© 1998 by Oxford University Press
Journal Of The National Cancer Institute, Vol 90, 824-832, Copyright © 1998 by Oxford University Press
JR Grandis, MF Melhem, WE Gooding, R Day, VA Holst, MM Wagener, SD Drenning and DJ Tweardy
BACKGROUND: The most accurate predictor of disease recurrence in patients
treated for head and neck squamous cell carcinoma is, at present, the
extent of regional lymph node metastasis. Since elevated levels of
epidermal growth factor receptor (EGFR) and of its ligand, transforming
growth factor-alpha (TGF-alpha), have been detected in primary tumors of
patients with head and neck squamous cell carcinoma, we determined whether
tumor levels of these proteins were of prognostic importance. METHODS:
Monoclonal antibodies specific for EGFR and TGF- alpha were used for
immunohistochemical detection of each protein in tissue sections of primary
tumors from 91 patients who were treated by surgical resection. Levels of
immunoreactive EGFR and TGF-alpha were quantified by use of a computerized
image analysis system and were normalized to appropriate standards. The
logrank test and proportional hazards regression analysis were used to
calculate the probability that EGFR and TGF-alpha levels were associated
with disease-free survival (i.e., no recurrence of cancer) and
cause-specific survival (i.e., patients do not die of their disease). All P
values were two-sided. RESULTS: When tumor levels of EGFR or TGF-alpha were
analyzed as continuous variables, disease-free survival and cause-specific
survival were reduced among patients with higher levels of EGFR (both P =
.0001) or TGF-alpha (both P = .0001). In a multivariate analysis, tumor
site, tumor level of EGFR, and tumor level of TGF-alpha were statistically
significant predictors of disease-free survival; in a similar analysis,
regional lymph node stage and tumor levels of EGFR and of TGF-alpha were
significant predictors of cause-specific survival. CONCLUSION: Quantitation
of EGFR and TGF-alpha protein levels in primary head and neck squamous cell
carcinomas may be useful in identifying subgroups of patients at high risk
of tumor recurrence and in guiding therapy.
ARTICLES
Levels of TGF-alpha and EGFR protein in head and neck squamous cell carcinoma and patient survival
Department of Otolaryngology, University of Pittsburgh School of Medicine, and University of Pittsburgh Cancer Institute, PA, USA. jgrandis@vms.cis.pitt.edu
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A. Hirata, F. Hosoi, M. Miyagawa, S.-i. Ueda, S. Naito, T. Fujii, M. Kuwano, and M. Ono HER2 Overexpression Increases Sensitivity to Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, through Inhibition of HER2/HER3 Heterodimer Formation in Lung Cancer Cells Cancer Res., May 15, 2005; 65(10): 4253 - 4260. [Abstract] [Full Text] [PDF]
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P. Chinnaiyan, S. Huang, G. Vallabhaneni, E. Armstrong, S. Varambally, S. A. Tomlins, A. M. Chinnaiyan, and P. M. Harari Mechanisms of Enhanced Radiation Response following Epidermal Growth Factor Receptor Signaling Inhibition by Erlotinib (Tarceva) Cancer Res., April 15, 2005; 65(8): 3328 - 3335. [Abstract] [Full Text] [PDF]
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L. H. Kalish, R. A. Kwong, I. E. Cole, R. M. Gallagher, R. L. Sutherland, and E. A. Musgrove Deregulated Cyclin D1 Expression Is Associated with Decreased Efficacy of the Selective Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Gefitinib in Head and Neck Squamous Cell Carcinoma Cell Lines Clin. Cancer Res., November 15, 2004; 10(22): 7764 - 7774. [Abstract] [Full Text] [PDF]
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S. M. Thomas, Q. Zeng, M. W. Epperly, W. E. Gooding, I. Pastan, Q. C. Wang, J. Greenberger, and J. R. Grandis Abrogation of Head and Neck Squamous Cell Carcinoma Growth by Epidermal Growth Factor Receptor Ligand Fused to Pseudomonas Exotoxin Transforming Growth Factor {alpha}-PE38 Clin. Cancer Res., October 15, 2004; 10(20): 7079 - 7087. [Abstract] [Full Text] [PDF]
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 N. R. Schechter, R. E. Wendt III, D. J. Yang, A. Azhdarinia, W. D. Erwin, A. M. Stachowiak, L. D. Broemeling, E. E. Kim, J. D. Cox, D. A. Podoloff, et al. Radiation Dosimetry of 99mTc-Labeled C225 in Patients with Squamous Cell Carcinoma of the Head and Neck J. Nucl. Med., October 1, 2004; 45(10): 1683 - 1687. [Abstract] [Full Text] [PDF]
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Q. Zhang, S. M. Thomas, S. Xi, T. E. Smithgall, J. M. Siegfried, J. Kamens, W. E. Gooding, and J. R. Grandis Src Family Kinases Mediate Epidermal Growth Factor Receptor Ligand Cleavage, Proliferation, and Invasion of Head and Neck Cancer Cells Cancer Res., September 1, 2004; 64(17): 6166 - 6173. [Abstract] [Full Text] [PDF]
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Z. Chen, X. Zhang, M. Li, Z. Wang, H. S. Wieand, J. R. Grandis, and D. M. Shin Simultaneously Targeting Epidermal Growth Factor Receptor Tyrosine Kinase and Cyclooxygenase-2, an Efficient Approach to Inhibition of Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., September 1, 2004; 10(17): 5930 - 5939. [Abstract] [Full Text] [PDF]
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C. Caulin, T. Nguyen, M. A. Longley, Z. Zhou, X.-J. Wang, and D. R. Roop Inducible Activation of Oncogenic K-ras Results in Tumor Formation in the Oral Cavity Cancer Res., August 1, 2004; 64(15): 5054 - 5058. [Abstract] [Full Text] [PDF]
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 K. E. Strunk, V. Amann, and D. W. Threadgill Phenotypic Variation Resulting From a Deficiency of Epidermal Growth Factor Receptor in Mice Is Caused by Extensive Genetic Heterogeneity That Can Be Genetically and Molecularly Partitioned Genetics, August 1, 2004; 167(4): 1821 - 1832. [Abstract] [Full Text] [PDF]
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E. E.W. Cohen, M. W. Lingen, and E. E. Vokes The Expanding Role of Systemic Therapy in Head and Neck Cancer J. Clin. Oncol., May 1, 2004; 22(9): 1743 - 1752. [Abstract] [Full Text] [PDF]
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H.-S. Lin, G. J. Berry, W. E. Fee Jr, D. J. Terris, and Z. Sun Identification of Tyrosine Kinases Overexpressed in Head and Neck Cancer Arch Otolaryngol Head Neck Surg, March 1, 2004; 130(3): 311 - 316. [Abstract] [Full Text] [PDF]
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M. Sumitomo, T. Asano, J. Asakuma, T. Asano, A. Horiguchi, and M. Hayakawa ZD1839 Modulates Paclitaxel Response in Renal Cancer by Blocking Paclitaxel-Induced Activation of the Epidermal Growth Factor Receptor-Extracellular Signal-Regulated Kinase Pathway Clin. Cancer Res., January 15, 2004; 10(2): 794 - 801. [Abstract] [Full Text] [PDF]
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D. Soulieres, N. N. Senzer, E. E. Vokes, M. Hidalgo, S. S. Agarwala, and L. L. Siu Multicenter Phase II Study of Erlotinib, an Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck J. Clin. Oncol., January 1, 2004; 22(1): 77 - 85. [Abstract] [Full Text] [PDF]
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 J-L Yang, X-J Qu, P J Russell, and D Goldstein Regulation of epidermal growth factor receptor in human colon cancer cell lines by interferon {alpha} Gut, January 1, 2004; 53(1): 123 - 129. [Abstract] [Full Text] [PDF]
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R. S. Herbst and P. A. Bunn Jr. Targeting the Epidermal Growth Factor Receptor in Non-Small Cell Lung Cancer Clin. Cancer Res., December 1, 2003; 9(16): 5813 - 5824. [Abstract] [Full Text] [PDF]
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T. M. Grana, C. I. Sartor, and A. D. Cox Epidermal Growth Factor Receptor Autocrine Signaling in RIE-1 Cells Transformed by the Ras Oncogene Enhances Radiation Resistance Cancer Res., November 15, 2003; 63(22): 7807 - 7814. [Abstract] [Full Text] [PDF]
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S. Xi, Q. Zhang, W. E. Gooding, T. E. Smithgall, and J. R. Grandis Constitutive Activation of Stat5b Contributes to Carcinogenesis in Vivo Cancer Res., October 15, 2003; 63(20): 6763 - 6771. [Abstract] [Full Text] [PDF]
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H. Niwa, A. L. Wentzel, M. Li, W. E. Gooding, V. W. Y. Lui, and J. R. Grandis Antitumor Effects of Epidermal Growth Factor Receptor Antisense Oligonucleotides in Combination with Docetaxel in Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., October 15, 2003; 9(13): 5028 - 5035. [Abstract] [Full Text] [PDF]
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Q.-T. Le and A. J. Giaccia Therapeutic Exploitation of the Physiological and Molecular Genetic Alterations in Head and Neck Cancer Clin. Cancer Res., October 1, 2003; 9(12): 4287 - 4295. [Abstract] [Full Text] [PDF]
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D. M. Weinreich, D. M. Elaraj, M. Puhlmann, S. M. Hewitt, N. M. Carroll, E. D. Feldman, E. M. Turner, P. J. Spiess, and H. R. Alexander Effect of Interleukin 1 Receptor Antagonist Gene Transduction on Human Melanoma Xenografts in Nude Mice Cancer Res., September 15, 2003; 63(18): 5957 - 5961. [Abstract] [Full Text] [PDF]
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S. M. Thomas, F. M. Coppelli, A. Wells, W. E. Gooding, J. Song, J. Kassis, S. D. Drenning, and J. R. Grandis Epidermal Growth Factor Receptor-stimulated Activation of Phospholipase C{gamma}-1 Promotes Invasion of Head and Neck Squamous Cell Carcinoma Cancer Res., September 1, 2003; 63(17): 5629 - 5635. [Abstract] [Full Text] [PDF]
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J. Mendelsohn and J. Baselga Status of Epidermal Growth Factor Receptor Antagonists in the Biology and Treatment of Cancer J. Clin. Oncol., July 15, 2003; 21(14): 2787 - 2799. [Abstract] [Full Text] [PDF]
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C. L. Arteaga and J. Baselga Clinical Trial Design and End Points for Epidermal Growth Factor Receptor-targeted Therapies: Implications for Drug Development and Practice Clin. Cancer Res., May 1, 2003; 9(5): 1579 - 1589. [Full Text] [PDF]
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G. Gonzalez, T. Crombet, F. Torres, M. Catala, L. Alfonso, M. Osorio, E. Neninger, B. Garcia, A. Mulet, R. Perez, et al. Epidermal growth factor-based cancer vaccine for non-small-cell lung cancer therapy Ann. Onc., March 1, 2003; 14(3): 461 - 466. [Abstract] [Full Text] [PDF]
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 J. Brown, J. O'Prey, and P.R. Harrison Enhanced sensitivity of human oral tumours to the flavonol, morin, during cancer progression: involvement of the Akt and stress kinase pathways Carcinogenesis, February 1, 2003; 24(2): 171 - 177. [Abstract] [Full Text] [PDF]
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Q.-T. Le, P. D. Sutphin, S. Raychaudhuri, S. C. T. Yu, D. J. Terris, H. S. Lin, B. Lum, H. A Pinto, A. C. Koong, and A. J. Giaccia Identification of Osteopontin as a Prognostic Plasma Marker for Head and Neck Squamous Cell Carcinomas Clin. Cancer Res., January 1, 2003; 9(1): 59 - 67. [Abstract] [Full Text] [PDF]
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K. K. Ang, B. A. Berkey, X. Tu, H.-Z. Zhang, R. Katz, E. H. Hammond, K. K. Fu, and L. Milas Impact of Epidermal Growth Factor Receptor Expression on Survival and Pattern of Relapse in Patients with Advanced Head and Neck Carcinoma Cancer Res., December 15, 2002; 62(24): 7350 - 7356. [Abstract] [Full Text] [PDF]
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P. A. Janne, M. L. Taffaro, R. Salgia, and B. E. Johnson Inhibition of Epidermal Growth Factor Receptor Signaling in Malignant Pleural Mesothelioma Cancer Res., September 15, 2002; 62(18): 5242 - 5247. [Abstract] [Full Text] [PDF]
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R. S. Herbst, A.-M. Maddox, M. L. Rothenberg, E. J. Small, E. H. Rubin, J. Baselga, F. Rojo, W. K. Hong, H. Swaisland, S. D. Averbuch, et al. Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor ZD1839 Is Generally Well-Tolerated and Has Activity in Non-Small-Cell Lung Cancer and Other Solid Tumors: Results of a Phase I Trial J. Clin. Oncol., September 15, 2002; 20(18): 3815 - 3825. [Abstract] [Full Text] [PDF]
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F. McGregor, A. Muntoni, J. Fleming, J. Brown, D. H. Felix, D. G. MacDonald, E. K. Parkinson, and P. R. Harrison Molecular Changes Associated with Oral Dysplasia Progression and Acquisition of Immortality: Potential for Its Reversal by 5-Azacytidine Cancer Res., August 15, 2002; 62(16): 4757 - 4766. [Abstract] [Full Text] [PDF]
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 T. Kijima, H. Niwa, R. A. Steinman, S. D. Drenning, W. E. Gooding, A. L. Wentzel, S. Xi, and J. R. Grandis STAT3 Activation Abrogates Growth Factor Dependence and Contributes to Head and Neck Squamous Cell Carcinoma Tumor Growth in Vivo Cell Growth Differ., August 1, 2002; 13(8): 355 - 362. [Abstract] [Full Text] [PDF]
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J. N. Myers, F. C. Holsinger, B. N. Bekele, E. Li, S. A. Jasser, J. J. Killion, and I. J. Fidler Targeted Molecular Therapy for Oral Cancer With Epidermal Growth Factor Receptor Blockade: A Preliminary Report Arch Otolaryngol Head Neck Surg, August 1, 2002; 128(8): 875 - 879. [Abstract] [Full Text] [PDF]
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S.-M. Huang, J. Li, and P. M. Harari Molecular Inhibition of Angiogenesis and Metastatic Potential in Human Squamous Cell Carcinomas after Epidermal Growth Factor Receptor Blockade Mol. Cancer Ther., May 1, 2002; 1(7): 507 - 514. [Abstract] [Full Text] [PDF]
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C. J. Piyathilake, A. R. Frost, U. Manne, H. Weiss, W. C. Bell, D. C. Heimburger, and W. E. Grizzle Differential Expression of Growth Factors in Squamous Cell Carcinoma and Precancerous Lesions of the Lung Clin. Cancer Res., March 1, 2002; 8(3): 734 - 744. [Abstract] [Full Text] [PDF]
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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]
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A. Forastiere, W. Koch, A. Trotti, and D. Sidransky Head and Neck Cancer N. Engl. J. Med., December 27, 2001; 345(26): 1890 - 1900. [Full Text] [PDF]
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M. Masuda, M. Suzui, and I. B. Weinstein Effects of Epigallocatechin-3-gallate on Growth, Epidermal Growth Factor Receptor Signaling Pathways, Gene Expression, and Chemosensitivity in Human Head and Neck Squamous Cell Carcinoma Cell Lines Clin. Cancer Res., December 1, 2001; 7(12): 4220 - 4229. [Abstract] [Full Text] [PDF]
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