Clinical Cancer Research The Future of Cancer Research: Science and Patient Impact Infection and Cancer: Biology, Therapeutics, and Prevention
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
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, J. W.
Right arrow Articles by Lee, S. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, J. W.
Right arrow Articles by Lee, S. H.
Clinical Cancer Research Vol. 11, 2879-2882, April 15, 2005
© 2005 American Association for Cancer Research

Human Cancer Biology

Somatic Mutations of EGFR Gene in Squamous Cell Carcinoma of the Head and Neck

Jong Woo Lee1, Young Hwa Soung1, Su Young Kim1, Hyo Kyung Nam1, Won Sang Park1, Suk Woo Nam1, Min Sik Kim2, Dong Il Sun2, Youn Soo Lee3, Ja June Jang4, Jung Young Lee1, Nam Jin Yoo1 and Sug Hyung Lee1

Authors' Affiliations: Departments of 1 Pathology, 2 Otolaryngology and 3 Clinical Pathology, College of Medicine, Catholic University of Korea; and 4 Department of Pathology, Seoul National University College of Medicine, Seoul, Korea

Requests for reprints: Sug Hyung Lee, Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea. Phone: 82-2-590-1188; Fax: 82-2-537-6586; E-mail: suhulee{at}catholic.ac.kr.


   Abstract
Top
 Abstract
Materials and Methods
 Results
 Discussion
 References
 
Purpose: Recently, the kinase domain mutations of epidermal growth factor receptor (EGFR) gene have been identified in non–small-cell lung cancer, and these mutations have been related to the clinical response to the tyrosine kinase inhibitor gefitinib. Gefitinib treatment has also shown clinical benefits in squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to explore the possibility that SCCHN harbored the EGFR mutations.

Experimental Design: In this study, we analyzed EGFR gene in 41 SCCHN for the detection of the somatic mutations by PCR-single-strand conformational polymorphism analysis.

Results: Overall, we detected three EGFR mutations (7.3%), and all of the mutations were the same in-frame deletion mutation in exon 19 (E746_A750del).

Conclusion: These data indicated that in addition to non–small-cell lung cancer, SCCHN harbors the EGFR gene mutations, and suggested the rationale for the clinical applicability of gefinitib to SCCHN patients.

Key Words: EGFR • mutation • head and neck cancer • gefitinib • Iressa • oncogene

The epidermal growth factor receptor (EGFR), a receptor protein tyrosine kinase, regulates a number of cellular functions, including proliferation and survival, that are also crucial in tumorigenesis, thus making EGFR a promising target for the cancer therapies (1). Gefitinib (Iressa), which disrupts EGFR kinase activity by binding the ATP pocket within the kinase domain, is an orally active EGFR tyrosine kinase inhibitor (2). Gefitinib has been shown to reduce cellular proliferation in many tumor cell lines and tumor xenografts (3, 4). In the clinical trials, the clinical benefits of gefitinib have been identified mainly in non–small-cell lung cancer (NSCLC) patients (5, 6). However, because not all NSCLC patients exhibit the same response, there is considerable interest in prognostic indicators that might predict the response to gefitinib (5, 6). Recent studies showed that the kinase domain mutations of EGFR gene in the NSCLC tissues could predict significant clinical responses to gefitinib (7–9). All of the EGFR mutations affect amino acids near the ATP-binding pocket that is targeted by gefitinib. In addition to NSCLC, there is evidence that gefitinib could be a potential agent for the treatment of other tumors, including squamous cell carcinoma of the head and neck (SCCHN; ref. 10). In the preclinical studies, antitumor activity was observed in the SCCHN cells (11). In a phase II study, Cohen et al. reported that 11% of the SCCHN patients with gefitinib monotherapy had an objective tumor response (10). This study suggested the possibility that like NSCLC, the SCCHN harbors the EGFR mutations which might be responsible for the clinical response of gefitinib in the SCCHN patients. To explore this possibility, we have analyzed 41 SCCHN tissues and found that EGFR gene is somatically mutated in the human SCCHN.


   Materials and Methods
Top
 Abstract
 Materials and Methods
Results
 Discussion
 References
 
Tissue samples and microdissection. Twelve cases of methacarn-fixed and 29 cases of formalin-fixed SCCHN were randomly selected for the study. The tumors consisted of 34 larynx, five tongue, and two tonsil SCCHN. All of the tissues were reviewed independently by two pathologists. We analyzed the primary lesions in 18 cases, and both primary and nodal metastatic lesions in 23 cases. All of the patients were Korean. The male to female ratio was 37:4. Ages of the patients ranged from 43 to 79 years with an average of 59.8 years. The patients consisted of 27 current smokers, 8 former smokers, and 6 nonsmokers (Table 1).


View this table:
[in this window]
[in a new window]
  		Table 1. Demographic data and EGFR mutations of the SCCHN

 
Malignant cells and normal cells were selectively procured from H&E-stained slides using a 301/2 gauge hypodermic needle (Becton Dickinson, Franklin Lakes, NJ) affixed to a micromanipulator, as described previously (12). DNA extraction was done by a modified single-step DNA extraction method, as previously described (12).

PCR-single-strand conformational polymorphism analysis. All of the EGFR mutations in the NSCLC have been reported within exons 18, 19, and 21 (7–9). Thus, we analyzed the EGFR mutation in these three exons. Genomic DNAs from tumor cells and normal cells from the same patients were amplified with three primer pairs covering exons 18, 19, and 21 of human EGFR gene. Numbering of cDNA of EGFR was done with respect to the ATG start codon. Radioisotope ([32P]dCTP) was incorporated into the PCR products for detection by autoradiogram. The procedures of PCR and single-strand conformational polymorphism (SSCP) analysis were done as described previously (13). After SSCP, bands showing mobility shifts were cut out from the dried gel and reamplified for 30 cycles using the same primer sets. Sequencing of the PCR products was carried out using the cyclic sequencing kit (Perkin-Elmer, Foster City, CA). We repeated the experiments twice, including PCR, SSCP, and sequencing analysis to ensure the specificity of the results.


   Results
Top
 Abstract
 Materials and Methods
 Results
Discussion
 References
 
Genomic DNAs of the SCCHN isolated through the microdissection were analyzed for the detection of mutations in exons 18, 19, and 21 of EGFR gene by PCR-SSCP analysis. Enrichment and DNA sequencing analysis of aberrantly migrating bands on the SSCP led to the identification of 3 EGFR mutations (cases 11, 20, and 33) of the 41 SCCHN (7.3%; Fig. 1 and Table 1). The mutations were detected in exon 19, but not in exons 18 and 21. Also, all of the mutations were the same type mutation (2236_2250delGAATTAAGAGAAGCA) which would result in a five-amino-acid deletion (E746_A750del). None of the normal samples from the same patients showed evidence of mutations by SSCP (Fig. 1A), indicating the mutations had increased somatically. We repeated the experiments twice, including PCR, SSCP and sequencing analysis, to ensure the specificity of the results, and found that the data were consistent (data not shown). As a positive control for the SSCP of exon 21, we included a lung adenocarcinoma tissue with the known hotspot EGFR mutation in exon 21 (L858R) by the same method (Fig. 1B). Also, to confirm the SSCP data on exon 18, we analyzed the PCR products by direct sequencing and found that there was no EGFR mutation in exon 18 (data not shown).



View larger version (50K):
[in this window]
[in a new window]
  		Fig. 1. Mutations of EGFR gene in the SCCHN. SSCP (A and B) and sequencing analysis (C) of the EGFR from tumors (lane T) and normal tissues (lane N). A, the SSCP (exon 19) of the tumors of cases 11, 33, and 20 shows aberrant bands as compared with SSCP from normal tissue (N). SSCP of the DNA from tumor of the case 20 shows only aberrant bands without any wild-type bands. Aberrant bands not indicated by the arrows were sequenced and proven to be heteroduplex bands. B, the SSCP (exon 21) of the SCCHNs showed no aberrant bands (arrows) compared with the SSCP of a lung adenocarcinoma with the L858R mutation [(+) control]. C, sequencing analysis from the aberrant band indicated by the arrows from the case 20 in the SSCP (A) shows a 15-bp deletion.

 
Whereas the SSCP patterns of cases 11 and 33 at the mutation sites showed both wild-type and aberrant bands, the SSCP pattern of the case 20 showed only aberrant bands of mutant allele without those of the wild-type allele (Fig. 1), and direct sequencing analysis also revealed only mutant sequence without wild-type one, indicating either homozygous mutations or hemizygous mutation with allelic loss.

All of the three EGFR mutations were identified in both primary and metastatic lesions. Also, all of the three mutations were detected in laryngeal squamous cell carcinomas, but the correlation was not statistically significant (Fisher's exact test, P > 0.05). All of the patients with the mutation were current smokers, but the association of smoking status and the EGFR mutation was not significant (Fisher's exact test, P > 0.05).


   Discussion
Top
 Abstract
 Materials and Methods
 Results
 Discussion
References
 
Because gefitinib had an anticancer activity in the SCCHN and the EGFR kinase domain mutation is known to mediate the gefitinib sensitivity, we expected that human SCCHN tissues would carry the EGFR mutations. In this study, we found that 7.3% of the SCCHN harbored EGFR mutations in the DNA sequences encoding the kinase domain. These data could account for the responses seen in the phase II trials of gefitinib, in which 11% of the SCCHN patients had an overall tumor response (10). It is known that somatic mutations in the tyrosine kinase domain of EGFR are more common in adenocarcinomas and never smokers in NSCLC. However, the data in this study showed that in the head and neck cancers the EGFR mutation occurred in squamous cell carcinomas and smokers. These observations suggest that the etiology of EGFR mutations in SSCHN might be different from that of lung cancer.

In addition to NSCLC, Lynch et al. (7) sought to find EGFR mutations in exons 19 and 21 in a panel of 108 cancer-derived cell lines from various origins, including seven head and neck cancer cell lines, but no EGFR mutations were detected. Explanations for the discrepancy between the presence of EGFR mutations in the SCCHN tissues in this study and the absence of the mutations in the SCCHN cell lines include: (a) the SCCHN cell lines might not be representative for the original tumor tissues; (b) the number of cell lines analyzed was too small to detect the EGFR mutations; and (c) there might be an ethnic difference in the distribution of the EGFR mutation in SSCHN as in the case of EGFR mutations of lung cancers. In regards to the second point, there is no statistical difference in the EGFR mutation frequency between the cell line study (0 of 7 samples) and our study (3 of 41 samples; Fisher's exact test, P > 0.05).

In the present study, all of the EGFR mutations in exon 19 were the E746_A750del. This is similar to the data of NSCLC, where the most common mutation in exon 19 has been the E746_A750del mutation among the 10 types of EGFR mutations reported (7–9). These data could raise the possibility that the contribution of EGFR mutations in the development of SCCHN might be similar to that of NSCLC. A central aim of cancer research has been to identify the mutated genes that are causally implicated in tumorigenesis. Mutations in cancer could be categorized either as functional alterations affecting key genes underlying the neoplastic process or nonfunctional "passenger" changes. The E746_A750del mutation seems to be a gain-of-function mutation that activates antiapoptosis pathways (14). Activation of the EGFR function and the relatively common incidence (7.3%) suggested that the EGFR mutations detected in this study may be functional alterations, but not passenger alterations in the SCCHN tumorigenesis.

The detection of only one type of EGFR mutations in exon 19 could raise the possibility that the PCR-SSCP method we used could not detect other types of mutations in these exons besides E746_A750del. However, this possibility is unlikely because we could detect nine types of EGFR deletion mutations in exon 19 from the genomic DNA of 80 lung adenocarcinoma and bronchioloalveolar cancer tissues by the same PCR-SSCP method.5

Mutant alleles of proto-oncogenes are considered dominant if they transform cells despite the presence of their normal alleles. EGFR gene, a proto-oncogene, has usually been mutated heterozygously in NSCLCs. However, Paez et al. and Pao et al. reported one and two nonheterozygous EGFR mutation(s) in exon 19 in NSCLC, respectively. In the current study, we also detected one nonheterozygous E746_A750del mutation in a SCCHN (case 20; Fig. 1). However, the functional difference between monoallelic and biallelic alterations of the EGFR gene in the tumorigenesis remains unknown at this stage.

Currently the EGFR kinase domain mutation seems to be the best predictor of sensitivity to gefitinib (15). However, it remains unknown as to whether the EGFR kinase domain mutation could be a predictor for the gefitinib therapy in SCCHN, too, although we found somatic mutations of the EGFR kinase domain mutation in the SCCHN. Clearly, therefore, studies are now needed that attempt to find the correlation between the EGFR kinase domain mutation and the gefitinib sensitivity in SCCHN.


   Footnotes
 
Grant support: Korea Science and Engineering Foundation (KOSEF) through the Cell Death Disease Research Center at The Catholic University of Korea (R13-2002-005-01004-0).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

5 Unpublished data. Back

Received 10/ 3/04; revised 1/ 4/05; accepted 1/24/05.


   References
Top
 Abstract
 Materials and Methods
 Results
 Discussion
 References
 

  1. Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 2003;284:31–53.[CrossRef][Medline]
  2. Wakeling AE, Guy SP, Woodburn JR, et al. ZD1839 (Iressa): an orally active inhibitor of epidermal growth factor signaling with potential for cancer therapy. Cancer Res 2002;62:5749–54.[Abstract/Free Full Text]
  3. Ciardiello F, Caputo R, Bianco R, et al. Antitumor effect and potentiation of cytotoxic drugs activity in human cancer cells by ZD-1839 (Iressa), an epidermal growth factor receptor-selective tyrosine kinase inhibitor. Clin Cancer Res 2000;6:2053–63.[Abstract/Free Full Text]
  4. Williams KJ, Telfer BA, Stratford IJ, Wedge SR. ZD1839 ('Iressa'), a specific oral epidermal growth factor receptor-tyrosine kinase inhibitor, potentiates radiotherapy in a human colorectal cancer xenograft model. Br J Cancer 2002;86:1157–61.[CrossRef][Medline]
  5. Fukuoka M, Yano S, Giaccone G, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer. J Clin Oncol 2003;21:2237–46.[Abstract/Free Full Text]
  6. Kris MG, Natale RB, Herbst RS, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003;290:2149–58.[Abstract/Free Full Text]
  7. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129–39.[Abstract/Free Full Text]
  8. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 2004;304:1497–500.[Abstract/Free Full Text]
  9. Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from "never smokers" and are associated with sensitivity of tumors to gefitinib and erlotinib. Proc Natl Acad Sci U S A 2004;101:13306–11.[Abstract/Free Full Text]
  10. Cohen EEW, Rosen F, Dekker A, et al. Phase II study of ZD1839 (Iressa) in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Proc Am Soc Clin Oncol 2002;21:225a (A899).
  11. Magne N, Fischel JL, Dubreuil A, et al. Influence of epidermal growth factor receptor (EGFR), p53 and intrinsic MAP kinase pathway status of tumour cells on the antiproliferative effect of ZD1839 ("Iressa"). Br J Cancer 2002;86:1518–23.[CrossRef][Medline]
  12. Lee JY, Dong SM, Kim SY, Yoo NJ, Lee SH, Park WS. A simple, precise and economical microdissection technique for analysis of genomic DNA from archival tissue sections. Virchows Arch 1998;433:305–9.[CrossRef][Medline]
  13. Kim HS, Lee JW, Soung YH, et al. Inactivating mutations of caspase-8 gene in colorectal carcinomas. Gastroenterology 2003;125:708–15.[CrossRef][Medline]
  14. Sordella R, Bell DW, Harber DA, Settleman J. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science 2004;305:1163–7.[Abstract/Free Full Text]
  15. Pao W, Miller VA, Venkatraman E, Kris MG. Predicting sensitivity of non-small-cell lung cancer to gefitinib: is there a role for P-Akt? J Natl Cancer Inst 2004;96:1117–9.[Free Full Text]



This article has been cited by other articles:


Home page
 Br. J. Radiol.Home page
C M West, L Joseph, and S Bhana
Epidermal growth factor receptor-targeted therapy
Br. J. Radiol., October 1, 2008; 81(Special_Issue_1): S36 - S44.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Thomas, P. Rochaix, A. Benlyazid, J. Sarini, M. Rives, J. L. Lefebvre, B. C. Allal, F. Courbon, E. Chatelut, and J.-P. Delord
Pilot Study of Neoadjuvant Treatment with Erlotinib in Nonmetastatic Head and Neck Squamous Cell Carcinoma
Clin. Cancer Res., December 1, 2007; 13(23): 7086 - 7092.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. Elser, L. L. Siu, E. Winquist, M. Agulnik, G. R. Pond, S. F. Chin, P. Francis, R. Cheiken, J. Elting, A. McNabola, et al.
Phase II Trial of Sorafenib in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Nasopharyngeal Carcinoma
J. Clin. Oncol., August 20, 2007; 25(24): 3766 - 3773.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
S. Temam, H. Kawaguchi, A. K. El-Naggar, J. Jelinek, H. Tang, D. D. Liu, W. Lang, J.-P. Issa, J. J. Lee, and L. Mao
Epidermal Growth Factor Receptor Copy Number Alterations Correlate With Poor Clinical Outcome in Patients With Head and Neck Squamous Cancer
J. Clin. Oncol., June 1, 2007; 25(16): 2164 - 2170.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. V. Sequist, D. W. Bell, T. J. Lynch, and D. A. Haber
Molecular Predictors of Response to Epidermal Growth Factor Receptor Antagonists in Non-Small-Cell Lung Cancer
J. Clin. Oncol., February 10, 2007; 25(5): 587 - 595.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
G. J. Riely, K. A. Politi, V. A. Miller, and W. Pao
Update on Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer
Clin. Cancer Res., December 15, 2006; 12(24): 7232 - 7241.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Perrone, S. Suardi, E. Pastore, P. Casieri, M. Orsenigo, S. Caramuta, G. Dagrada, M. Losa, L. Licitra, P. Bossi, et al.
Molecular and Cytogenetic Subgroups of Oropharyngeal Squamous Cell Carcinoma.
Clin. Cancer Res., November 15, 2006; 12(22): 6643 - 6651.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
C. H. Chung, K. Ely, L. McGavran, M. Varella-Garcia, J. Parker, N. Parker, C. Jarrett, J. Carter, B. A. Murphy, J. Netterville, et al.
Increased Epidermal Growth Factor Receptor Gene Copy Number Is Associated With Poor Prognosis in Head and Neck Squamous Cell Carcinomas
J. Clin. Oncol., September 1, 2006; 24(25): 4170 - 4176.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. C. Sok, F. M. Coppelli, S. M. Thomas, M. N. Lango, S. Xi, J. L. Hunt, M. L. Freilino, M. W. Graner, C. J. Wikstrand, D. D. Bigner, et al.
Mutant Epidermal Growth Factor Receptor (EGFRvIII) Contributes to Head and Neck Cancer Growth and Resistance to EGFR Targeting
Clin. Cancer Res., September 1, 2006; 12(17): 5064 - 5073.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. N. Blehm, P. E. Spiess, J. E. Bondaruk, M. E. Dujka, G. J. Villares, Y.-j. Zhao, O. Bogler, K. D. Aldape, H. B. Grossman, L. Adam, et al.
Mutations Within the Kinase Domain and Truncations of the Epidermal Growth Factor Receptor Are Rare Events in Bladder Cancer: Implications for Therapy
Clin. Cancer Res., August 1, 2006; 12(15): 4671 - 4677.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. L. Kwak, J. Jankowski, S. P. Thayer, G. Y. Lauwers, B. W. Brannigan, P. L. Harris, R. A. Okimoto, S. M. Haserlat, D. R. Driscoll, D. Ferry, et al.
Epidermal growth factor receptor kinase domain mutations in esophageal and pancreatic adenocarcinomas.
Clin. Cancer Res., July 15, 2006; 12(14): 4283 - 4287.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
K. Erjala, M. Sundvall, T. T. Junttila, N. Zhang, M. Savisalo, P. Mali, J. Kulmala, J. Pulkkinen, R. Grenman, and K. Elenius
Signaling via ErbB2 and ErbB3 Associates with Resistance and Epidermal Growth Factor Receptor (EGFR) Amplification with Sensitivity to EGFR Inhibitor Gefitinib in Head and Neck Squamous Cell Carcinoma Cells.
Clin. Cancer Res., July 1, 2006; 12(13): 4103 - 4111.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
E. E.W. Cohen
Role of Epidermal Growth Factor Receptor Pathway-Targeted Therapy in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck
J. Clin. Oncol., June 10, 2006; 24(17): 2659 - 2665.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
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]

Home page
 Clin. Cancer Res.Home page
F. Leone, G. Cavalloni, Y. Pignochino, I. Sarotto, R. Ferraris, W. Piacibello, T. Venesio, L. Capussotti, M. Risio, and M. Aglietta
Somatic mutations of epidermal growth factor receptor in bile duct and gallbladder carcinoma.
Clin. Cancer Res., March 15, 2006; 12(6): 1680 - 1685.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
P. A. Janne, A. M. Borras, Y. Kuang, A. M. Rogers, V. A. Joshi, H. Liyanage, N. Lindeman, J. C. Lee, B. Halmos, E. A. Maher, et al.
A Rapid and Sensitive Enzymatic Method for Epidermal Growth Factor Receptor Mutation Screening
Clin. Cancer Res., February 1, 2006; 12(3): 751 - 758.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. Bruzzese, E. Di Gennaro, A. Avallone, S. Pepe, C. Arra, M. Caraglia, P. Tagliaferri, and A. Budillon
Synergistic Antitumor Activity of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Gefitinib and IFN-{alpha} in Head and Neck Cancer Cells In vitro and In vivo
Clin. Cancer Res., January 15, 2006; 12(2): 617 - 625.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. E.W. Cohen, M. A. Kane, M. A. List, B. E. Brockstein, B. Mehrotra, D. Huo, A. M. Mauer, C. Pierce, A. Dekker, and E. E. Vokes
Phase II Trial of Gefitinib 250 mg Daily in Patients with Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck
Clin. Cancer Res., December 1, 2005; 11(23): 8418 - 8424.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
E. E.W. Cohen, M. W. Lingen, L. E. Martin, P. L. Harris, B. W. Brannigan, S. M. Haserlat, R. A. Okimoto, D. C. Sgroi, S. Dahiya, B. Muir, et al.
Response of Some Head and Neck Cancers to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors May Be Linked to Mutation of ERBB2 rather than EGFR
Clin. Cancer Res., November 15, 2005; 11(22): 8105 - 8108.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. J. Wirth, R. I. Haddad, N. I. Lindeman, X. Zhao, J. C. Lee, V. A. Joshi, C. M. Norris Jr, and M. R. Posner
Phase I Study of Gefitinib Plus Celecoxib in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
J. Clin. Oncol., October 1, 2005; 23(28): 6976 - 6981.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
A. P. Dicker and U. Rodeck
Predicting the Future From Trials of the Past: Epidermal Growth Factor Receptor Expression and Outcome of Fractionated Radiation Therapy Trials
J. Clin. Oncol., August 20, 2005; 23(24): 5437 - 5439.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lee, J. W.
Right arrow Articles by Lee, S. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, J. W.
Right arrow Articles by Lee, S. H.

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