This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hayashi, H. Articles by Kitamura, H. Search for Related Content PubMed PubMed Citation Articles by Hayashi, H. Articles by Kitamura, H.

American Journal of Pathology, Vol 151, 461-470, Copyright © 1997 by American Society for Investigative Pathology

REGULAR ARTICLES

Analysis of p21Waf1/Cip1 expression in normal, premalignant, and malignant cells during the development of human lung adenocarcinoma

H Hayashi, H Miyamoto, T Ito, Y Kameda, N Nakamura, Y Kubota and H Kitamura
Department of Pathology, Yokohama City University School of Medicine, Japan.

Our studies suggested that adenocarcinoma of the peripheral lung mostly develops by several steps from atypical adenomatous hyperplasia through early adenocarcinoma to overt adenocarcinoma, and that some p53 abnormalities play an important role in this progression. In the present study, we examined by immunohistochemistry the expression of p53-inducible cyclin-dependent kinase inhibitor p21Waf1/Cip1 (p21) in the cells at various developmental stages of lung adenocarcinoma (32 lesions of adenomatous hyperplasia, 14 of early adenocarcinoma, 23 of well differentiated adenocarcinoma, and 17 of moderately or poorly differentiated adenocarcinoma) in comparison with 19 reactive proliferative lesions and analyzed the relationship between p53 and p21 expression. Bronchioalveolar cells in the normal lung expressed very little or no p21 and no p53 expression. In not only reactive but also neoplastic lesions regardless of their developmental stage, the cells expressed p21 at various frequencies. The average labeling indices ranged from 5.4 to 13.8%, and there was no significant difference between any of these categories. The expression of p21, however, tended to be relatively low in moderately and poorly differentiated adenocarcinomas (5.5%) compared to well differentiated adenocarcinomas (12.2%), and high-level p21 expressors (10% < or = positive cells) were more frequent in the latter group (1 of 17 (6%) versus 3 of 23 (35%), P < 0.05), suggesting that p21 expression is affected by the degree of differentiation of the neoplastic cells. Although the correlation was positive between the expression of p21 and p53 in reactive lesions (r = 0.88; P < 0.001), none was found in neoplastic lesions at any step or grade (-0.12 < or = r < or = 0.26). These results indicated that p21 expression depends upon p53 expression in reactive lung cells, whereas p21 expression is at least in part independent of that of p53 from the earliest to the most fully developed step of lung adenocarcinoma tumorigenesis. We concluded that disruption of the p53-dependent cell cycle regulation is a very early event in the tumorigenesis of lung adenocarcinoma.

This article has been cited by other articles:

				M. Lucattelli, S. Fineschi, P. Geppetti, N. P. Gerard, and G. Lungarella Neurokinin-1 Receptor Blockade and Murine Lung Tumorigenesis Am. J. Respir. Crit. Care Med., September 15, 2006; 174(6): 674 - 683. [Abstract] [Full Text] [PDF]

				K. Kameyama, C.-l. Huang, D. Liu, D. Masuya, T. Nakashima, S. Sumitomo, Y. Takami, M. Kinoshita, and H. Yokomise Reduced ING1b Gene Expression Plays an Important Role in Carcinogenesis of Non-Small Cell Lung Cancer Patients Clin. Cancer Res., October 15, 2003; 9(13): 4926 - 4934. [Abstract] [Full Text] [PDF]

				T. Shoji, F. Tanaka, T. Takata, K. Yanagihara, Y. Otake, N. Hanaoka, R. Miyahara, T. Nakagawa, Y. Kawano, S. Ishikawa, et al. Clinical Significance of p21 Expression in Non-Small-Cell Lung Cancer J. Clin. Oncol., September 15, 2002; 20(18): 3865 - 3871. [Abstract] [Full Text] [PDF]

				K M Kerr Pulmonary preinvasive neoplasia J. Clin. Pathol., April 1, 2001; 54(4): 257 - 271. [Abstract] [Full Text] [PDF]

				H. Kanazawa, M. Ebina, N. Ino-oka, M. Shimizukawa, T. Takahashi, S. Fujimura, T. Imai, and T. Nukiwa Transition from Squamous Cell Carcinoma to Adenocarcinoma in Adenosquamous Carcinoma of the Lung Am. J. Pathol., April 1, 2000; 156(4): 1289 - 1298. [Abstract] [Full Text] [PDF]

				K. Okudela, T. Ito, H. Mitsui, H. Hayashi, N. Udaka, M. Kanisawa, and H. Kitamura The Role of p53 in Bleomycin-Induced DNA Damage in the Lung : A Comparative Study with the Small Intestine Am. J. Pathol., October 1, 1999; 155(4): 1341 - 1351. [Abstract] [Full Text] [PDF]

				M. Baekelandt, R. Holm, C. G. Trope, J. M. Nesland, and G. B. Kristensen Lack of Independent Prognostic Significance of p21 and p27 Expression in Advanced Ovarian Cancer: An Immunohistochemical Study Clin. Cancer Res., October 1, 1999; 5(10): 2848 - 2853. [Abstract] [Full Text] [PDF]