title: Expression and clinical significance of epidermal growth factor receptor and insulin-like growth factor receptor 1 in patients with ampullary adenocarcinoma.
abstract: Epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF-1R) play important roles in cell proliferation, antiapoptosis, angiogenesis, and metastasis and have been used for targeted therapies for patients with advanced colorectal and lung cancers. However, the expression and function of EGFR and IGF-1R in ampullary adenocarcinoma (AA) have not been examined in detail. We examined the expression of EGFR and IGF-1R in 106 AA patients at our institution using tissue microarrays and immunohistochemistry. The results were correlated with the clinicopathological parameters and survival. Overexpression of EGFR and IGF-1R was detected in 18 (17%) and 26 (25%) of AAs, respectively. Patients with EGFR-high tumors had shorter overall survival (mean, 109.8 ± 22.3 months) than those patients whose tumors were EGFR-low in overall study population (mean, 164.2 ± 10.6 months; P = .04). Overexpression of EGFR correlated with poor overall survival in patients with intestinal-type AA (P = .01) but not in those with pancreaticobiliary-type AAs (P = .47). In multivariate analysis, EGFR overexpression was an independent prognostic factor for overall survival (P = .02). In addition, we found that overexpression of IGF-1R correlated with AAs of pancreaticobiliary histology. No additional correlation between the expression of EGFR or IGF-1R and other clinicopathological factors was observed in our patient population. Our study demonstrates that EGFR and IGF-1R appear to be overexpressed in a subset of AAs and that strong membranous expression of EGFR is an independent predictor for overall survival in patients with AA. EGFR and IGF-1R represent potential therapeutic targets for treatment of patient with AAs.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555.
authors.forename: Michelle
authors.initials: M
authors.lastname: Xia
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Overman
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Asif
authors.initials: A
authors.lastname: Rashid
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Deyali
authors.initials: D
authors.lastname: Chatterjee
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Katz
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Jason B
authors.initials: JB
authors.lastname: Fleming
authors.affiliation: Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Jeffery E
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
authors.affiliation: Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX 77030. Electronic address: hmwang@mdanderson.org.
authors.forename: Huamin
authors.initials: H
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014670:Ampulla of Vater / Q000737:chemistry* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D003138:Common Bile Duct Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000032:analysis*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; C512478:EGFR protein, human; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1
keywords: Ampullary adenocarcinoma; Cyclin D1; EGFR; IGF-1R; Survival