Original Article

You have full text access to this OnlineOpen article

Loss of function of p16 gene and prognosis of pulmonary adenocarcinoma

  1. Ryota Tanaka M.D.1,2,
  2. Daye Wang Ph.D.2,
  3. Yukio Morishita M.D.2,
  4. Yukinori Inadome M.D.2,
  5. Yuko Minami M.D.2,
  6. Tatsuo Iijima M.D.2,
  7. Shimao Fukai M.D.3,
  8. Tomoyuki Goya M.D.1,
  9. Masayuki Noguchi M.D.2,†,*

Article first published online: 20 DEC 2004

DOI: 10.1002/cncr.20827

Issue

Cancer

Cancer

Volume 103, Issue 3, pages 608–615, 1 February 2005

Additional Information

How to Cite

Tanaka, R., Wang, D., Morishita, Y., Inadome, Y., Minami, Y., Iijima, T., Fukai, S., Goya, T. and Noguchi, M. (2005), Loss of function of p16 gene and prognosis of pulmonary adenocarcinoma. Cancer, 103: 608–615. doi: 10.1002/cncr.20827

Author Information

  1. 1

    Department of Surgery II, Institute of Medical Sciences, Kyorin University, Tokyo, Japan

  2. 2

    Department of Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan

  3. 3

    Department of Surgery, Ibarakihigashi National Hospital, Ibaraki, Japan

  1. †

    Fax: (011) 81-29-853-3150

*Department of Pathology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-shi, Ibaraki 305-8575, Japan

Publication History

  1. Issue published online: 20 JAN 2005
  2. Article first published online: 20 DEC 2004
  3. Manuscript Accepted: 18 OCT 2004
  4. Manuscript Revised: 3 OCT 2004
  5. Manuscript Received: 14 JUN 2004

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (345K)

Keywords:

  • nonsmall cell lung carcinoma;
  • pulmonary adenocarcinoma;
  • stepwise progression;
  • p16;
  • CpG island methylation;
  • loss of heterozygosity;
  • immunohistochemistry;
  • tumor suppressor gene;
  • prognostic factor;
  • carcinogenesis

Abstract

BACKGROUND

Stepwise progression of peripheral-type lung adenocarcinoma was characterized morphologically and was related to prognosis. Expression of the tumor suppressor gene p16 in pulmonary adenocarcinoma decreased, mainly as a result of aberrant methylation of the CpG islands of the promoter region.

METHODS

Aberrant methylation status of the p16 promoter region, the expression of its product, and loss of heterozygosity (LOH) on 9p21 were examined in surgically resected lung specimens from 57 patients (28 males and 29 females) with peripheral-type lung adenocarcinoma measuring ≤ 2 cm in diameter.

RESULTS

Aberrant methylation of the p16 promoter region, negative p16 protein expression, and LOH of the 9p21 region were detected in 40.4%, 50.9%, and 40.4% of tumor samples, respectively. The alterations of the p16 gene were associated with poor prognosis, and in particular the prognosis of patients with aberrant p16 methylation was significantly worse than that of patients without aberrant methylation. These alterations also were associated with morphologic classification into bronchioloalveolar carcinoma (BAC) and non-BAC adenocarcinoma. Both aberrant methylation and LOH of 9p21 were associated with negative protein expression, but the former was correlated more closely with loss of function than was the latter. Cases with both alterations were completely negative for expression of the p16 gene product.

CONCLUSIONS

Aberrant methylation of the promoter region of the p16 gene and loss of expression of its product were in accord with the multistep progression of peripheral-type lung adenocarcinoma, and these alterations were associated closely with poor prognosis of the disease. Cancer 2005. © 2004 American Cancer Society.

View Full Article (HTML) Get PDF (345K)