P53 and Ki-67 overexpression in gastroesophageal reflux disease--Barrett's esophagus and adenocarcinoma sequence.
Gastroesophageal reflux disease (GERD) is a major risk factor for the development of esophageal adenocarcinoma (ACE). Many molecular alterations occur in esophageal carcinogenesis, yet the exact mechanism of ACE development remains unknown. This study aims to determine p53 protein and Ki-67 expression in esophageal mucosa of patients with GERD and study the correlation between these markers and the progression from normal squamous epithelium to esophagitis, columnar epithelium with or without intestinal metaplasia and ACE. We analyzed p53 protein and Ki-67 expression in biopsies of 200 patients with GERD and 35 patients with ACE. Those biopsies were classified into five groups: (i) G1 normal squamous epithelium (58); (ii) G2 esophagitis (80); (iii) G3 columnar epitheliums without intestinal metaplasia (30); (iv) G4, columnar epitheliums with intestinal metaplasia (32); and (v) G5 ACEs (35). p53 protein overexpression was found in 7% (4) of G1, 37.5% (30) of G2, 30% (9) of G3, 62.5% (20) of G4, and 71.4% (25) of G5 (p < 0.001). Ki-67 index increased according to the severity of histopathological diagnoses. Ki67 index was 21.3 +/- 19.5% in G1, 38.8 +/- 24.9% in G2, 37.7 +/- 26.3% in G3, 52.8 +/- 24.6% in G4, and 57.1 +/- 25.1% in G5 (P < 0.001). Linear correlation between p53/Ki67 expression and the multistep progression from squamous epithelium to ACE was observed (P < 0.001 and P < 0.05). Our results indicate that overexpression of p53 and increased Ki-67 could be associated with the development and progression to ACE in patients with GERD.
Binato
M
M
Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil. mbinato@uol.com.br
Gurski
R R
RR
Fagundes
R B
RB
Meurer
L
L
Edelweiss
M I
MI
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D001471:Barrett Esophagus / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D016099:Endoscopy, Gastrointestinal; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D004941:Esophagitis / Q000473:pathology; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D009092:Mucous Membrane / Q000378:metabolism; D011446:Prospective Studies; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53