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Background: Human chorionic gonadotrophin beta (hCGbeta) is expressed in several non-trophoblastic tumours, and this is usually associated with aggressive behaviour. Little is known about hCGbeta expression in Barrett's adenocarcinoma., Materials and Methods: We determined the hCGbeta profile in a large series of surgically resected Barrett's adenocarcinoma (a) at mRNA level using real-time quantitative reverse-transcription polymerase chain reaction analysis and (b) at protein level using immunohistochemistry with a polyclonal antibody and with a monoclonal antibody specific for free hCGbeta. We then sought links between the hCGbeta protein expression pattern and clinical and pathological parameters, including patient outcome as well as vascular endothelial growth factor (VEGF) expression., Results: hCGbeta protein expression was observed in 43 of 76 (57%) Barrett's adenocarcinomas. We showed a strong correlation between hCGbeta protein abundance and CGB mRNA level. We observed a statistical link between hCGbeta protein expression and infiltrative tumour type ( P=0.023), perineural neoplastic invasion ( P=0.007) and VEGF protein expression ( P=0.016). hCGbeta expression tended to be associated with a poor outcome (16% versus 36% survival 8 years after resection)., Conclusion: Expression of hCGbeta correlates with specific infiltrative characteristics and is associated with higher VEGF expression. Both molecules may play a co-ordinated role in the development of Barrett's adenocarcinomas.

Aims: To establish the prevalence of inflammatory secretory phospholipase A2 (sPLA2) and cytoplasmic phospholipase A2 (cPLA2) expression in a surgical series of Barrett's adenocarcinoma and associated preneoplastic lesions and to correlate this expression with clinicopathological data and prognosis., Methods: sPLA2 and cPLA2 were analysed by means of immunohistochemistry in surgical specimens of 67 and 73 cases of Barrett's adenocarcinomas, respectively. Barrett's mucosa was analysed in 31 cases., Results: Expression of sPLA2 was detected in 48% of Barrett's mucosa negative for intraepithelial neoplasia and 63% of Barrett's adenocarcinoma. Semi-quantitative analysis revealed a significant increase in sPLA2 expression between Barrett's mucosa negative for intraepithelial neoplasia and adenocarcinoma. cPLA2 expression was detected in 18% of Barrett's adenocarcinoma. An inverse correlation was found between cPLA2 expression and depth of tumour infiltration, neoplastic vascular invasion and neoplastic perineural invasion. Survival analysis showed no significant prognostic value for sPLA2 and cPLA2., Conclusion: sPLA2 is frequently expressed in Barrett's oesophagus. The increasing expression of sPLA2 that we observed from Barrett's mucosa to adenocarcinoma suggests that sPLA2 could be involved in Barrett's carcinogenesis. In contrast, cPLA2 expression is less frequently observed in Barrett's oesophagus and is inversely associated with aggressive pathological features of the tumours.

Aims: To establish the prevalence of cyclooxygenase-2 (COX-2) expression in a large series of resected Barrett's adenocarcinoma and associated preneoplastic lesions and to correlate this expression with clinicopathological data and prognosis., Methods: COX-2 expression was assessed by immunohistochemistry in resected surgical specimens of 66 Barrett's adenocarcinomas and 32 cases of Barrett's mucosa (with dysplasia in 17 cases)., Results: Epithelial expression of COX-2 protein was increased in Barrett's mucosa compared with normal oesophagus. Epithelial expression of COX-2 was found in 91% of Barrett's specialized mucosa negative for dysplasia, 94% of Barrett's mucosa with dysplasia, and 97% of Barrett's adenocarcinoma. COX-2 expression was significantly higher in the well-differentiated adenocarcinomas when compared with the poorly differentiated tumours. There was no significant correlation between COX-2 expression and the other pathological features of the tumours. Survival analysis showed no significant prognostic value for COX-2., Conclusion: Our results confirm up-regulation of COX-2 in Barrett's oesophagus-metaplastic and dysplastic-and in Barrett's adenocarcinoma. Increased COX-2 expression did not differ during the progression from Barrett's oesophagus negative for dysplasia to Barrett's adenocarcinoma and is related to adenocarcinoma whose histology is well differentiated. This suggests that enhanced expression of COX-2 may occur early during Barrett's-associated neoplastic transformation.

The purpose of this study was to determine the angiogenic profile of human oesophageal adenocarcinoma. This study was carried out on a large series of surgically resected Barrett's adenocarcinomas and associated preneoplastic lesions. Vascularization was quantified by microvessel counting and measurement of the percentage microvessel surface area after immunohistochemistry using the CD34 antibody. The expression of vascular endothelial cell growth factor (VEGF) was also examined by immunohistochemistry. Results were correlated with clinico-pathological data and prognosis. Vascularization, assessed by both microvessel counting and measurement of the microvessel surface, was statistically higher in superficial cancers than in others. Higher vascularization was correlated with a lower rate of lymph node and distant metastasis, as well as with better survival. However, when superficial carcinomas were excluded from the study, microvessel count failed to provide any significant prognostic information. Irrespective of the inclusion or exclusion of superficial tumours, the expression of VEGF was correlated with a higher vascularisation but did not provide prognostic significance. It is concluded that high angiogenic properties are acquired in precancerous lesions and early cancers in Barrett's oesophagus. Vascularization as assessed by both microvessel counting and measurement of the microvessel surface is not informative for prognosis in infiltrative Barrett's adenocarcinomas. The expression of VEGF is correlated with vascularization, but has no independent prognostic relevance., (Copyright 2000 John Wiley & Sons, Ltd.)

Aims: To establish the prevalence of CD44 protein expression in a large surgical series of Barrett's adenocarcinoma and associated preneoplastic lesions and to correlate this expression with clinicopathological data and prognosis., Methods and Results: CD44H and variants (V4/V5, V6) expression was detected by immunohistochemistry in formalin-fixed, paraffin wax tissue samples of Barrett's mucosa (50) and Barrett's adenocarcinoma (73) obtained from surgical resections from 73 patients. This expression was correlated with pathological features of the tumour and prognosis. CD44H and V6 expression was found in 62% and 55% of Barrett's specialized mucosa negative for dysplasia and in 70% and 63% of Barrett's adenocarcinoma, respectively. CD44H and V6 expression was restricted to the lower part of the crypts in Barrett's specialized mucosa negative for dysplasia and reached the upper part of the crypts in high-grade dysplasia. A significant relation was found between CD44V6 expression and depth of tumour invasion in the oesophageal wall (P = 0.05), neoplastic vascular invasion (P = 0.0001), neoplastic perineural invasion (P = 0.0004) and stage in Rosenberg's classification (P = 0.02). Cancers with CD44V6 expression had a significantly poorer prognosis (5-year survival: 17%) than those without (5-year survival: 44%) (P = 0.02) in univariate analysis. However, multivariate analysis showed that CD44V6 expression had no independent prognostic value when tumour invasion and lymph node involvement were taken as explanatory variables., Conclusion: CD44H and V6 are frequently expressed in Barrett's oesophagus. The pattern of expression that we observed from mucosa negative for dysplasia to adenocarcinoma suggests that CD44H and V6 may be involved in the carcinogenesis of Barrett's mucosa. CD44V6 expression in adenocarcinoma is correlated to aggressive pathological features.

Numerous reviews of adenocarcinoma arising in Barrett's esophagus have been reported, but detailed pathologic findings or survival analysis have rarely been provided. This retrospective study analyzed 67 patients (mean age, 64 years; male-to-female ratio, 10:1) with an adenocarcinoma arising in Barrett's esophagus treated by surgical resection. Prevalence of smokers was 63%, alcohol users, 45%, and patients with hiatal hernia, 73%. Five patients had another synchronous cancer, and seven patients, previous esophageal surgery. Forty percent of the tumors were well differentiated, 31% moderately differentiated, 15% poorly differentiated, 7% mucinous, and 6% composed of signet-ring cells. Depth of invasion in the esophageal wall was limited to mucosa in 13% of cases and submucosa in 18%. Invasive adenocarcinomas extended to the muscular layer in 12% of cases, to adventitia in 33%, and to periesophageal tissue in 24%. Vascular and perineural neoplastic invasion was present in 67 and 38% of cases. Regional lymph node involvement and distant metastases were found in 51 and 9% of cases. Overall, 1-, 2-, and 5-year survival rates were 63, 41, and 32%, respectively. Five-year survival rate was significantly better for patients with superficial cancer limited to mucosa or submucosa (82 vs. 12%) or without regional lymph node involvement (59 vs. 10%). Tumor differentiation, vascular and perineural invasion, extranodal spread, distant metastases, and resection margins status also had a significant prognostic value on univariate analysis. In a multivariate Cox regression analysis for overall survival, depth of invasion in the esophageal wall and regional lymph node involvement were independent prognostic factors. Careful pathologic staging is of value in determining the prognosis of patients with adenocarcinoma arising in Barrett's esophagus.

Aims: To establish the prevalence of c-erbB-2 protein expression in a surgical series of Barrett's adenocarcinomas; and to correlate this expression with clinicopathological data and prognosis., Methods: Sixty six surgical specimens of Barrett's adenocarcinomas were included in this retrospective study. Blocks of the tumour and of non-dysplastic Barrett's mucosa were stained with a polyclonal antibody specific for the intracytoplasmic domain of the c-erbB-2 protein., Results: Seven of 66 tumours showed membrane staining for the c-erbB-2 protein. The non-dysplastic Barrett's mucosa was negative in all cases. There was no difference between c-erbB-2 positive and negative tumours with regard to mean age, sex ratio, percentage of alcohol misusers, percentage of smokers, tumour differentiation, depth of invasion, lymph node response, and proliferative activity, assessed by the percentage of tumour cells positive with the MIB-1 antibody directed against the Ki-67 antigen. All c-erb B2 positive tumours were of Lauren's intestinal type compared with negative c-erbB-2 tumours. Patients with c-erbB-2 positive tumours had a significantly poorer prognosis than patients with negative tumours., Conclusions: The prevalence of Barrett's adenocarcinomas expressing c-erbB-2 found in this study (11%) was similar to that observed in published series of gastric adenocarcinomas. c-erbB-2 protein expression could be an important prognostic indicator in Barrett's adenocarcinoma.

Adenocarcinoma of the esophagus is a well known complication of Barrett's esophagus, and results from a dysplasia-carcinoma sequence. This report describes 3 patients with adenomatous polyps arising in Barrett's esophagus. One patient presented with multiple sessile or pedunculated polyps giving a polyposis appearance; the other two patients had single polyps associated with distinct adenocarcinoma arising in Barrett's esophagus. Polyps consisted of adenomatous proliferation with adenocarcinoma in the 3 patients. Review of the literature identified twelve previously reported cases. These cases show that although rare, adenomas may arise in Barrett's esophagus, and are most likely premalignant lesions such as other adenomas of the gastrointestinal tract.

Adenocarcinoma of the esophagus is a well-known complication of Barrett's esophagus. This report describes five patients (three men and two women) with Barrett's esophagus and squamous carcinoma of the esophagus. All patients had hiatal hernia, and three had a history of tobacco and alcohol use. The tumors were located in the Barrett's mucosa in one case, at the squamocolumnar junction in two cases, and in the squamous-lined mucosa above the Barrett's mucosa in two cases. One patient also had focal adenocarcinoma associated with the squamous carcinoma of the esophagus. Review of the literature identified 11 previously reported cases. Occurrence of esophageal squamous carcinoma in Barrett's esophagus patients suggests a possible relationship between these two conditions, and the need for a careful evaluation of the squamous esophageal mucosa and the squamocolumnar junction at the time of endoscopy.