Epidermal Growth Factor Receptor (EGFR) Is Overexpressed in High-Grade Dysplasia and Adenocarcinoma of the Esophagus and May Represent a Biomarker of Histological Progression in Barrett's Esophagus (BE)

Cronin, James; McAdam, Elizabeth; Danikas, Antonios; Tselepis, Chris; Griffiths, Paul; Baxter, John; Thomas, Linzi; Manson, James; Jenkins, Gareth
January 2011
American Journal of Gastroenterology;Jan2011, Vol. 106 Issue 1, p46
Academic Journal
OBJECTIVES:The assessment of cancer risk in patients with Barrett's esophagus (BE) is currently fraught with difficulty. The current gold standard method of assessing cancer risk is histological assessment, with the appearance of high-grade dysplasia (HGD) as the key event monitored. Sampling error during endoscopy limits the usefulness of this approach, and there has been much recent interest in supplementing histological assessment with molecular markers, which may aid in patient stratification.METHODS:No molecular marker has been yet validated to accurately correlate with esophageal histological progression. Here, we assessed the suitability of several membranous proteins as biomarkers by correlating their abundance with histological progression. In all, 107 patient samples, from 100 patients, were arranged on a tissue microarray (TMA) and represented the various stages of histological progression in BE. This TMA was probed with antibodies for eight receptor proteins (mostly membranous).RESULTS:Epidermal growth factor receptor (EGFR) staining was found to be the most promising biomarker identified with clear increases in staining accompanying histological progression. Further, immunohistochemistry was performed using the full-tissue sections from BE, HGD, and adenocarcinoma tissues, which confirmed the stepwise increase in EGFR abundance. Using a robust H-score analysis, EGFR abundance was shown to increase 13-fold in the adenocarcinoma tissues compared to the BE tissues. EGFR was 'overexpressed' in 35% of HGD specimens and 80% of adenocarcinoma specimens when using the H-score of the BE patients (plus 3 s.d.) as the threshold to define overexpression. EGFR staining was also noted to be higher in BE tissues adjacent to HGD/adenocarcinoma. Western blotting, although showing more EGFR protein in the adenocarcinomas compared to the BE tissue, was highly variable. EGFR overexpression was accompanied by aneuploidy (gain) of chromosome 7, plus amplification of the EGFR locus. Finally, the bile acid deoxycholic acid (DCA) (at neutral and acidic pH) and acid alone was capable of upregulating EGFR mRNA in vitro, and in the case of neutral pH DCA, this was NF-κB dependent.CONCLUSIONS:EGFR is overexpressed during the histological progression in BE tissues and hence may be useful as a biomarker of histological progression. Furthermore, as EGFR is a membranous protein expressed on the luminal surface of the esophageal mucosa, it may also be a useful target for biopsy guidance during endoscopy.


Related Articles

  • Short Segment Barrett's Esophagus: Clinical and Histological Features, Associated Endoscopic Findings, and Association with Gastric Intestinal Metaplasia. Weston, Allan P.; Krmpotich, Philip; Makdisi, Walid F.; Cherian, Rachel; Dixon, Anita; McGregor, Douglas H.; Banerjee, Sushanta K. // American Journal of Gastroenterology;May1996, Vol. 91 Issue 5, p981 

    Objectives: To prospectively determine the clinical features, associated esophageal endoscopic lesions, associated gastric intestinal metaplasia, and prevalence of dysplasia and adenocarcinoma of short segment Barrett's. Methods: All patients undergoing upper endoscopy over a 5-month period were...

  • Barrett's Esophagus, High-Grade Dysplasia, and Early Adenocarcinoma: A Pathological Study. Cameron, Alan J.; Carpenter, Herschel A. // American Journal of Gastroenterology;Apr1997, Vol. 92 Issue 4, p586 

    Objectives: In Barrett's esophagus, early adenocarcinomas are often missed on endoscopic biopsy. We therefore examined the distribution and extent of dysplasia and carcinoma in the resected esophagus for comparison with the preoperative biopsy findings. Methods: Patients whose endoscopy showed...

  • Epidermal growth factor receptor expression correlates with histologic grade in resected esophageal adenocarcinoma Wilkinson, Neal W.; Black, Jennifer D.; Roukhadze, Elena; Driscoll, Deborah; Smiley, Shannon; Hoshi, Hisakazu; Geradts, Joseph; Javle, Milind; Brattain, Michael // Journal of Gastrointestinal Surgery;May2004, Vol. 8 Issue 4, p448 

    Activation of the epidermal growth factor receptor (EGFR) has a role in oncogenesis and may correlate with prognosis. The aim of this study was to examine EGFR expression in esophageal adenocarcinoma and correlate EGFR status with pathologic and clinical prognostic features. An exploratory...

  • Epidermal Growth Factor Receptor Expression in Esophageal Adenocarcinoma: Relationship with Tumor Stage and Survival after Esophagectomy. Navarini, Daniel; Gurski, Richard R.; Madalosso, Carlos Augusto; Aita, Lucas; Meurer, Luise; Fornari, Fernando // Gastroenterology Research & Practice;2012, p1 

    Background and Aims. Esophageal adenocarcinoma (EA) is an aggressive tumor with increasing incidence in occidental countries. Several prognostic biomarkers have been proposed, including epidermal growth factor receptor (EGFR). The aim of this study was to assess whether EGFR expression predicts...

  • Phase II trial of modified FOLFOX6 and erlotinib in patients with metastatic or advanced adenocarcinoma of the oesophagus and gastro-oesophageal junction. Wainberg, Z. A.; Lin, L.-S.; DiCarlo, B.; Dao, K. M.; Patel, R.; Park, D. J.; Wang, H.-J.; Elashoff, R.; Ryba, N.; Hecht, J. R. // British Journal of Cancer;9/6/2011, Vol. 105 Issue 6, p760 

    Background: There is increased recognition that cancers of the upper GI tract comprise distinct epidemiological and molecular entities. Erlotinib has shown activity in patients with adenocarcinoma of the oesophagus/gastro-oesophageal junction (GEJ), but not in distal gastric cancer....

  • Functional single-nucleotide polymorphism of epidermal growth factor is associated with the development of Barrett's esophagus and esophageal adenocarcinoma. Menke, Vivianda; Pot, Raymond GJ; Moons, Leon MG; van Zoest, Katinka PM; Hansen, Bettina; van Dekken, Herman; Siersema, Peter D; Kusters, Johannes G; Kuipers, Ernst J // Journal of Human Genetics;Jan2012, Vol. 57 Issue 1, p26 

    Reflux esophagitis (RO) and Barrett's esophagus (BO) can cause esophageal adenocarcinoma (OAC). The esophageal mucosa in the RO-BO-OAC cascade is chronically exposed to gastro-esophageal reflux. Epidermal growth factor (EGF) has an important role in the protection and repair of mucosal damage,...

  • ADENOCARCINOMA IN SITU IN BARRETT'S ESOPHAGUS WITH STRICTURE OF 10-YR DURATION: A CYTOLOGICAL DIAGNOSIS. Bauer, William; Ali, Syed Z.; Urmacher, Carlos; Katz, Seymour // American Journal of Gastroenterology;Aug1996, Vol. 91 Issue 8, p1650 

    Discusses a cytological diagnosis of adenocarcinoma in situ in Barrett's esophagus with stricture of ten-year duration. Information on Barrett's esophagus; Overview of the medical history of the patient; Assessment of the premalignant potential for Barrett's esophagus.

  • Long-Term Survival in a Patient with Verrucous Carcinoma of the Esophagus. Malik, Amer B.; Bidani, Jatin A.; Rich, Harlan G.; McCully, Kilmer S. // American Journal of Gastroenterology;May1996, Vol. 91 Issue 5, p1031 

    A 66-yr-old white male with a long-standing history of gastroesophageal reflux and Barrett's esophagus developed squamous cell dysplasia proximal to the site of the metaplastic epithelium. Two months later, he presented with progressive dysphagia. Upper endoscopy revealed near obliteration of...

  • Lugol Staining Pattern and Histology of Esophageal Lesions. Mori, Masaki; Adachi, Yosuke; Matsushima, Tetsuya; Matsuda, Hiroyuki; Kuwano, Hiroyuki; Sugimachi, Keizo // American Journal of Gastroenterology;May1993, Vol. 88 Issue 5, p701 

    To analyze the relationship between Lugol unstained areas and their histologic features, we applied the Lugol test to 24 specimens of resected esophagus. The staining patterns were graded into four types: grade I, hyperstaining; grade II normal greenish brown staining; grade III, less intense...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics