We investigated the significances of the expressions of dihydrodiol dehydrogenase (DDH) and glutathione-S-transferase (GST) in patients with esophageal squamous cell carcinoma (ESCC). By using immunohistochemistry, we measured expressions of DDH, GST, COX-2, nm23-H1, HER-2/neu and mdr-1 in 145 patients with ESCC. Expression of DDH was confirmed by immunoblotting and reverse transcription-polymerase chain reaction. Relation between DDH expression and clinicopathological parameters was analyzed by statistical analysis. Difference of survivals between different groups was compared by a log rank test. DDH overexpression was detected in 66.9% of pathological sections (97/145) and in 41.6% of metastatic lymph nodes (37/89). The nucleotide sequencing of DNA fragments from 16 tumorous specimens showed that the major isoform was DDH2 for ESCC. GST expression, however, was only detected weakly in 24 patients (16.6%). For patients with ESCC, DDH overexpression was positively correlated with smoking habit, tumor stage, number of metastatic lymph nodes, lymphovascular invasion and COX-2 expression, and inversely correlated with GST and nm23-H1 expressions, but not related to mdr-1 or HER-2/neu expressions. As compared to DDH overexpressed group, patients with low DDH expression had significantly lower incidence of tumor recurrences and better survival (p = 0.026). Using univariate analysis, prognostic factors included tumor stage, number of metastatic lymph nodes, cell differentiation, lymphovascular invasion and expressions of DDH and nm23-H1. Multivariate analysis showed significant correlation of tumor stage, number of metastatic lymph nodes and nm23-H1 expression with patient's survival. In conclusion, inverse expressions of DDH and GST may be associated with carcinogenesis and disease progression for ESCC patients, but their biological function and pathophysiological regulation in tumors require additional studies.
Copyright 2004 Wiley-Liss, Inc.