Skip to main content

Advertisement

SpringerLink
Log in

Stepwise progression of pulmonary adenocarcinoma—clinical and molecular implications

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Stepwise progression of pulmonary adenocarcinoma is described from the viewpoint of both pathology and molecular biology. Pulmonary adenocarcinoma develops to invasive carcinoma through atypical adenomatous hyperplasia, adenocarcinoma in situ and minimally invasive adenocarcinoma. The Noguchi classification is well correlated with this sequential histological progression. On the other hand, in terms of molecular biology, p16 gene inactivation, EGFR mutation and KRAS mutation are early events, and tumors progress to invasive adenocarcinoma as a result of p53 mutation, loss of various chromosomes and other genetic abnormalities.

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
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Travis, W. D., Lubin, J., Ries, L., & Devesa, S. (1996). United States lung carcinoma incidence trends: declining for most histologic types among males, increasing among females. Cancer, 77, 2464–2470.

    Article  PubMed  CAS  Google Scholar 

  2. Valaitis, J., Warren, S., & Gamble, D. (1981). Increasing incidence of adenocarcinoma of the lung. Cancer, 47, 1042–1046.

    Article  PubMed  CAS  Google Scholar 

  3. Travis, W. D., Travis, L. B., & Devesa, S. S. (1995). Lung cancer. Cancer, 75, 191–202.

    Article  PubMed  CAS  Google Scholar 

  4. Travis, W. D., Colby, T. V., Corrin, B., et al. (1999). WHO histological typing of lung and pleural tumors (3rd ed.). Geneva: World Health Organization.

    Google Scholar 

  5. Travis, W. D., Brambilla, E. B., Muller-Hermelink, H. K., & Harris, C. C. (2004). WHO pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARCPress.

    Google Scholar 

  6. Yatabe, Y., Mitsudomi, T., & Takahashi, T. (2002). TTF-1 expression in pulmonary adenocarcinomas. American Journal of Surgical Pathology, 26, 767–773.

    Article  PubMed  Google Scholar 

  7. Nakayama, H., Noguchi, M., Tsuchiya, R., Kodama, T., & Shimosato, Y. (1990). Clonal growth of atypical adenomatous hyperplasia of the lung: cytofluorometric analysis of nuclear DNA content. Modern Pathology, 3, 314–320.

    PubMed  CAS  Google Scholar 

  8. Anami, Y., Matsuno, Y., Yamada, T., et al. (1998). A case of double primary adenocarcinoma of the lung with multiple atypical adenomatous hyperplasia. Pathology International, 48, 634–640.

    Article  PubMed  CAS  Google Scholar 

  9. Noguchi, M., Morikawa, A., Kawasaki, M., et al. (1995). Small adenocarcinoma of the lung. Histologic characteristics and prognosis. Cancer, 75, 2844–2852.

    Article  PubMed  CAS  Google Scholar 

  10. Nakamura, N., Iijima, T., Mase, K., et al. (2004). Phenotypic differences of proliferating fibroblasts in the stroma of lung adenocarcinoma and normal bronchus tissue. Cancer Science, 95, 226–232.

    Article  PubMed  CAS  Google Scholar 

  11. Minami, Y., Matsuno, Y., Iijima, T., et al. (2005). Prognostication of small-sized primary pulmonary adenocarcinomas by histopathological and karyometric analysis. Lung Cancer, 48, 339–348.

    Article  PubMed  Google Scholar 

  12. Suzuki, K., Yokose, T., Yoshida, J., et al. (2000). Prognostic significance of the size of central fibrosis in peripheral adenocarcinoma of the lung. Annals of Thoracic Surgery, 69, 893–897.

    Article  PubMed  CAS  Google Scholar 

  13. Yokose, T., Suzuki, K., Nagai, K., Nishiwaki, Y., Sasaki, S., & Ochiai, A. (2000). Favorable and unfavorable morphological prognostic factors in peripheral adenocarcinoma of the lung 3 cm or less in diameter. Lung Cancer, 29, 179–188.

    Article  PubMed  CAS  Google Scholar 

  14. Sakurai, H., Maeshima, A., Watanabe, S., et al. (2004). Grade of stromal invasion in small adenocarcinoma of the lung: histopathological minimal invasion and prognosis. American Journal of Surgical Pathology, 28, 198–206.

    Article  PubMed  Google Scholar 

  15. Sakamoto, H., Shimizu, J., Horio, Y., et al. (2007). Disproportionate representation of KRAS gene mutation in atypical adenomatous hyperplasia, but even distribution of EGFR gene mutation from preinvasive to invasive adenocarcinomas. Journal of Pathology, 212, 287–294.

    Article  PubMed  CAS  Google Scholar 

  16. Kobayashi, T., Tsuda, H., Noguchi, M., et al. (1990). Association of point mutation in c-Ki-ras oncogene in lung adenocarcinoma with particular reference to cytologic subtypes. Cancer, 66, 289–294.

    Article  PubMed  CAS  Google Scholar 

  17. Mok, T. S., Wu, Y. L., Yu, C. J., et al. (2009). Randomized, placebo-controlled, phase II study of sequential erlotinib and chemotherapy as first-line treatment for advanced non-small cell lung cancer. Journal of Clinical Oncology, 27, 5080–5087.

    Article  PubMed  CAS  Google Scholar 

  18. Paez, J. G., Janne, P. A., Lee, J. C., et al. (2004). EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science, 304, 1497–1500.

    Article  PubMed  CAS  Google Scholar 

  19. Lynch, T. J., Bell, D. W., Sordella, R., et al. (2004). Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small cell lung cancer to gefitinib. New England Journal of Medicine, 350, 2129–2139.

    Article  PubMed  CAS  Google Scholar 

  20. Takano, T., Ohe, Y., Sakamoto, H., et al. (2005). Epidermal growth factor receptor gene mutations and increased copy numbers predict gefitinib sensitivity in patients with recurrent non-small-cell lung cancer. Journal of Clinical Oncology, 23, 6829–6837.

    Article  PubMed  CAS  Google Scholar 

  21. Shigematsu, H., Lin, L., Takahashi, T., et al. (2005). Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. Journal of the National Cancer Institute, 97, 339–346.

    Article  PubMed  CAS  Google Scholar 

  22. Yatabe, Y., Takahashi, T., & Mitsudomi, T. (2008). Epidermal growth factor receptor gene amplification is acquired in association with tumor progression of EGFR-mutated lung cancer. Cancer Research, 68, 2106–2111.

    Article  PubMed  CAS  Google Scholar 

  23. Matsumoto, S., Iwakawa, R., Kohno, T., et al. (2006). Frequent EGFR mutations in noninvasive bronchioloalveolar carcinoma. International Journal of Cancer, 118, 2498–2504.

    Article  CAS  Google Scholar 

  24. Tanaka, R., Wang, D., Morishita, Y., et al. (2005). Loss of function of p16 gene and prognosis of pulmonary adenocarcinoma. Cancer, 103, 608–615.

    Article  PubMed  CAS  Google Scholar 

  25. Nakanishi, H., Matsumoto, S., Iwakawa, R., et al. (2009). Whole genome comparison of allelic imbalance between noninvasive and invasive small-sized lung adenocarcinomas. Cancer Research, 69, 1615–1623.

    Article  PubMed  CAS  Google Scholar 

  26. Sato, K., Ueda, Y., Shikata, H., & Katsuda, S. (2006). Bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type: immunohistochemical studies and mutation analysis of the p53 gene. Pathology, Research and Practice, 202, 751–756.

    Article  PubMed  CAS  Google Scholar 

  27. Soda, M., Choi, Y. L., Enomoto, M., et al. (2007). Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature, 448, 561–566.

    Article  PubMed  CAS  Google Scholar 

  28. Inamura, K., Takeuchi, K., Togashi, Y., et al. (2008). EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers. Journal of Thoracic Oncology, 3, 13–17.

    Article  PubMed  Google Scholar 

  29. Tanaka, R., Ishiyama, T., Uchihara, T., et al. (2006). Expression of the Bax inhibitor-1 gene in pulmonary adenocarcinoma. Cancer, 106, 648–653.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan

    Masayuki Noguchi

Authors
  1. Masayuki Noguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Masayuki Noguchi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Noguchi, M. Stepwise progression of pulmonary adenocarcinoma—clinical and molecular implications. Cancer Metastasis Rev 29, 15–21 (2010). https://doi.org/10.1007/s10555-010-9210-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-010-9210-y

Keywords

Search

Navigation