This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Shin, D. M. Articles by Hittelman, W. N. Search for Related Content PubMed PubMed Citation Articles by Shin, D. M. Articles by Hittelman, W. N.

p53 Protein Accumulation and Genomic Instability in Head and Neck Multistep Tumorigenesis¹

Departments of Thoracic/Head and Neck Medical Oncology [D. M. S., S. M. L., W. K. H.], Pathology [J. Y. R.], Clinical Cancer Prevention [S. M. L.], Biostatistics [J. J. L.], and Clinical Investigations [N. C., W. N. H.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Head and neck cancer develops in a multistep process and is associated with increasing frequencies of p53 alterations and with increasing genomic instability. To study the relationship of p53 alterations and genomic instability during head and neck tumorigenesis, we analyzed p53 protein expression and chromosome 9 and 17 polysomy in 48 squamous cell carcinomas of the head and neck and their adjacent normal epithelium (31 sites), hyperplastic (24 sites), and dysplastic lesions (26 sites). Normal oral epithelium obtained from seven nonsmoking, cancer-free individuals served as negative controls. Six (19%) of 31 lesions in adjacent normal epithelium, 7 (29%) of 24 hyperplastic lesions, 12 (46%) of 26 dysplastic lesions, and 28 (58%) of 48 squamous cell carcinomas expressed p53. In contrast, no normal control epithelium had detectable p53 expression. To determine the relationship between dysregulated p53 expression and genomic instability during tumorigenesis, we compared p53 immunohistochemistry distributions and chromosome polysomy levels (by chromosome in situ hybridization) in different histological groups associated with tissue progression. Although the degree of chromosome polysomy increased for all of the groups during histological progression, lesions with dysregulated p53 expression showed nearly 2–4-fold increased levels of chromosome polysomy. This trend was significant for dysplastic lesions (P = 0.005 and P = 0.002 for chromosomes 9 and 17, respectively) and for squamous cell carcinoma (P = 0.005 and P = 0.002 for chromosomes 9 and 17, respectively). Image analysis studies for 28 p53-expressing tumors and their adjacent premalignant lesions demonstrated a strong spatial correlation between stepwise transitions from low to high p53 expression and increased chromosome polysomy frequencies in 13 (46%) of 28 cases. These findings suggest that altered p53 expression is associated with increased genetic instability in preneoplastic epithelium and may play a driving force for increasing the rate of accumulation of genetic events during head and neck tumorigenesis.

This article has been cited by other articles:

				T. K.S. Ku, D. C. Nguyen, M. Karaman, P. Gill, J. G. Hacia, and D. L. Crowe Loss of p53 Expression Correlates with Metastatic Phenotype and Transcriptional Profile in a New Mouse Model of Head and Neck Cancer Mol. Cancer Res., April 1, 2007; 5(4): 351 - 362. [Abstract] [Full Text] [PDF]

				S. M. Lippman, J. Sudbo, and W. K. Hong Oral Cancer Prevention and the Evolution of Molecular-Targeted Drug Development J. Clin. Oncol., January 10, 2005; 23(2): 346 - 356. [Abstract] [Full Text] [PDF]

				C. R. Herzog, T. R. Devereux, B. Pittman, and M. You Carcinogenic Induction Directs the Selection of Allelic Losses in Mouse Lung Tumorigenesis Cancer Res., November 15, 2002; 62(22): 6424 - 6429. [Abstract] [Full Text] [PDF]

				D.-S. Yoon, R. P. Wersto, W. Zhou, F. J. Chrest, E. S. Garrett, T. K. Kwon, and E. Gabrielson Variable Levels of Chromosomal Instability and Mitotic Spindle Checkpoint Defects in Breast Cancer Am. J. Pathol., August 1, 2002; 161(2): 391 - 397. [Abstract] [Full Text] [PDF]