title: c-Myc overexpression is strongly associated with metaplasia-dysplasia-adenocarcinoma sequence in the esophagus.
abstract: We aim to determine the expression of the proto-oncogene c-Myc in patients with Barrett's esophagus (BE) and esophageal adenocarcinoma, and to evaluate the prevalence of such expression in relation to the metaplasia-dysplasia-adenocarcinoma sequence. BE develops as a result of a severe esophageal mucosa injury from gastroesophageal reflux. BE is a premalignant lesion and plays an important role in the development of esophageal adenocarcinoma. Several genetic alterations have been identified in the process that transforms a normal cell into a tumorous one. In the development of human tumors, one of the most important genes is the proto-oncogene c-Myc. The c-Myc protein expression was determined by immunohistochemical analysis in four different groups: 31 patients with normal tissue, 43 patients with BE without dysplasia, 11 patients with dysplasia in BE and 37 patients with esophageal adenocarcinoma. The material was obtained from esophageal biopsies or the dissection of patient esophagectomy specimens. Demographic and endoscopic data (sex, age, race and intestinal metaplasia extension), and morphologic and histopathologic tumor characteristics (deep tumor invasion, lymph node status, and tumor differentiation) were analyzed. The c-Myc expression was assessed using the Immunoreactive Scoring System (IRS). Overexpression of c-Myc was found in only 9.6% of normal tissue specimens, 37.2% of Barrett's esophagus, 45.5% of BE patients with dysplasia and 73% of adenocarcinoma samples, with significant statistical difference among these groups. No correlation was identified when the c-Myc expression was compared with morphologic and histologic tumor features or endoscopic data. However, linear correlation of c-Myc overexpression along the metaplasia-dysplasia-adenocarcinoma sequence was observed. This study demonstrates a significant increase in the expression of c-Myc in Barrett's esophagus, dysplasia and adenocarcinoma in relation to the control group, as well as a linear progression of this gene expression in this sequence. These results point out the importance of this marker in the development of esophageal adenocarcinoma from BE.
authors.affiliation: General Surgery Department of Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, and School of Medicine-Federal University of Rio Grande do Sul, Brazil. mkschmidt@redemeta.com.br
authors.forename: M K
authors.initials: MK
authors.lastname: Schmidt
authors.forename: L
authors.initials: L
authors.lastname: Meurer
authors.forename: B S
authors.initials: BS
authors.lastname: Volkweis
authors.forename: M I
authors.initials: MI
authors.lastname: Edelweiss
authors.forename: C C
authors.initials: CC
authors.lastname: Schirmer
authors.forename: C D P
authors.initials: CD
authors.lastname: Kruel
authors.forename: R R
authors.initials: RR
authors.lastname: Gurski
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
chemical_list: C000715470:MAS1 protein, human; C489427:MYC protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc