Expression of CD44 in premalignant and malignant Barrett's oesophagus

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Abstract
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. 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. 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.