Epidermal Growth Factor Receptor Signaling in Adenocarcinomas With Bronchioloalveolar Components

Inderpal S. Sarkaria, Maureen F. Zakowski, Mimi Ceppa, Michael Hezel, Michael I. Ebright, Shaokun Chuai, Ennapadam S. Venkatraman, Mark G. Kris, Valerie W. Rusch, Bhuvanesh Singh

Research output: Contribution to journalArticle

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Abstract

Background: Epidermal growth factor receptor (EGFR) has gained importance in non-small cell lung cancer given impressive responses to agents targeting this molecule, particularly in bronchioloalveolar carcinoma (BAC) and adenocarcinomas, mixed subtype, with BAC components (adeno/BAC). This study assesses EGFR signaling in these tumors. Methods: One hundred fifty tumors were classified as BAC or adeno/BAC. Tumor marker expression was determined by immunohistochemistry. Correlations with expression were examined for all tumors (BAC and adeno/BAC), and by BAC and adeno/BAC subset analyses. Results: Positive immunophenotype was observed in 40.6% of tumors for EGFR, 51.3% for p-AKT, 58.7% for p-ERK, and 28.0% for PTEN, with increased overexpression of EGFR (p = 0.025) and p-AKT (p <0.0001) in adeno/BAC. Epidermal growth factor receptor immunophenotype was greater in never-smokers (p = 0.008) and correlated with improved overall survival (p = 0.018). On subset analysis, EGFR correlated with improved overall survival (p = 0.05) and disease-free interval (p = 0.044) only in adeno/BAC. Epidermal growth factor receptor independently predicted improved disease-free interval in adeno/BAC (p = 0.03; hazard ratio, 0.47; 95% confidence interval, 0.23 to 0.94). Conclusions: Overexpression of EGFR in lung adenocarcinomas with components of BAC histology correlate with never-smoker status and improved overall survival and disease-free interval. Epidermal growth factor receptor immunophenotype may be a useful predictor of clinical outcomes in this tumor subset.

Original languageEnglish (US)
Pages (from-to)216-223
Number of pages8
JournalAnnals of Thoracic Surgery
Volume85
Issue number1
DOIs
StatePublished - Jan 2008
Externally publishedYes

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Bronchiolo-Alveolar Adenocarcinoma
Epidermal Growth Factor Receptor
Adenocarcinoma
Neoplasms
Tumor Biomarkers
Non-Small Cell Lung Carcinoma
Disease-Free Survival

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Epidermal Growth Factor Receptor Signaling in Adenocarcinomas With Bronchioloalveolar Components. / Sarkaria, Inderpal S.; Zakowski, Maureen F.; Ceppa, Mimi; Hezel, Michael; Ebright, Michael I.; Chuai, Shaokun; Venkatraman, Ennapadam S.; Kris, Mark G.; Rusch, Valerie W.; Singh, Bhuvanesh.

In: Annals of Thoracic Surgery, Vol. 85, No. 1, 01.2008, p. 216-223.

Research output: Contribution to journalArticle

Sarkaria, IS, Zakowski, MF, Ceppa, M, Hezel, M, Ebright, MI, Chuai, S, Venkatraman, ES, Kris, MG, Rusch, VW & Singh, B 2008, 'Epidermal Growth Factor Receptor Signaling in Adenocarcinomas With Bronchioloalveolar Components', Annals of Thoracic Surgery, vol. 85, no. 1, pp. 216-223. https://doi.org/10.1016/j.athoracsur.2007.07.046
Sarkaria, Inderpal S. ; Zakowski, Maureen F. ; Ceppa, Mimi ; Hezel, Michael ; Ebright, Michael I. ; Chuai, Shaokun ; Venkatraman, Ennapadam S. ; Kris, Mark G. ; Rusch, Valerie W. ; Singh, Bhuvanesh. / Epidermal Growth Factor Receptor Signaling in Adenocarcinomas With Bronchioloalveolar Components. In: Annals of Thoracic Surgery. 2008 ; Vol. 85, No. 1. pp. 216-223.
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abstract = "Background: Epidermal growth factor receptor (EGFR) has gained importance in non-small cell lung cancer given impressive responses to agents targeting this molecule, particularly in bronchioloalveolar carcinoma (BAC) and adenocarcinomas, mixed subtype, with BAC components (adeno/BAC). This study assesses EGFR signaling in these tumors. Methods: One hundred fifty tumors were classified as BAC or adeno/BAC. Tumor marker expression was determined by immunohistochemistry. Correlations with expression were examined for all tumors (BAC and adeno/BAC), and by BAC and adeno/BAC subset analyses. Results: Positive immunophenotype was observed in 40.6{\%} of tumors for EGFR, 51.3{\%} for p-AKT, 58.7{\%} for p-ERK, and 28.0{\%} for PTEN, with increased overexpression of EGFR (p = 0.025) and p-AKT (p <0.0001) in adeno/BAC. Epidermal growth factor receptor immunophenotype was greater in never-smokers (p = 0.008) and correlated with improved overall survival (p = 0.018). On subset analysis, EGFR correlated with improved overall survival (p = 0.05) and disease-free interval (p = 0.044) only in adeno/BAC. Epidermal growth factor receptor independently predicted improved disease-free interval in adeno/BAC (p = 0.03; hazard ratio, 0.47; 95{\%} confidence interval, 0.23 to 0.94). Conclusions: Overexpression of EGFR in lung adenocarcinomas with components of BAC histology correlate with never-smoker status and improved overall survival and disease-free interval. Epidermal growth factor receptor immunophenotype may be a useful predictor of clinical outcomes in this tumor subset.",
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AU - Sarkaria, Inderpal S.

AU - Zakowski, Maureen F.

AU - Ceppa, Mimi

AU - Hezel, Michael

AU - Ebright, Michael I.

AU - Chuai, Shaokun

AU - Venkatraman, Ennapadam S.

AU - Kris, Mark G.

AU - Rusch, Valerie W.

AU - Singh, Bhuvanesh

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Y1 - 2008/1

N2 - Background: Epidermal growth factor receptor (EGFR) has gained importance in non-small cell lung cancer given impressive responses to agents targeting this molecule, particularly in bronchioloalveolar carcinoma (BAC) and adenocarcinomas, mixed subtype, with BAC components (adeno/BAC). This study assesses EGFR signaling in these tumors. Methods: One hundred fifty tumors were classified as BAC or adeno/BAC. Tumor marker expression was determined by immunohistochemistry. Correlations with expression were examined for all tumors (BAC and adeno/BAC), and by BAC and adeno/BAC subset analyses. Results: Positive immunophenotype was observed in 40.6% of tumors for EGFR, 51.3% for p-AKT, 58.7% for p-ERK, and 28.0% for PTEN, with increased overexpression of EGFR (p = 0.025) and p-AKT (p <0.0001) in adeno/BAC. Epidermal growth factor receptor immunophenotype was greater in never-smokers (p = 0.008) and correlated with improved overall survival (p = 0.018). On subset analysis, EGFR correlated with improved overall survival (p = 0.05) and disease-free interval (p = 0.044) only in adeno/BAC. Epidermal growth factor receptor independently predicted improved disease-free interval in adeno/BAC (p = 0.03; hazard ratio, 0.47; 95% confidence interval, 0.23 to 0.94). Conclusions: Overexpression of EGFR in lung adenocarcinomas with components of BAC histology correlate with never-smoker status and improved overall survival and disease-free interval. Epidermal growth factor receptor immunophenotype may be a useful predictor of clinical outcomes in this tumor subset.

AB - Background: Epidermal growth factor receptor (EGFR) has gained importance in non-small cell lung cancer given impressive responses to agents targeting this molecule, particularly in bronchioloalveolar carcinoma (BAC) and adenocarcinomas, mixed subtype, with BAC components (adeno/BAC). This study assesses EGFR signaling in these tumors. Methods: One hundred fifty tumors were classified as BAC or adeno/BAC. Tumor marker expression was determined by immunohistochemistry. Correlations with expression were examined for all tumors (BAC and adeno/BAC), and by BAC and adeno/BAC subset analyses. Results: Positive immunophenotype was observed in 40.6% of tumors for EGFR, 51.3% for p-AKT, 58.7% for p-ERK, and 28.0% for PTEN, with increased overexpression of EGFR (p = 0.025) and p-AKT (p <0.0001) in adeno/BAC. Epidermal growth factor receptor immunophenotype was greater in never-smokers (p = 0.008) and correlated with improved overall survival (p = 0.018). On subset analysis, EGFR correlated with improved overall survival (p = 0.05) and disease-free interval (p = 0.044) only in adeno/BAC. Epidermal growth factor receptor independently predicted improved disease-free interval in adeno/BAC (p = 0.03; hazard ratio, 0.47; 95% confidence interval, 0.23 to 0.94). Conclusions: Overexpression of EGFR in lung adenocarcinomas with components of BAC histology correlate with never-smoker status and improved overall survival and disease-free interval. Epidermal growth factor receptor immunophenotype may be a useful predictor of clinical outcomes in this tumor subset.

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