| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Departments of Thoracic/Head and Neck Medical Oncology [D. M. S., W. K. H.], Pathology [J. Y. R.], and Clinical Investigation [W. N. H.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
The development of head and neck cancer, believed to result from field cancerization and a multistep process of tumorigenesis, is often associated with an accumulation of genotypic and phenotypic alterations. The phenotypic changes could be the result of dysregulation of growth control genes such as epidermal growth factor receptor (EGFR). With the goal of identifying a potential biomarker of the multistep process of tumorigenesis, we studied specimens of 36 head and neck squamous cell carcinomas from 5 different sites that contained normal epithelia and/or premalignant lesions adjacent to the tumors. Almost all of the individuals from whom these specimens were obtained had been exposed to first-hand smoking and/or alcohol consumption. Using a monoclonal anti-EGFR antibody for immunohistochemical analysis on paraffin-embedded sections with attached 886 cells for internal control, the levels of EGFR expression were assessed by image analysis. The relative staining intensity of EGFR in normal epithelia adjacent to tumors was 2-fold higher than that in normal control epithelium (P = 0.021), suggesting that, even in histologically normal epithelium, EGFR was already up-regulated in tissues surrounding tumors. These findings supported the theory of field cancerization in head and neck tumorigenesis. As tissue progressed from normal tissue adjacent to tumor to hyperplasia and to dysplasia, EGFR expression remained elevated. However, in the step from dysplasia to squamous cell carcinoma, EGFR expression was further and dramatically up-regulated (P = 0.01). Therefore, these results indicate that EGFR dysregulation happens in two steps, the moderate up-regulation of EGFR expression in normal epithelium adjacent to tumor and the further up-regulation of EGFR expression in the change from dysplasia to squamous cell carcinoma. In summary, the studies presented here indicate that EGFR dysregulation might be a useful marker for identifying individuals at risk of tumor development and an intermediate end point in chemoprevention trials.
1 Supported in part by NIH Grants CA-52501, CA-16672, CA-48364, and CA-45746. D. M. S. is a recipient of the Clinical Oncology Career Development Award (ACS-91-271) from the American Cancer Society.
2 To whom requests for reprints should be addressed, at Department of Thoracic/Head and Neck Medical Oncology, Box 80, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
Received 1/10/94. Accepted 5/ 2/94.
This article has been cited by other articles:
|
|
 |
|
  Role of Cyclooxygenase-2 in Tumor Progression and Survival of Head and Neck Squamous Cell Carcinoma Cancer Prevention Research, September 1, 2009; 2(9): 823 - 829.
|
|
|
|
|
|
A.R.M. R. Amin, F. R. Khuri, Z. Chen, and D. M. Shin Synergistic Growth Inhibition of Squamous Cell Carcinoma of the Head and Neck by Erlotinib and Epigallocatechin-3-Gallate: The Role of p53-Dependent Inhibition of Nuclear Factor-{kappa}B Cancer Prevention Research, June 1, 2009; 2(6): 538 - 545. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Choi and J.N. Myers Molecular Pathogenesis of Oral Squamous Cell Carcinoma: Implications for Therapy Journal of Dental Research, January 1, 2008; 87(1): 14 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Choong and E. Vokes Expanding Role of the Medical Oncologist in the Management of Head and Neck Cancer CA Cancer J Clin, January 1, 2008; 58(1): 32 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Agulnik, G. da Cunha Santos, D. Hedley, T. Nicklee, P. P. dos Reis, J. Ho, G. R. Pond, H. Chen, S. Chen, Y. Shyr, et al. Predictive and Pharmacodynamic Biomarker Studies in Tumor and Skin Tissue Samples of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck Treated With Erlotinib J. Clin. Oncol., June 1, 2007; 25(16): 2184 - 2190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kalyankrishna and J. R. Grandis Epidermal Growth Factor Receptor Biology in Head and Neck Cancer J. Clin. Oncol., June 10, 2006; 24(17): 2666 - 2672. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Lippman and J. J. Lee Reducing the "Risk" of Chemoprevention: Defining and Targeting High Risk--2005 AACR Cancer Research and Prevention Foundation Award Lecture. Cancer Res., March 15, 2006; 66(6): 2893 - 2903. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Choe, X. Zhang, H. J. C. Shin, D. M. Shin, and Z. Chen Interaction between epidermal growth factor receptor- and cyclooxygenase 2-mediated pathways and its implications for the chemoprevention of head and neck cancer Mol. Cancer Ther., September 1, 2005; 4(9): 1448 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, Z. Chen, M. S. Choe, Y. Lin, S.-Y. Sun, H. S. Wieand, H. J. C. Shin, A. Chen, F. R. Khuri, and D. M. Shin Tumor Growth Inhibition by Simultaneously Blocking Epidermal Growth Factor Receptor and Cyclooxygenase-2 in a Xenograft Model Clin. Cancer Res., September 1, 2005; 11(17): 6261 - 6269. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Dannenberg, S. M. Lippman, J. R. Mann, K. Subbaramaiah, and R. N. DuBois Cyclooxygenase-2 and Epidermal Growth Factor Receptor: Pharmacologic Targets for Chemoprevention J. Clin. Oncol., January 10, 2005; 23(2): 254 - 266. [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]
|
|
|
|
 |
|
 J. C. Rhee, F. R. Khuri, and D. M. Shin Advances in Chemoprevention of Head and Neck Cancer Oncologist, June 1, 2004; 9(3): 302 - 311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Grunwald and M. Hidalgo Developing Inhibitors of the Epidermal Growth Factor Receptor for Cancer Treatment J Natl Cancer Inst, June 18, 2003; 95(12): 851 - 867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. G. Izzo, V. A. Papadimitrakopoulou, D. D. Liu, P. L. C. den Hollander, I. M. Babenko, J. Keck, A. K. El-Naggar, D. M. Shin, J. J. Lee, W. K. Hong, et al. Cyclin D1 Genotype, Response to Biochemoprevention, and Progression Rate to Upper Aerodigestive Tract Cancer J Natl Cancer Inst, February 5, 2003; 95(3): 198 - 205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Gupta, W. G. McKenna, C. N. Weber, M. D. Feldman, J. D. Goldsmith, R. Mick, M. Machtay, D. I. Rosenthal, V. J. Bakanauskas, G. J. Cerniglia, et al. Local Recurrence in Head and Neck Cancer: Relationship to Radiation Resistance and Signal Transduction Clin. Cancer Res., March 1, 2002; 8(3): 885 - 892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. O'Shaughnessy, G. J. Kelloff, G. B. Gordon, A. J. Dannenberg, W. K. Hong, C. J. Fabian, C. C. Sigman, M. M. Bertagnolli, S. P. Stratton, S. Lam, et al. Treatment and Prevention of Intraepithelial Neoplasia: An Important Target for Accelerated New Agent Development : Recommendations of the American Association for Cancer Research Task Force on the Treatment and Prevention of Intraepithelial Neoplasia Clin. Cancer Res., February 1, 2002; 8(2): 314 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S. Soukos, M. R. Hamblin, S. Keel, R. L. Fabian, T. F. Deutsch, and T. Hasan Epidermal Growth Factor Receptor-targeted Immunophotodiagnosis and Photoimmunotherapy of Oral Precancer in Vivo Cancer Res., June 1, 2001; 61(11): 4490 - 4496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Shin, N. J. Donato, R. Perez-Soler, H. J. C. Shin, J. Y. Wu, P. Zhang, K. Lawhorn, F. R. Khuri, B. S. Glisson, J. Myers, et al. Epidermal Growth Factor Receptor-targeted Therapy with C225 and Cisplatin in Patients with Head and Neck Cancer Clin. Cancer Res., May 1, 2001; 7(5): 1204 - 1213. [Abstract] [Full Text]
|
|
|
|
|
|
H. Shiotani, A. Denda, K. Yamamoto, W. Kitayama, T. Endoh, Y. Sasaki, M. Tsutsumi, M. Sugimura, and Y. Konishi Increased Expression of Cyclooxygenase-2 Protein in 4-Nitroquinoline-1-oxide-induced Rat Tongue Carcinomas and Chemopreventive Efficacy of a Specific Inhibitor, Nimesulide Cancer Res., February 1, 2001; 61(4): 1451 - 1456. [Abstract] [Full Text]
|
|
|
|
|
|
H. J. Roh, D. M. Shin, J. S. Lee, J. Y. Ro, M. A. Tainsky, W. K. Hong, and W. N. Hittelman Visualization of the Timing of Gene Amplification during Multistep Head and Neck Tumorigenesis Cancer Res., November 1, 2000; 60(22): 6496 - 6502. [Abstract] [Full Text]
|
|
|
|
|
|
K. Tae, A. K. El-Naggar, E. Yoo, L. Feng, J. J. Lee, W. K. Hong, W. N. Hittelman, and D. M. Shin Expression of Vascular Endothelial Growth Factor and Microvessel Density in Head and Neck Tumorigenesis Clin. Cancer Res., July 1, 2000; 6(7): 2821 - 2828. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. G. C. T. van Oijen and P. J. Slootweg Oral Field Cancerization: Carcinogen-induced Independent Events or Micrometastatic Deposits? Cancer Epidemiol. Biomarkers Prev., March 1, 2000; 9(3): 249 - 256. [Abstract] [Full Text]
|
|
|
|
|
|
G. Chan, J. O. Boyle, E. K. Yang, F. Zhang, P. G. Sacks, J. P. Shah, D. Edelstein, R. A. Soslow, A. T. Koki, B. M. Woerner, et al. Cyclooxygenase-2 Expression Is Up-Regulated in Squamous Cell Carcinoma of the Head and Neck Cancer Res., March 1, 1999; 59(5): 991 - 994. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
