The molecular pathology of Barrett's esophagus
| Autor: | Werner, M., Mueller, J., Walch, A., Hofler, H. |
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| Rok vydání: | 1999 |
| Předmět: | |
| Zdroj: | DIGITUM. Depósito Digital Institucional de la Universidad de Murcia instname |
| Popis: | The incidence of adenocarcinoma of the distal esophagus is rapidly increasing in the Western world. The histopathological sequence of (Barrett's) metaplasia, which develops as a consequence of chronic reflux, to dysplasia and then to carcinoma is well established for these tumors. In Barrett's esophagus a variety of molecular changes have been characterized and correlated with tumor initiation and progression. Among the early changes in premalignant stages of metaplasia are alterations of the transcripts of FHIT, a presumptive tumor suppressor gene which spans the common fragile site FRA3B. Mutations of p53 seem to accumulate mainly in the transition from low to high grade dysplasia. Inactivation of other tumor suppressor genes by mutation (APC, p16) or hypermethylation (p16) as well as amplification of oncogenes such as cerbB2 are relatively late events in the development of adenocarcinoma. Among the phenotypic changes in Barrett's esophagus are an expansion of the Ki67 proliferation compartment which correlates with the degree of dysplasia. Moreover, accumulation of rabll molecules which are involved in membrane trafficking has been reported to be specific for the loss of polarity seen in low grade dysplasia. Reduced expression of the cadherinlcatenin complex as well as increased expression of various proteases develop chiefly in invasive carcinomas. Despite the progress that has been made in the identification of molecular markers in Barrett's carcinoma, to date the histopathogical diagnosis of high grade dysplasia in endoscopic biopsies remains the best predictor of invasive cancer. Immunohistochemistry applying a panel of antibodies including p53, Mib-l or rabll can be helpful to diagnose regenerative metaplastic epithelium or low and high grade dysplasia. |
| Databáze: | OpenAIRE |
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