High-grade dysplasia and superficial adenocarcinoma in Barrett's esophagus: histological mapping and expression of p53, p21 and Bcl-2 oncoproteins

Abstract

In order to characterize the early morphological and molecular stages of the neoplastic progression of Barrett's mucosa, we performed the entire histological examination of ten specimens of resected Barrett's esophagus with high-grade dysplasia or superficial adenocarcinoma. The expression of p53, p21 and Bcl-2 proteins was assessed by immunohistochemistry. The surface of Barrett's mucosa ranged from 2.6 cm 2 to 31 cm 2 . Dysplasia and adenocarcinoma always developed in specialized mucosa and often occupied small surfaces. High-grade dysplasia was multifocal in eight cases. There was no preferential site for neoplastic transformation into high-grade dysplasia or superficial adenocarcinoma in Barrett's mucosa. Three superficial adenocarcinomas and four high-grade dysplasias overexpressed p53 protein. p21 protein was focally expressed in nondysplastic mucosa and overexpressed in two superficial adenocarcinomas, one high-grade dysplasia and two low-grade dysplasias. In most cases, the expression of p21 and p53 proteins was unrelated. Bcl-2 protein was detected in only one area of low-grade dysplasia. In our study, high-grade dysplasia and superficial adenocarcinoma appeared as tiny lesions, often multifocal for high-grade dysplasia confirming the need for an extensive sampling of Barrett's mucosa in the endoscopic surveillance. p53 dysfunction plays a major role in the progression from dysplasia to carcinoma in Barrett's esophagus and appears unrelated to p21 and Bcl-2 expression.

Bile Acid and Inflammation Activate Gastric Cardia Stem Cells in a Mouse Model of Barrett-Like Metaplasia

“…Our study adds to the evidence challenging the notion that metaplastic non-goblet cell CLE is entirely benign, and we would even argue that TFF2 has many advantages as a marker for BE, since it seems to be expressed early in the development of CLE, a lesion we postulate is the primary precursor lesion for EAC. Nevertheless, further studies in patients are needed to clarify the prognostic and diagnostic value of IM and CLE, since at present it remains controversial as to which metaplastic epithelial subtype best defines Barrett’s Esophagus (Chatelain and Flejou, 2003), leading to controversial risk estimates for the development of HGD or EAC in BE patients (Hvid-Jensen et al, 2011). …”

American Gastroenterological Association Technical Review on the Management of Barrett's Esophagus

“…These include difficulties in the endoscopic recognition of important lesions, 82 the random nature of esophageal biopsy sampling that is subject to considerable sampling error, 83 and disagreement among pathologists in the histologic interpretation of the esophageal biopsy specimens. 84 Finally, endoscopic examinations are expensive, especially after factoring in costs not only for the endoscopy but also for the tissue acquisition and interpretation.…”

Phase-Change Nanoparticles Using Highly Volatile Perfluorocarbons: Toward a Platform for Extravascular Ultrasound Imaging

“…The progression from Barrett's to esophageal cancer occurs through stages of low and high grade dysplasia, which are not visible to the naked eye. Currently, blind four quadrant biopsies are performed at one to two cm intervals, which sample less than five percent of the Barrett's mucosa and are thus open to sampling error 74. This is particularly worrisome as the smallest areas of high grade dysplasia can be no more than a few mm in diameter).…”