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Biology of adenocarcinomas of the esphagus and stomach

ABSTRACT: Patients were recruited at the Departments of Abdominal Surgery and Endoscopy of the Hospital do Cancer AC Camargo (São Paulo/Brazil) during a 4-year period (2001 to 2004). All patients signed a pre-informed consent and the study was approved by the internal ethics committee. Tissue samples were either snap frozen in liquid nitrogen (when obtained by surgery) or collected in RNAlaterTM (Ambion®, Austin, Texas USA, when obtained by biopsy). For all samples, diagnosis was confirmed by H&E staining at the time of RNA extraction. Biopsy samples of the esophageal and gastric mucosa obtained by endoscopy had information of the correct anatomical location using a standard diagram. Frozen samples were dissected and only those having at least 70% of tumor cells were processed. A total of 71 samples were analyzed: 39 esophagus and esophagogastric junction samples (9 normal mucosa, 6 esophagitis mucosa, 10 Barrett's mucosa - 4 for the long type and 6 for the short type, and 14 tumor samples of adenocarcinoma) and 32 stomach samples (6 normal body and antrum mucosa, 5 normal cardiac mucosa, 9 intestinal metaplasia mucosa, 7 samples of intestinal type adenocarcinoma and 5 samples of diffuse type carcinoma). For Barrett's samples, diagnosis required evidence of intestinal metaplasia together with tongues or segments of red columnar-appearing epithelium extending upwards from the esophagogastric junction. A long Barrett's esophagus was defined as longer ?3cm and a short Barrett's esophagus by ?3cm of columnar epithelium (Spechler, 2004). The tumor samples of esophagus and esophagogastric junction were not differentiated. For the gastric adenocarcinoma samples were used the Laurén's classification (Laurén, 1965) and the others gastric sample were previously described (Meireles et al, 2003). Keywords: other

ORGANISM(S): Homo sapiens

PROVIDER: GSE2444 | GEO | 2005/05/09

SECONDARY ACCESSION(S): PRJNA92649

REPOSITORIES: GEO

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Project description:Barrett's esophagus is characterized by the replacement of squamous epithelium with specialized intestinal metaplastic mucosa. The exact mechanisms of initiation and development of Barrett's metaplasia remain unknown, but a hypothesis of successful adaptation against noxious reflux components has been proposed. To search for the repertoire of adaptation mechanisms of Barrett's metaplasia, we employed high-throughput functional genomic and proteomic methods that defined the molecular background of metaplastic mucosa resistance to reflux. Transcriptional profiling was established for 23 pairs of esophageal squamous epithelium and Barrett's metaplasia tissue samples using Affymetrix U133A 2.0 GeneChips and validated by quantitative real-time polymerase chain reaction. Differences in protein composition were assessed by electrophoretic and mass-spectrometry-based methods. Among 2,822 genes differentially expressed between Barrett's metaplasia and squamous epithelium, we observed significantly overexpressed metaplastic mucosa genes that encode cytokines and growth factors, constituents of extracellular matrix, basement membrane and tight junctions, and proteins involved in prostaglandin and phosphoinositol metabolism, nitric oxide production, and bioenergetics. Their expression likely reflects defense and repair responses of metaplastic mucosa, whereas overexpression of genes encoding heat shock proteins and several protein kinases in squamous epithelium may reflect lower resistance of normal esophageal epithelium than Barrett's metaplasia to reflux components. Despite the methodological and interpretative difficulties in data analyses discussed in this paper, our studies confirm that Barrett's metaplasia may be regarded as a specific microevolution allowing for accumulation of mucosal morphological and physiological changes that better protect against reflux injury. Department of Gastroenterology, Medical Center for Postgraduate Education and Maria SkM-EM-^Bodowska-Curie Memorial Cancer Center and Institute of Oncology, 02-781 Warsaw, Poland 2 types of tissue sample derived from the same patient: > Normal squamous epithelium (NE) from patients with longsegment of BarretM-bM-^@M-^Ys epithelium > Metaplastic epithelium from BarrettM-bM-^@M-^Ys esophagus (BE)

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Biology of adenocarcinomas of the esphagus and stomach

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