Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma

Sarah Wheeler, Doris R. Siwak, Raymond Chai, Courtney LaValle, Raja R. Seethala, Lin Wang, Kathleen Cieply, Carol Sherer, Corwin Joy, Gordon Mills, Athanassios Argiris, Jill M. Siegfried, Jennifer R. Grandis, Ann Marie Egloff

Research output: Contribution to journalArticle

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Abstract

Purpose: To assess the prognostic value of epidermal growth factor receptor (EGFR) molecular characteristics of head and neck squamous cell carcinoma (HNSCC). Patients and Methods: HNSCC tumors from patients prospectively enrolled in either an Early Detection Research Network (EDRN) study and treated with surgery without an EGFR-targeted agent (N = 154) or enrolled in a chemoradiation trial involving the EGFR-targeted antibody cetuximab (N = 39) were evaluated for EGFR gene amplification by FISH and EGFR protein by immunohistochemical staining. Fresh-frozen tumors (EDRN) were also evaluated for EGFR protein and site-specific phosphorylation at Y992 and Y1068 using reverse-phase protein array (n = 67). Tumor (n = 50) EGFR and EGFRvIII mRNA levels were quantified using real-time PCR. Results: EGFR expression by immunohistochemistry (IHC) was significantly higher in the EDRN tumors with EGFR gene amplification (P < 0.001), and a similar trend was noted in the cetuximab-treated cohort. In the EDRN and cetuximab-treated cohorts elevated EGFR by IHC was associated with reduced survival (P =0.019 and P = 0.06, respectively). Elevated expression of total EGFR and EGFR PY1068 were independently significantly associated with reduced progression-free survival in the EDRN cohort [HR = 2.75; 95% confidence interval (CI) = 1.26-6.00 and HR = 3.29; 95% CI = 1.34-8.14, respectively]. Conclusions: In two independent HNSCC cohorts treated with or without cetuximab, tumor EGFR levels were indicative of survival. Tumor EGFR PY1068 levels provided prognostic information independent of total EGFR.

Original languageEnglish (US)
Pages (from-to)2278-2289
Number of pages12
JournalClinical Cancer Research
Volume18
Issue number8
DOIs
StatePublished - Apr 15 2012
Externally publishedYes

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Epidermal Growth Factor Receptor
Neoplasms
erbB-1 Genes
Research
Gene Amplification
Carcinoma, squamous cell of head and neck
Immunohistochemistry
Confidence Intervals
Protein Array Analysis
Survival
Disease-Free Survival
Real-Time Polymerase Chain Reaction
Proteins
Phosphorylation
Staining and Labeling

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma. / Wheeler, Sarah; Siwak, Doris R.; Chai, Raymond; LaValle, Courtney; Seethala, Raja R.; Wang, Lin; Cieply, Kathleen; Sherer, Carol; Joy, Corwin; Mills, Gordon; Argiris, Athanassios; Siegfried, Jill M.; Grandis, Jennifer R.; Egloff, Ann Marie.

In: Clinical Cancer Research, Vol. 18, No. 8, 15.04.2012, p. 2278-2289.

Research output: Contribution to journalArticle

Wheeler, S, Siwak, DR, Chai, R, LaValle, C, Seethala, RR, Wang, L, Cieply, K, Sherer, C, Joy, C, Mills, G, Argiris, A, Siegfried, JM, Grandis, JR & Egloff, AM 2012, 'Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma', Clinical Cancer Research, vol. 18, no. 8, pp. 2278-2289. https://doi.org/10.1158/1078-0432.CCR-11-1593
Wheeler, Sarah ; Siwak, Doris R. ; Chai, Raymond ; LaValle, Courtney ; Seethala, Raja R. ; Wang, Lin ; Cieply, Kathleen ; Sherer, Carol ; Joy, Corwin ; Mills, Gordon ; Argiris, Athanassios ; Siegfried, Jill M. ; Grandis, Jennifer R. ; Egloff, Ann Marie. / Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 8. pp. 2278-2289.
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abstract = "Purpose: To assess the prognostic value of epidermal growth factor receptor (EGFR) molecular characteristics of head and neck squamous cell carcinoma (HNSCC). Patients and Methods: HNSCC tumors from patients prospectively enrolled in either an Early Detection Research Network (EDRN) study and treated with surgery without an EGFR-targeted agent (N = 154) or enrolled in a chemoradiation trial involving the EGFR-targeted antibody cetuximab (N = 39) were evaluated for EGFR gene amplification by FISH and EGFR protein by immunohistochemical staining. Fresh-frozen tumors (EDRN) were also evaluated for EGFR protein and site-specific phosphorylation at Y992 and Y1068 using reverse-phase protein array (n = 67). Tumor (n = 50) EGFR and EGFRvIII mRNA levels were quantified using real-time PCR. Results: EGFR expression by immunohistochemistry (IHC) was significantly higher in the EDRN tumors with EGFR gene amplification (P < 0.001), and a similar trend was noted in the cetuximab-treated cohort. In the EDRN and cetuximab-treated cohorts elevated EGFR by IHC was associated with reduced survival (P =0.019 and P = 0.06, respectively). Elevated expression of total EGFR and EGFR PY1068 were independently significantly associated with reduced progression-free survival in the EDRN cohort [HR = 2.75; 95{\%} confidence interval (CI) = 1.26-6.00 and HR = 3.29; 95{\%} CI = 1.34-8.14, respectively]. Conclusions: In two independent HNSCC cohorts treated with or without cetuximab, tumor EGFR levels were indicative of survival. Tumor EGFR PY1068 levels provided prognostic information independent of total EGFR.",
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T1 - Tumor epidermal growth factor receptor and EGFR PY1068 are independent prognostic indicators for head and neck squamous cell carcinoma

AU - Wheeler, Sarah

AU - Siwak, Doris R.

AU - Chai, Raymond

AU - LaValle, Courtney

AU - Seethala, Raja R.

AU - Wang, Lin

AU - Cieply, Kathleen

AU - Sherer, Carol

AU - Joy, Corwin

AU - Mills, Gordon

AU - Argiris, Athanassios

AU - Siegfried, Jill M.

AU - Grandis, Jennifer R.

AU - Egloff, Ann Marie

PY - 2012/4/15

Y1 - 2012/4/15

N2 - Purpose: To assess the prognostic value of epidermal growth factor receptor (EGFR) molecular characteristics of head and neck squamous cell carcinoma (HNSCC). Patients and Methods: HNSCC tumors from patients prospectively enrolled in either an Early Detection Research Network (EDRN) study and treated with surgery without an EGFR-targeted agent (N = 154) or enrolled in a chemoradiation trial involving the EGFR-targeted antibody cetuximab (N = 39) were evaluated for EGFR gene amplification by FISH and EGFR protein by immunohistochemical staining. Fresh-frozen tumors (EDRN) were also evaluated for EGFR protein and site-specific phosphorylation at Y992 and Y1068 using reverse-phase protein array (n = 67). Tumor (n = 50) EGFR and EGFRvIII mRNA levels were quantified using real-time PCR. Results: EGFR expression by immunohistochemistry (IHC) was significantly higher in the EDRN tumors with EGFR gene amplification (P < 0.001), and a similar trend was noted in the cetuximab-treated cohort. In the EDRN and cetuximab-treated cohorts elevated EGFR by IHC was associated with reduced survival (P =0.019 and P = 0.06, respectively). Elevated expression of total EGFR and EGFR PY1068 were independently significantly associated with reduced progression-free survival in the EDRN cohort [HR = 2.75; 95% confidence interval (CI) = 1.26-6.00 and HR = 3.29; 95% CI = 1.34-8.14, respectively]. Conclusions: In two independent HNSCC cohorts treated with or without cetuximab, tumor EGFR levels were indicative of survival. Tumor EGFR PY1068 levels provided prognostic information independent of total EGFR.

AB - Purpose: To assess the prognostic value of epidermal growth factor receptor (EGFR) molecular characteristics of head and neck squamous cell carcinoma (HNSCC). Patients and Methods: HNSCC tumors from patients prospectively enrolled in either an Early Detection Research Network (EDRN) study and treated with surgery without an EGFR-targeted agent (N = 154) or enrolled in a chemoradiation trial involving the EGFR-targeted antibody cetuximab (N = 39) were evaluated for EGFR gene amplification by FISH and EGFR protein by immunohistochemical staining. Fresh-frozen tumors (EDRN) were also evaluated for EGFR protein and site-specific phosphorylation at Y992 and Y1068 using reverse-phase protein array (n = 67). Tumor (n = 50) EGFR and EGFRvIII mRNA levels were quantified using real-time PCR. Results: EGFR expression by immunohistochemistry (IHC) was significantly higher in the EDRN tumors with EGFR gene amplification (P < 0.001), and a similar trend was noted in the cetuximab-treated cohort. In the EDRN and cetuximab-treated cohorts elevated EGFR by IHC was associated with reduced survival (P =0.019 and P = 0.06, respectively). Elevated expression of total EGFR and EGFR PY1068 were independently significantly associated with reduced progression-free survival in the EDRN cohort [HR = 2.75; 95% confidence interval (CI) = 1.26-6.00 and HR = 3.29; 95% CI = 1.34-8.14, respectively]. Conclusions: In two independent HNSCC cohorts treated with or without cetuximab, tumor EGFR levels were indicative of survival. Tumor EGFR PY1068 levels provided prognostic information independent of total EGFR.

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U2 - 10.1158/1078-0432.CCR-11-1593

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