Adenocarcinoma In Barrett's Esophagus Research Articles

Magnification endoscopy with vital dye staining for detection of a minute focus of early adenocarcinoma in Barrett's esophagus

Magnification endoscopy with vital dye staining for detection of a minute focus of early adenocarcinoma in Barrett's esophagus

Intestinal metaplasia is the probable common precursor of adenocarcinoma in barrett esophagus and adenocarcinoma of the gastric cardia.

Intestinal metaplasia in the tubular esophagus is the recognized precancerous lesion of adenocarcinoma in Barrett esophagus. However, it is not yet clear whether adenocarcinoma of the gastric cardia arises from the same premalignant lesion, i.e., intestinal metaplasia of the gastric cardia. The purpose of this study was to compare adenocarcinomas in Barrett esophagus and adenocarcinomas of the gastric cardia at an early stage, when it was more likely that intestinal metaplasia had not been completely overgrown by the tumor. The authors compared the epidemiologic, clinical, and pathologic features of early stage adenocarcinoma in Barrett esophagus and adenocarcinoma of the gastric cardia from 42 patients who underwent resection surgery. The presence of intestinal metaplasia was assessed in the resected specimens by using Alcian blue (pH 2.5) staining. Intestinal metaplasia was detected in the mucosa adjacent to neoplasia in 25 of 26 patients with adenocarcinoma in Barrett esophagus and in 11 of 16 (69%) patients with adenocarcinoma of the gastric cardia. Patient and tumor characteristics and survival were comparable in both groups. Intestinal metaplasia is a very common finding in the mucosa adjacent to early stage adenocarcinoma of the gastric cardia. Adenocarcinoma in Barrett esophagus and adenocarcinoma of the gastric cardia may represent the same disease; the former arises from longer segments of intestinal metaplasia and the latter from intestinal metaplasia of the cardia.

Expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and p53 tumor suppressor in dysplastic progression and adenocarcinoma in Barrett esophagus.

Barrett esophagus predisposes individuals to esophageal carcinoma, which develops from intermediate stages of tissue dysplasia primarily in the vicinity of the gastroesophageal junction. Understanding the cellular and molecular events in the progression of Barrett esophagus to adenocarcinoma may contribute to its early diagnosis and treatment. Mutation and overexpression of the tumor suppressor p53 have previously been observed in Barrett high grade dysplasia and adenocarcinoma. The expression of the cyclin-dependent kinase (CdK) inhibitor p21 can be up-regulated by p53, resulting in the down-regulation of cell division at the G(1)/S-phase transition. The current study examined the correlation between the expression of p21 and p53 by quantifying their levels during the progression of dysplasia and adenocarcinoma in Barrett esophageal tissues. Barrett esophageal tissue samples that were negative or indefinite for dysplasia, contained dysplasia, and contained adenocarcinoma were examined by immunohistochemistry. Paraffin embedded sections of lining and glandular epithelia were adsorbed with primary murine antibodies against human p21 or p53 followed by horseradish peroxidase secondary antibody. An immunoreactivity score for each primary antibody and section was obtained by multiplying a staining intensity factor by the percent of positively stained cells. Nuclear p21 expression was detectable immunohistochemically in Barrett esophagus that was negative for dysplasia, but it was significantly elevated (P </= 0.05) in tissues scored as indefinite for dysplasia, positive for low grade or high grade dysplasia, and positive for adenocarcinoma. Importantly, p53 expression did not parallel p21 expression. p53 levels were low in the early stages of Barrett dysplasia and were increased in high grade dysplasia and adenocarcinoma. There were no differences in p21 or p53 levels between glandular and lining epithelia in Barrett tissue throughout the histologic stages of neoplastic progression evaluated in this study. p21 expression in Barrett tissue scored as indefinite for dysplasia or low grade dysplasia was significantly elevated relative to p53 expression. Elevated levels of p21 were also observed in high grade dysplasia and adenocarcinoma, in which they do not appear to be effective in down-regulating cell division. Analysis of p21 and p53 expression may aid in the evaluation of tissue abnormalities in Barrett esophagus.

Significance of Fas and retinoblastoma protein expression during the progression of Barrett's metaplasia to adenocarcinoma.

Barrett's esophagus (BE) is a premalignant lesion characterized by replacement of normal squamous epithelium with columnar epithelium. This lesion can progress to dysplasia and adenocarcinoma. Recently, the Fas receptor and retinoblastoma (Rb) protein have been described as important mediators of apoptosis and tumor suppression, respectively. This study was undertaken to examine their expression during the progression of metaplasia to adenocarcinoma in BE. In a review of 56 adenocarcinomas arising in BE, the specimen blocks were examined using the immunohistochemical avidin-biotin-peroxidase complex technique. For each specimen, areas of normal epithelium were compared with areas of metaplasia, dysplasia, or carcinoma (when present). Monoclonal mouse anti-human antibodies were used to identify Rb protein (Rb-Ab5, 1/50 dilution; Oncogene Science) and the 40-50-kDa cell membrane Fas protein (APO-1/Fas, 1/5 dilution; DAKO Corp.). Loss of Rb staining was observed as the metaplasia progressed to dysplasia and carcinoma, indicating accumulation of unstainable aberrant protein. Conversely, Fas protein staining was undetectable or weak in normal or metaplastic epithelium, increasing in the areas of high-grade dysplasia and carcinoma. These differences were statistically significant (P < .001). The accumulation of abnormal Rb protein during the progression of Barrett's metaplasia to carcinoma leads to unsuppressed tumor growth. Fas overexpression may represent a cellular attempt to balance the uncontrolled tumor proliferation by promoting apoptosis.

Barrett食道に発生した早期食道腺癌の1例―Barrett上皮の発癌に関する考察―

症例は48歳男性で，胸部不快感，嚥下困難にて来院した。食道内視鏡検査にて下部食道に発赤部位を認め，滑脱型ヘルニアも認めた。発赤部位の中に小陥凹域を認め，その部位よりの生検で高分化型管状腺癌の診断を得た。外科的切除標本では，腫瘍の大きさは5×18mmで，癌は粘膜内に留まっていた。癌は種々の程度の異型性を有する腸上皮化生により囲まれていた。以上の組織学的な検討から，最初胃粘膜に置き換えられた食道粘膜が次に腸上皮化生に置き換えられ，最後に腸上皮化生の中に腺癌が発生したと考えられた。本症例においては，胃粘膜組織は萎縮が高度で，腺窩上皮のみ存在し，腺管はほとんど消失していた。Barrett食道に発生する腺癌の発生率は0-47％と著者により様々である。高度異型上皮は癌への変換のハイリスク状態と考えられ，生検による厳重な経過観察が必要である。

Risk factors for the development of an adenocarcinoma in columnar-lined (Barrett) esophagus

To evaluate the importance of the length of columnar-lined esophagus, sex, age, smoking, and drinking habits as risk factors for malignant degeneration, the authors performed a retrospective case-control study comparing patients with and without adenocarcinoma in Barrett esophagus. The records of 96 patients (53 male and 43 female; mean age, 61 years) with a benign columnar-lined esophagus and 62 patients (47 male and 15 female; mean age, 62 years) with an adenocarcinoma in columnar-lined esophagus referred to the Rotterdam Esophageal Tumor Study Group, diagnosed over the same period (1978-1985), were reviewed. A frequency distribution of the length of columnar-lined esophagus in both groups was made. Statistical analysis was performed with multivariate methods. The length of columnar-lined esophagus was related significantly to carcinoma: a doubling of the length resulted in a 1.7 times increased risk. Smokers had a 2.3-fold increased risk as compared with nonsmokers. Male sex as a risk factor approached statistical significance (P = 0.06). Adjusted for these risk factors, no relation between carcinoma and age or alcohol consumption was found. The risk of development of an adenocarcinoma in Barrett esophagus increased with the length of Barrett epithelium. Smoking and possibly male sex were also risk factors. The identification of these risk factors may help in developing more efficient screening programs for patients with Barrett esophagus.