Interinstitutional variability and effect of tissue fixative on the interpretation of a Barrett cytokeratin 7/20 immunoreactivity pattern in Barrett esophagus
ABSTRACT A unique pattern of cytokeratin (CK) 7/20 immunostaining (diffuse staining with CK7 and surface and superficial crypt staining with CK20) has been reported to be useful in differentiating Barrett esophagus (BE) from intestinal metaplasia of the stomach. However, there are conflicting results regarding the prevalence of a BE CK7/20 staining pattern in BE between different studies. Therefore, this study was performed to determine the degree of variability in interpretation of a BE CK7/20 pattern and to determine the reasons for variability when present. Esophageal and gastric mucosal biopsies from 67 patients with BE and antral intestinal metaplasia at 2 institutions were immunostained for CK7/20. All cases were evaluated for the presence of a BE CK7/20 pattern by 2 gastrointestinal pathologists from each institution, and the degree of agreement between institutions was determined. To determine the effect of tissue fixation and staining methods on the pattern of CK7/20 staining, unstained slides were exchanged between institutions, stained separately by each institution, and reexamined by all pathologists. There was excellent agreement on the presence of a BE CK7/20 staining pattern between pathologists at the same institution but only moderate agreement between pathologists at different institutions (71% overall, kappa = 0.58). Among BE cases, a BE CK7/20 staining pattern was identified in 50 (96%) of 52 cases by Cleveland Clinic Foundation pathologists but only 35 (67%) of 52 cases by Brigham and Women's Hospital pathologists. The major source of disagreement related to the interpretation of weak or variable CK7 staining of deep intestinalized mucosa in BE biopsies that were fixed in Hollande, but not those that were fixed in formalin. After the creation of a new set of criteria for a positive BE CK7/20 staining pattern, which took into account the effects of Hollande's fixative, the degree of agreement between pathologists at each of the 2 institutions was excellent (100%, kappa value = 1.0). Therefore, the CK7/20 staining pattern is influenced by the type of fixative used. Only a moderate level of interobserver agreement among pathologists regarding a BE CK7/20 pattern can be achieved if one is not aware of these effects. Nevertheless, specific criteria for interpretation of CK7/20 staining can be successfully applied between institutions and need to be developed before use of this technique in clinical practice.
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ABSTRACT: The rise in the incidence of esophageal adenocarcinomas has raised interest in the precursor lesion Barrett’s esophagus (BE). Carcinogenesis within BE follows a sequence of histopathologic changes. Low-grade intraepithelial neoplasia is the major risk factor for progression to high-grade intraepithelial neoplasia (HG-IN) and invasive carcinoma. Other risk factors are Barrett length and prevalence and size of associated hiatal hernias. Prevention of Barrett’s carcinogenesis by medical or surgical acid suppression has not been proven effective. Chemoprevention with nonsteroidal anti-inflammatory drugs, as well as other molecular-targeted therapies, are promising and currently under investigation. Endoscopic BE ablation is experimental and accompanied by severe side effects. Endoscopic surveillance is recommended for early detection of malignant progression. When the end point of surveillance (HG-IN or carcinoma) is reached, esophagectomy is still standard treatment, although a limited surgical or endoscopic resection can be performed with lower morbidity and favorable long-term results.Current GERD Reports 06/2008; 1(2):125-132. DOI:10.1007/s12171-007-0008-y
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ABSTRACT: The gastroesophageal junction (GEJ), which is defined as the point where the distal esophagus joins the proximal stomach (cardia), is a short anatomic area that is commonly exposed to the injurious effects of GERD and/or Helicobacter pylori infection. These disorders often lead to inflammation and intestinal metaplasia (IM) of this anatomic region. The true gastric cardia is an extremely short segment (<0.4 mm) of mucosa that is typically composed of pure mucous glands, or mixed mucous/oxyntic glands that are histologically indistinguishable from metaplastic mucinous columnar epithelium of the distal esophagus. In patients with GERD, whether physiologic or pathologic, the length of cardia-type epithelium increases and extends proximally above the level of the anatomic GEJ into the distal esophagus. Columnar metaplasia of the distal esophagus represents a squamous to columnar metaplastic reaction that develops from an esophageal stem cell and may pass through an intermediate phase characterized by the presence of a type of epithelium that possesses a mixture of squamous and columnar features, termed multilayered epithelium. In contrast, IM of the gastric cardia represents a columnar to columnar cell metaplastic reaction that develops from a gastric stem cell located in the deep foveolar compartment of the gastric mucosa. Intestinal metaplasia, particularly the incomplete type, is widely believed to represent the precursor lesion upon which dysplasia and cancer arises. The frequency of IM is probably greater in metaplastic columnar epithelium in the esophagus secondary to GERD, than in cases of true gastric carditis secondary to H. pylori, and may be a reason why there is a higher risk of carcinoma in the former compared to the latter. A variety of clinical, endoscopic, histologic, and histochemical methods can be used to distinguish GERD-induced columnar metaplasia of the distal esophagus from H. pylori-induced inflammation of true gastric cardia, and these are outlined in this review, but further controlled studies are needed to critically evaluate these techniques. Further prospective trials are needed to adequately evaluate the different etiologic and pathogenetic mechanisms and, most importantly, the risk of malignancy in these two conditions.The American Journal of Gastroenterology 09/2005; 100(8):1853-67. DOI:10.1111/j.1572-0241.2005.50096.x · 10.76 Impact Factor
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ABSTRACT: CommentaryScreening and surveillance of Barrett's esophagus has been recommended by gastroenterology professional society guidelines in hopes of decreasing the mortality rate from esophageal adenocarcinoma. Although a large number of clinicians believe in the efficacy of both screening and surveillance for Barrett's esophagus, the evidence regarding their value is primarily inferential and based on relatively weak data. Dr. Kenneth Wang examines the current recommendations for screening and surveillance of Barrett's esophagus and reviews the most recent literature assessing their utility.Grace H. Elta, MDEditorClinical Update 10/2005; DOI:10.1016/j.clinup.2005.09.001