRefPubMedGoogle Scholar
  6. 6.
    Field JK, Kiaris H, Howard P, Vaughan ED, Spandidos DA, Jones AS. Microsatellite instability in squamous cell carcinoma of the head and neck. Br J Cancer. 1995;71:1065–9.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Froudarakis ME, Sourvinos G, Fournel P, Bouros D, Vergnon JM, Spandidos DA, Siafakas NM. Microsatellite instability and loss of heterozygosity at chromosomes 9 and 17 in non-small cell lung cancer. Chest. 1998;113:1091–4.CrossRefPubMedGoogle Scholar
  8. 8.
    Carpagnano GE, Foschino-Barbaro MP, Resta O, Gramiccioni E, Carpagnano F. Endothelin-1 is increased in the breath condensate of patients with non-small cell lung cancer. Oncology. 2004;66:180–4.CrossRefPubMedGoogle Scholar
  9. 9.
    Carpagnano GE, Barnes PJ, Geddes DM, Hodson ME, Kharitonov SA. Increased leukotriene B4 and interleukin-6 in exhaled breath condensate in cystic fibrosis. Am J Respir Crit Care Med. 2003;167:1109–12.CrossRefPubMedGoogle Scholar
  10. 10.
    Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro MP, Gramiccioni E, Barnes PJ. Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnoea patients. Chest. 2002;122:1162–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro MP, Gramiccioni E, Barnes PJ. IL-6 is increased in breath condensate of smokers. Eur Respir J. 2003;21:589–93.CrossRefPubMedGoogle Scholar
  12. 12.
    Carpagnano GE, Barnes PJ, Francis J, Wilson N, Bush A, Kharitonov SA. Breath condensate pH in children with CF and asthma: A new noninvasive marker of airway inflammation? Chest. 2004;125:2005–10.CrossRefPubMedGoogle Scholar
  13. 13.
    Carpagnano GE, Kharitonov SA, Resta O, Foschino-Barbaro MP, Gramiccioni E, Barnes PJ. 8-isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by CPAP therapy. Chest. 2003;124:1386–92.CrossRefPubMedGoogle Scholar
  14. 14.
    Lerebours F, Olschwang S, Thuille B, Schmitz A, Fouchet P, Buecher B, Martinet N, Galateau F, Thomas G. Fine deletion mapping of chromosome 8p in non-small-cell lung carcinoma. Int J Cancer. 1999;81:854–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Fong KM, Kida Y, Zimmerman PV, Ikenaga M, Smith PJ. Loss of heterozygosity frequently affects chromosome 17q in non-small cell lung cancer. Cancer Res. 1995;55:4268–72.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • G. E. Carpagnano
    • 1
    Email author
  • D. Lacedonia
    • 1
  • P. Soccio
    • 1
  • I. Caccavo
    • 1
  • G. Patricelli
    • 1
  • M. P. Foschino Barbaro
    • 1
  1. 1.Department of Medical and Surgical Sciences, Institute of Respiratory DiseasesUniversity of FoggiaFoggiaItaly

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