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[Cancer Research 62, 7350-7356, December 15, 2002]
© 2002 American Association for Cancer Research

Tumor Biology

Impact of Epidermal Growth Factor Receptor Expression on Survival and Pattern of Relapse in Patients with Advanced Head and Neck Carcinoma1

K. Kian Ang2, Brian A. Berkey, Xiaoyu Tu, Hua-Zhong Zhang, Ruth Katz, Elizabeth H. Hammond, Karen K. Fu and Luka Milas

Departments of Radiation Oncology [K. K. A.], Experimental Radiation Oncology [X. T., L. M.], Anatomical Pathology Services Cytology [H-Z. Z.], and Pathology–Patient Care [R. K.] and Radiation Therapy Oncology Group [B. A. B.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030; Department of Pathology, LDS Hospital, University of Utah School of Medicine, Salt Lake City, Utah 84143 [E. H. H.]; and Department of Radiation Oncology, University of California, San Francisco, California 94143 [K. K. F.]

A correlative study was performed to address the impact of epidermal growth factor receptor (EGFR) overexpression on survival and pattern of failure in patients with advanced head and neck squamous cell carcinomas (HNSCCs) enrolled in a Phase III trial and randomized to receive conventional radiotherapy. The study population comprised 155 of 268 (58%) randomized patients with sufficient pretreatment biopsy specimens for immunohistochemical assay. The specimens were dewaxed and incubated after standard preparation with mouse monoclonal antibodies recognizing the extracellular domain of the EGFR molecule. The catalyzed product was visualized with 3,3'-diaminobenzidine Chromogen Kit and lightly counterstained with Mayer’s hematoxylin. Quantitative EGFR immunohistochemistry (IHC) was done with SAMBA 4000 Cell Image Analysis System, without knowledge of the clinical outcome, to yield mean absorbance (MOD), staining index (SI), and quick score (QS). These EGFR IHC parameters were correlated with the T stage, N stage, combined stage grouping, and recursive partitioning analysis classes. Subsequently, the EGFR parameters were correlated with the outcome end points, i.e., overall survival (OS), disease-free survival (DFS), local-regional (LR) relapse, and distant metastasis rates. We found that HNSCCs exhibited a wide variation in EGFR expression (MOD, 0.2–66.0; SI, 0.3–97.0; QS, 0.01–69.9) with a relatively strong but nonlinear correlation between MOD and SI (r = 0.79). There was no correlation between EGFR expression and T stage, N stage, stage grouping, and recursive partitioning analysis classes (r = -0.07 to 0.17). The OS and DFS rates of patients with high EGFR-expressing HNSCCs (>median MOD) were highly significantly lower (P = 0.0006 and P = 0.0016, respectively) and the LR relapse rate was highly significantly higher (P = 0.0031) compared with those of patients with low EGFR-expressing HNSCCs. However, there was no difference in the distant metastasis rate between the two groups (P = 0.96). Significant correlations, although somewhat less robust than MOD, were also observed between SI and QS and the OS, DFS, and LR relapse rates. Multivariate analysis showed that EGFR expression was an independent determinant of survival and a robust independent predictor of LR relapse. In summary, this correlative study in a large series of patients revealed that EGFR expression, which varied considerably among HNSCCs, was a strong independent prognostic indicator for OS and DFS and a robust predictor for LR relapse but not for distant metastasis. The data suggest that EGFR IHC should be considered for selecting patients for more aggressive combined therapies or enrollment into trials targeting EGFR signaling pathways.




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 Ann OncolHome page
P. M. Harari
Promising new advances in head and neck radiotherapy
Ann. Onc., January 1, 2005; 16(suppl_6): vi13 - vi19.
[Abstract] [Full Text] [PDF]

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 Ann OncolHome page
J. Bourhis
New approaches to enhance chemotherapy in SCCHN
Ann. Onc., January 1, 2005; 16(suppl_6): vi20 - vi24.
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 Ann OncolHome page
E. Vokes
Current treatments and promising investigations in a multidisciplinary setting
Ann. Onc., January 1, 2005; 16(suppl_6): vi25 - vi30.
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 JCOHome page
K. K. Ang
Concurrent Radiation Chemotherapy for Locally Advanced Head and Neck Carcinoma: Are We Addressing Burning Subjects?
J. Clin. Oncol., December 1, 2004; 22(23): 4657 - 4659.
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 Arch Otolaryngol Head Neck SurgHome page
D. L. Schwartz, J. Rajendran, B. Yueh, M. D. Coltrera, M. LeBlanc, J. Eary, and K. Krohn
FDG-PET Prediction of Head and Neck Squamous Cell Cancer Outcomes
Arch Otolaryngol Head Neck Surg, December 1, 2004; 130(12): 1361 - 1367.
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 Clin. Cancer Res.Home page
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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 JNMHome page
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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 Clin. Cancer Res.Home page
J. L. Dominguez-Escrig, J. D. Kelly, D. E. Neal, S. M. King, and B. R. Davies
Evaluation of the Therapeutic Potential of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Gefitinib in Preclinical Models of Bladder Cancer
Clin. Cancer Res., July 15, 2004; 10(14): 4874 - 4884.
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 JCOHome page
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.
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 Cancer Res.Home page
S. Ke, X. Wen, M. Gurfinkel, C. Charnsangavej, S. Wallace, E. M. Sevick-Muraca, and C. Li
Near-Infrared Optical Imaging of Epidermal Growth Factor Receptor in Breast Cancer Xenografts
Cancer Res., November 15, 2003; 63(22): 7870 - 7875.
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 Clin. Cancer Res.Home page
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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