Epidermal Growth Factor Receptor, p53 Mutation, and Pathological Response Predict Survival in Patients with Locally Advanced Esophageal Cancer Treated with Preoperative Chemoradiotherapy

Michael K. Gibson, Susan C. Abraham, Tsung Teh Wu, Barbara Burtness, Richard F. Heitmiller, Elisabeth Heath, Arlene Forastiere

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Purpose: Despite the availability of cellular markers associated with cell cycle, apoptosis, and DNA repair, predictive factors for pathological complete response (CR) and overall survival (OS) are few in patients with locally advanced esophageal cancer. This study evaluates the role of clinical and cellular markers in predicting CR and OS in patients with esophageal cancer. Experimental Design: Patients were treated with infusional cisplatin and 5-fluorouracil combined with daily radiotherapy followed by esophagectomy. Pretreatment tumors (n = 54) were analyzed for epidermal growth factor receptor (EGF-R), bax, and bcl-2 expression by immunohistochemistry and for p53 mutations by direct DNA sequencing of exons 5-8. Clinical covariates included patients' age at enrollment; gender; Barrett's metaplasia; and tumor location, histology, and differentiation. Logistic regression and survival analyses were used to evaluate the predictors. Results: Age ranged from 32 to 75 years; most patients were male (45 male; 9 female); and tumors were distal (47 distal; 7 mid), adenocarcinoma (41 adenocarcinomas; 13 squamous cell carcinomas), and moderately differentiated (33 moderate; 6 well; 15 poor). Female gender predicted CR (odds ratio 7.5; 95% confidence interval, 1.4-41). The OS was 43% at 5 years. Presence of CR (P < 0.001 log rank) and p53 mutation (P = 0.051 log rank) correlated with increased OS, whereas increased EGF-R expression predicted poor OS (P = 0.009 log rank). EGF-R remained significant when adjusted for clinical covariates. There was a trend toward increased OS related to better tumor differentiation and decreased bcl-2. Conclusions: These data suggest that EGF-R and p53 mutation may be used as both outcome predictors and targets for molecular therapy for esophageal cancer.

Original languageEnglish (US)
Pages (from-to)6461-6468
Number of pages8
JournalClinical Cancer Research
Volume9
Issue number17
StatePublished - Dec 15 2003
Externally publishedYes

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Chemoradiotherapy
Esophageal Neoplasms
Epidermal Growth Factor Receptor
Mutation
Survival
Neoplasms
Adenocarcinoma
Esophagectomy
Barrett Esophagus
Survival Analysis
DNA Sequence Analysis
Fluorouracil
DNA Repair
Cisplatin
Squamous Cell Carcinoma
Exons
Histology
Cell Cycle
Research Design
Radiotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Epidermal Growth Factor Receptor, p53 Mutation, and Pathological Response Predict Survival in Patients with Locally Advanced Esophageal Cancer Treated with Preoperative Chemoradiotherapy. / Gibson, Michael K.; Abraham, Susan C.; Wu, Tsung Teh; Burtness, Barbara; Heitmiller, Richard F.; Heath, Elisabeth; Forastiere, Arlene.

In: Clinical Cancer Research, Vol. 9, No. 17, 15.12.2003, p. 6461-6468.

Research output: Contribution to journalArticle

Gibson, Michael K. ; Abraham, Susan C. ; Wu, Tsung Teh ; Burtness, Barbara ; Heitmiller, Richard F. ; Heath, Elisabeth ; Forastiere, Arlene. / Epidermal Growth Factor Receptor, p53 Mutation, and Pathological Response Predict Survival in Patients with Locally Advanced Esophageal Cancer Treated with Preoperative Chemoradiotherapy. In: Clinical Cancer Research. 2003 ; Vol. 9, No. 17. pp. 6461-6468.
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abstract = "Purpose: Despite the availability of cellular markers associated with cell cycle, apoptosis, and DNA repair, predictive factors for pathological complete response (CR) and overall survival (OS) are few in patients with locally advanced esophageal cancer. This study evaluates the role of clinical and cellular markers in predicting CR and OS in patients with esophageal cancer. Experimental Design: Patients were treated with infusional cisplatin and 5-fluorouracil combined with daily radiotherapy followed by esophagectomy. Pretreatment tumors (n = 54) were analyzed for epidermal growth factor receptor (EGF-R), bax, and bcl-2 expression by immunohistochemistry and for p53 mutations by direct DNA sequencing of exons 5-8. Clinical covariates included patients' age at enrollment; gender; Barrett's metaplasia; and tumor location, histology, and differentiation. Logistic regression and survival analyses were used to evaluate the predictors. Results: Age ranged from 32 to 75 years; most patients were male (45 male; 9 female); and tumors were distal (47 distal; 7 mid), adenocarcinoma (41 adenocarcinomas; 13 squamous cell carcinomas), and moderately differentiated (33 moderate; 6 well; 15 poor). Female gender predicted CR (odds ratio 7.5; 95{\%} confidence interval, 1.4-41). The OS was 43{\%} at 5 years. Presence of CR (P < 0.001 log rank) and p53 mutation (P = 0.051 log rank) correlated with increased OS, whereas increased EGF-R expression predicted poor OS (P = 0.009 log rank). EGF-R remained significant when adjusted for clinical covariates. There was a trend toward increased OS related to better tumor differentiation and decreased bcl-2. Conclusions: These data suggest that EGF-R and p53 mutation may be used as both outcome predictors and targets for molecular therapy for esophageal cancer.",
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AU - Gibson, Michael K.

AU - Abraham, Susan C.

AU - Wu, Tsung Teh

AU - Burtness, Barbara

AU - Heitmiller, Richard F.

AU - Heath, Elisabeth

AU - Forastiere, Arlene

PY - 2003/12/15

Y1 - 2003/12/15

N2 - Purpose: Despite the availability of cellular markers associated with cell cycle, apoptosis, and DNA repair, predictive factors for pathological complete response (CR) and overall survival (OS) are few in patients with locally advanced esophageal cancer. This study evaluates the role of clinical and cellular markers in predicting CR and OS in patients with esophageal cancer. Experimental Design: Patients were treated with infusional cisplatin and 5-fluorouracil combined with daily radiotherapy followed by esophagectomy. Pretreatment tumors (n = 54) were analyzed for epidermal growth factor receptor (EGF-R), bax, and bcl-2 expression by immunohistochemistry and for p53 mutations by direct DNA sequencing of exons 5-8. Clinical covariates included patients' age at enrollment; gender; Barrett's metaplasia; and tumor location, histology, and differentiation. Logistic regression and survival analyses were used to evaluate the predictors. Results: Age ranged from 32 to 75 years; most patients were male (45 male; 9 female); and tumors were distal (47 distal; 7 mid), adenocarcinoma (41 adenocarcinomas; 13 squamous cell carcinomas), and moderately differentiated (33 moderate; 6 well; 15 poor). Female gender predicted CR (odds ratio 7.5; 95% confidence interval, 1.4-41). The OS was 43% at 5 years. Presence of CR (P < 0.001 log rank) and p53 mutation (P = 0.051 log rank) correlated with increased OS, whereas increased EGF-R expression predicted poor OS (P = 0.009 log rank). EGF-R remained significant when adjusted for clinical covariates. There was a trend toward increased OS related to better tumor differentiation and decreased bcl-2. Conclusions: These data suggest that EGF-R and p53 mutation may be used as both outcome predictors and targets for molecular therapy for esophageal cancer.

AB - Purpose: Despite the availability of cellular markers associated with cell cycle, apoptosis, and DNA repair, predictive factors for pathological complete response (CR) and overall survival (OS) are few in patients with locally advanced esophageal cancer. This study evaluates the role of clinical and cellular markers in predicting CR and OS in patients with esophageal cancer. Experimental Design: Patients were treated with infusional cisplatin and 5-fluorouracil combined with daily radiotherapy followed by esophagectomy. Pretreatment tumors (n = 54) were analyzed for epidermal growth factor receptor (EGF-R), bax, and bcl-2 expression by immunohistochemistry and for p53 mutations by direct DNA sequencing of exons 5-8. Clinical covariates included patients' age at enrollment; gender; Barrett's metaplasia; and tumor location, histology, and differentiation. Logistic regression and survival analyses were used to evaluate the predictors. Results: Age ranged from 32 to 75 years; most patients were male (45 male; 9 female); and tumors were distal (47 distal; 7 mid), adenocarcinoma (41 adenocarcinomas; 13 squamous cell carcinomas), and moderately differentiated (33 moderate; 6 well; 15 poor). Female gender predicted CR (odds ratio 7.5; 95% confidence interval, 1.4-41). The OS was 43% at 5 years. Presence of CR (P < 0.001 log rank) and p53 mutation (P = 0.051 log rank) correlated with increased OS, whereas increased EGF-R expression predicted poor OS (P = 0.009 log rank). EGF-R remained significant when adjusted for clinical covariates. There was a trend toward increased OS related to better tumor differentiation and decreased bcl-2. Conclusions: These data suggest that EGF-R and p53 mutation may be used as both outcome predictors and targets for molecular therapy for esophageal cancer.

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