Evaluation of the Cell Proliferation Expansion in the Columnar Mucosa of the Distal Esophagus in Patients with Gerd: Immunohistochemical Analysis of Ki67 (Mib1) Antigen in Columnar Mucosa with and Without Intestinal Metaplasia
Marcelo Binato1,2, Renato B. Fagundes4, Luise Meurer3, Maria Isabel a. Edelweiss3, Richard R. Gurski*2
1General Surgery, UFSM, Santa Maria, Brazil; 2General Surgery, UFRGS, Porto Alegre, Brazil; 3Pathology, UFRGS, Porto Alegre, Brazil; 4Gastroenterology, UFSM, Porto Alegre, Brazil
Introduction: Columnar mucosa without intestinal metaplasia in distal esophagus is considered to be the stage that precedes the metaplasia—dysplasia—adenocarcinoma sequence. In 20% of these cases, upper endoscopy and biopsy shall confirm diagnosis of intestinal metaplasia in subsequent tests. Histology alone cannot establish the percentage of patients that will develop intestinalization of columnar mucosa. Therefore, it is necessary to seek molecular markers capable of predicting progression to more severe stages of the disease.Objectives: Determine the proliferative activity of columnar mucosa in patients with gastroesophageal reflux subjected to digestive endoscopy and biopsy in the Unit of Digestive Endoscopy of Hospital Universitário de Santa Maria, between 2003 and 2006.
Methods: The Ki67 antigen was assessed by immunohistochemical technique with use of monoclonal antibody Ki67 (MIB1) in the 1:400 dilution. Proliferative activity was determined by the Ki67 index in every proliferative compartment of the intestinal crypt (lower layer, middle layer and epithelial surface). The 62 patients who had columnar mucosa in the distal esophagus were divided into two groups: G1: 30 patients with columnar epithelium without intestinal metaplasia and G2: 32 patients with columnar epithelium with intestinal metaplasia.
Results: In G1, proliferative activity of the Ki67 was limited to the lower layer of the gland in 83% of the patients, 3% showed positive reactivity up to the middle layer and 13% showed immunoreactivity up to the epithelial surface of the esophageal crypt. In G2, proliferative activity of the Ki67 was limited to the lower layer of the gland in 46.9% of the patients, 21.9% showed positive reactivity up to the middle layer and 31.2% showed immunoreactivity up to the epithelial surface. A significant increase in the prevalence of proliferative activity in the compartments above the lower layer of the gland in patients with metaplastic columnar mucosa was found (p<0.001).
Conclusion: The expansion of cell proliferation was significantly associated to the process of intestinalization of the columnar mucosa in the distal esophagus. Therefore, the presence of proliferative activity above the lower layer of the intestinal crypt in patients with columnar mucosa may assist in the identification of patients more prone to malignant transformation of the gastric mucosa or intestinalization and, consequently, at a greater risk of disease progression (metaplasia—dysplasia—adenocarcinoma sequence).Keywords: Ki67 (MIB1). Barrett’s esophagus. Columnar mucosa. Intestinal metaplasia.