Skip to main content

Advertisement

SpringerLink
Log in

Bronchiolar columnar cell dysplasia—genetic analysis of a novel preneoplastic lesion of peripheral lung

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Atypical adenomatous hyperplasia is the only known precursor lesion of lung adenocarcinomas (ACs) so far. Here, we describe a new dysplastic lesion in the bronchioles of peripheral lung for which we propose the name bronchiolar columnar cell dysplasia (BCCD). Eight of fourteen BCCDs were successfully analyzed by means of comparative genomic hybridization (CGH). The average number of chromosomal aberrations was 2.6 in BCCD and 14.7 in concomitant AC. Among the aberrations were losses of 3p, 9, 13, 14 and gains of 1q, 17, 19q and 20q. Summarizing our data from morphological and genetic analysis, we conclude that BCCD is a preneoplasia of the bronchiolar epithelium and most probably represents an additional precursor lesion of lung adenocarcinomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.
Fig. 6. a

Similar content being viewed by others

References

  1. Bostwick DG (2000) Prostatic intraepithelial neoplasia. Curr Urol Rep 1:65–70

    CAS  PubMed  Google Scholar 

  2. Colby TV, Wistuba II, Gazdar A (1998) Precursors to pulmonary neoplasia. Adv Anat Pathol 5:205–215

    CAS  PubMed  Google Scholar 

  3. Hruban RH, Adsay NV, Albores-Saavedra J, Compton C, Garrett ES, Goodman SN, Kern SE, Klimstra DS, Kloeppel G, Longnecker DS, Luttges J, Offerhaus GJ (2001) Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol 25:579–586

    CAS  PubMed  Google Scholar 

  4. Hubbard R, Venn A, Lewis S, et al (2000) Lung cancer and cryptogenic fibrosing alveolitis. A population-based cohort study. Am J Respir Crit Care Med 161:5–8

    CAS  PubMed  Google Scholar 

  5. Hung J, Kishimoto Y, Sugio K, et al (1995) Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA 273:1908

    CAS  Google Scholar 

  6. Kishimoto Y, Sugio K, Hung JY, et al (1995) Allele-specific loss in chromosome 9p loci in preneoplastic lesions accompanying non-small-cell lung cancers. J Natl Cancer Inst 87:1224–1229

    CAS  PubMed  Google Scholar 

  7. Kitamura H, Kameda Y, Ito T, et al (1999) Atypical adenomatous hyperplasia of the lung. Implications for the pathogenesis of peripheral lung adenocarcinoma. Am J Clin Pathol 111:610–622

    CAS  PubMed  Google Scholar 

  8. Luttges J, Galehdari H, Brocker V, et al (2001) Allelic loss is often the first hit in the biallelic inactivation of the p53 and DPC4 genes during pancreatic carcinogenesis. Am J Pathol 158:1677–1683

    CAS  PubMed  Google Scholar 

  9. Michelland S, Gazzeri S, Brambilla E, et al (1999) Comparison of chromosomal imbalances in neuroendocrine and non-small-cell lung carcinomas. Cancer Genet Cytogenet 114:22–30

    Article  CAS  PubMed  Google Scholar 

  10. Mori M, Rao SK, Popper HH, Cagle PT, Fraire AE (2001) Atypical adenomatous hyperplasia of the lung: a probable forerunner in the development of adenocarcinoma of the lung. Mod Pathol 14:72–84

    CAS  PubMed  Google Scholar 

  11. Petersen I, Bujard M, Petersen S, et al (1997) Patterns of chromosomal imbalances in adenocarcinoma and squamous cell carcinoma of the lung. Cancer Res 57:2331–2335

    CAS  PubMed  Google Scholar 

  12. Petzmann S, Ullmann R, Klemen H, et al (2001) Loss of heterozygosity on chromosome arm 11q in lung carcinoids. Hum Pathol 32:333–338

    Article  CAS  PubMed  Google Scholar 

  13. Samet JM (2000) Does idiopathic pulmonary fibrosis increase lung cancer risk? Am J Respir Crit Care Med 161:1–2

    CAS  PubMed  Google Scholar 

  14. Sanz-Ortega J, Saez MC, Sierra E, et al (2001) 3p21, 5q21, and 9p21 allelic deletions are frequently found in normal bronchial cells adjacent to non-small-cell lung cancer, while they are unusual in patients with no evidence of malignancy. J Pathol 195:429–434

    Article  CAS  PubMed  Google Scholar 

  15. Takayama H, Takakuwa T, Dong Z, et al (2001) Fas gene mutations in prostatic intraepithelial neoplasia and concurrent carcinoma: analysis of laser capture microdissected specimens. Lab Invest 81:283–288

    CAS  PubMed  Google Scholar 

  16. Thiberville L, Payne P, Vielkinds J, et al (1995) Evidence of cumulative gene losses with progression of premalignant epithelial lesions to carcinoma of the bronchus. Cancer Res 55:5133–5139

    CAS  PubMed  Google Scholar 

  17. Wistuba, II, Berry J, Behrens C, et al (2000) Molecular changes in the bronchial epithelium of patients with small cell lung cancer. Clin Cancer Res 6:2604–2610

    CAS  PubMed  Google Scholar 

  18. Yamasaki M, Takeshima Y, Fujii S, et al (2000) Correlation between genetic alterations and histopathological subtypes in bronchiolo-alveolar carcinoma and atypical adenomatous hyperplasia of the lung. Pathol Int 50:778–785

    Article  CAS  PubMed  Google Scholar 

  19. Yasuhara K, Mitsumori K, Yoshimura H, et al (1995) Relationship between the development of pulmonary fibrosis and lung tumors in Syrian golden hamsters induced by N-methyl-N-nitrosourethane. Toxicol Pathol 23:551–559

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the support by the Austrian Research Fund (FWF project P14759) and the Styrian Cancer Society Foundation (to HHP). RU and SP were supported by the Austrian National Bank Jubilee Fund (Projects OeNB 7645 and 8454), which is also gratefully acknowledged.

Author information

Authors and Affiliations

  1. Laboratories of Molecular Cytogenetics, Environmental and Respiratory Pathology, Institute of Pathology, Auenbruggerplatz 25, 8036, Graz , Austria

    Reinhard Ullmann, Iris Halbwedl, Susanna Petzmann, Margit Gogg-Kammerer & Helmut H. Popper

  2. Department of Biomedical Science and Oncology, University of Torino, Torino, Italy

    Massimo Bongiovanni, Anna Sapino, Mauro Papotti & Gianni Bussolati

Authors
  1. Reinhard Ullmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Massimo Bongiovanni
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Iris Halbwedl
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susanna Petzmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Margit Gogg-Kammerer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anna Sapino
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mauro Papotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Gianni Bussolati
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Helmut H. Popper
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Helmut H. Popper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ullmann, R., Bongiovanni, M., Halbwedl, I. et al. Bronchiolar columnar cell dysplasia—genetic analysis of a novel preneoplastic lesion of peripheral lung. Virchows Arch 442, 429–436 (2003). https://doi.org/10.1007/s00428-003-0797-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-003-0797-z

Keywords

Search

Navigation