Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma.

BACKGROUND: Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. METHODS: We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. RESULTS: EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. CONCLUSIONS: ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.

Expressão de CDX2 e mucinas (MUC1, MUC2, MUC5AC e MUC6) em esôfago de Barrett antes e após fundoplicatura de Nissen / Expression of CDX2 and mucins (MUC1, MUC2, MUC5AC and MUC6) in Barrett's esophagus before and after Nissen fundoplication

INTRODUÇÃO: O esôfago de Barrett (EB) corresponde à substituição do epitélio escamoso por um do tipo intestinal, em resposta ao refluxo crônico nos pacientes com doença do refluxo gastroesofágico (DRGE). É um importante precursor do adenocarcinoma esofágico. A fundoplicatura de Nissen (FN) é uma cirurgia antirrefluxo que visa a reduzir a agressão à mucosa esofágica. Alterações no padrão de expressão imuno-histoquímica de mucinas e de CDX2 no EB antes e depois da FN podem ser úteis na identificação de um padrão de expressão desses marcadores e, eventualmente, na identificação de casos com risco de evolução para malignidade. OBJETIVOS: Avaliar e comparar a imunoexpressão de CDX2 e mucinas no EB de pacientes com DRGE submetidos à FN antes e após a cirurgia. MATERIAIS E MÉTODOS: Estudo retrospectivo de 25 pacientes com diagnóstico de DRGE e EB submetidos à FN, acompanhados por, pelo menos, três anos. Foram feitos análise histológica e estudo imuno-histoquímico das biópsias endoscópicas antes e após a cirurgia, comparando-se a inflamação e a imunoexpressão de MUC1, MUC2, MUC5AC, MUC6 e CDX2. Estimou-se a porcentagem de células com expressão para os marcadores estudados na mucosa de Barrett: 0%-25%, 25%-75% e 75%-100% das células positivas. Foram utilizados os testes de McNemar e Stuart-William e adotou-se o nível de 5% de significância estatística. RESULTADOS E CONCLUSÃO: Não houve diferenças significativas quanto a presença ou intensidade de inflamação, nem da imunoexpressão de mucinas e CDX2 no EB antes e após a FN. O tratamento cirúrgico não influenciou a mudança da expressão dessas glicoproteínas no EB.

INTRODUCTION: Barrett´s esophagus (BE) is characterized by the exchange of esophageal squamous epithelium for intestinal type in response to chronic reflux in patients with gastroesophageal reflux disease (GERD).It is an important precursor of esophageal adenocarcinoma. Nissen fundoplication (NF) is an antireflux surgery which aims to reduce esophageal mucosa inflammation. Changes in the immunohistochemical expression patterns of mucins (MUC1, MUC2, MUC5AC and MUC6) and CDX2 in BE before and after NF may be useful to identify the expression patterns of these markers and, possibly, to detect cases with risks of malignancy. OBJECTIVES: To investigate and compare mucin and CDX2 immunoexpression in BE patients with GERD before and after NF. MATERIAL AND METHODS: This retrospective study comprised 25 patients with GERD and BE who had been submitted to NF. The patients had a 3-year minimum follow up. Histological and immunohistochemical analyses of endoscopic biopsies were performed before and after the surgery, comparing inflammation and MUC1, MUC2, MUC5AC, MUC6 and CDX2 immunoexpression. The percentage of Barrett mucosa cells with expression to the studied markers was estimated at 0%-25%, 25%-75% and 75%-100%. McNemar and Stuart-William tests were used and the significance level of <0.05 was applied. RESULTS AND CONCLUSION: Concerning the presence or the intensity of inflammation and mucin and CDX2 expression in BE, there were no significant differences before and after NF. The surgical procedure did not promote any changes in the expression of these glycoproteins in BE.

p53 protein overexpression and p53 mutation analysis in patients with intestinal metaplasia of the cardia and Barrett's esophagus.

p53 mutation is a common genetic change in human cancers, but the clinical significance is controversial. We studied 68 patients and estimate the prevalence of intestinal metaplasia of cardia (IMC), Barrett's esophagus (BE), and p53 protein overexpression, and described molecular alterations of p53 gene exons 5 to 8. Immunohistochemical analysis showed positive p53 in 56.1-39.1% (IMC) and 60.9% (BE). Molecular analysis showed 36.6% altered cases in exon 5 and 9.8% in exon 7. In conclusion, p53 protein overexpression is common in IMC and BE. The molecular alterations observed may be due to LOH, genomic instability or other unknown alteration.