Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Epidermal Growth Factor Receptor, p53 Mutation, and Pathological Response Predict Survival in Patients with Locally Advanced Esophageal Cancer Treated with Preoperative Chemoradiotherapy
Ist Teil von
Clinical cancer research, 2003-12, Vol.9 (17), p.6461-6468
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2003
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.