Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas

Christine H. Chung, Kim Ely, Loris McGavran, Marileila Varella-Garcia, Joel Parker, Natalie Parker, Carolyn Jarrett, Jesse Carter, Barbara A. Murphy, James Netterville, Brian B. Burkey, Robert Sinard, Anthony Cmelak, Shawn Levy, Wendell G. Yarbrough, Robbert J C Slebos, Fred R. Hirsch

Research output: Contribution to journalArticle

Abstract

Purpose: High epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC. Patients and Methods: EGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points. Results: Forty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P <.05 and P <.01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors. Conclusion: High EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.

Original languageEnglish (US)
Pages (from-to)4170-4176
Number of pages7
JournalJournal of Clinical Oncology
Volume24
Issue number25
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

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erbB-1 Genes
Gene Dosage
Fluorescence In Situ Hybridization
Epidermal Growth Factor Receptor
RNA
Carcinoma, squamous cell of head and neck
Neoplasms
Mutation
NF-kappa B
Gene Amplification
Oligonucleotide Array Sequence Analysis
Disease-Free Survival
Lung Neoplasms
Proteins
Immunohistochemistry
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. / Chung, Christine H.; Ely, Kim; McGavran, Loris; Varella-Garcia, Marileila; Parker, Joel; Parker, Natalie; Jarrett, Carolyn; Carter, Jesse; Murphy, Barbara A.; Netterville, James; Burkey, Brian B.; Sinard, Robert; Cmelak, Anthony; Levy, Shawn; Yarbrough, Wendell G.; Slebos, Robbert J C; Hirsch, Fred R.

In: Journal of Clinical Oncology, Vol. 24, No. 25, 01.09.2006, p. 4170-4176.

Research output: Contribution to journalArticle

Chung, CH, Ely, K, McGavran, L, Varella-Garcia, M, Parker, J, Parker, N, Jarrett, C, Carter, J, Murphy, BA, Netterville, J, Burkey, BB, Sinard, R, Cmelak, A, Levy, S, Yarbrough, WG, Slebos, RJC & Hirsch, FR 2006, 'Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas', Journal of Clinical Oncology, vol. 24, no. 25, pp. 4170-4176. https://doi.org/10.1200/JCO.2006.07.2587
Chung, Christine H. ; Ely, Kim ; McGavran, Loris ; Varella-Garcia, Marileila ; Parker, Joel ; Parker, Natalie ; Jarrett, Carolyn ; Carter, Jesse ; Murphy, Barbara A. ; Netterville, James ; Burkey, Brian B. ; Sinard, Robert ; Cmelak, Anthony ; Levy, Shawn ; Yarbrough, Wendell G. ; Slebos, Robbert J C ; Hirsch, Fred R. / Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 25. pp. 4170-4176.
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T1 - Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas

AU - Chung, Christine H.

AU - Ely, Kim

AU - McGavran, Loris

AU - Varella-Garcia, Marileila

AU - Parker, Joel

AU - Parker, Natalie

AU - Jarrett, Carolyn

AU - Carter, Jesse

AU - Murphy, Barbara A.

AU - Netterville, James

AU - Burkey, Brian B.

AU - Sinard, Robert

AU - Cmelak, Anthony

AU - Levy, Shawn

AU - Yarbrough, Wendell G.

AU - Slebos, Robbert J C

AU - Hirsch, Fred R.

PY - 2006/9/1

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N2 - Purpose: High epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC. Patients and Methods: EGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points. Results: Forty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P <.05 and P <.01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors. Conclusion: High EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.

AB - Purpose: High epidermal growth factor receptor (EGFR) gene copy number is associated with poor prognosis in lung cancer, but such findings have not been reported for HNSCC. A better understanding of the EGFR pathway may improve the use of EGFR inhibitors in HNSCC. Patients and Methods: EGFR status was analyzed in 86 tumor samples from 82 HNSCC patients by fluorescent in situ hybridization (FISH) to determine EGFR gene copy number, by polymerase chain reaction and direct sequencing for activating mutations, and by DNA microarray and immunohistochemistry for RNA and protein expression. The results were associated with patient characteristics and clinical end points. Results: Forty-three (58%) of 75 samples with FISH results demonstrated EGFR high polysomy and/or gene amplification (FISH positive). The FISH-positive group did not differ from the FISH-negative group with respect to age, sex, race, tumor grade, subsites and stage, or EGFR expression by analyses of RNA or protein. No activating EGFR mutations were found. However, the FISH-positive group was associated with worse progression-free and overall survival (P <.05 and P <.01, respectively; log-rank test). When microarray data were interrogated using the FISH results as a supervising parameter, ECop (which is known to coamplify with EGFR and regulate nuclear factor-kappa B transcriptional activity) had higher expression in FISH-positive tumors. Conclusion: High EGFR gene copy number by FISH is frequent in HNSCC and is a poor prognostic indicator. Additional investigation is indicated to determine the biologic significance and implications for EGFR inhibitor therapies in HNSCC.

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