IDENTIFICATION OF CYSTATIN-B IN HUMAN ESOPHAGEAL-CARCINOMA, USING DIFFERENTIAL DISPLAYS IN WHICH THE GENE-EXPRESSION IS RELATED TO LYMPH-NODE METASTASIS

Identification of the genes that are specifically expressed in either tumor or normal tissue is important for understanding cancer biology. Using differential displays, we obtained one gene which was specifical ly expressed in normal tissue but is only rarely expressed in carcinom a tissue of the human esophagus, The sequence of this gene was identic al with cystatin B, known to be one of the cysteine-proteinase inhibit ors, mainly inhibiting cathepsin L, There is little information on the clinical significance of cystatin B expression in human esophageal ca rcinoma. We thus studied the mRNA expression of cystatin B in 45 tumor /normal pair specimens of the esophagus, using the semi-quantitative r everse transcriptase polymerase chain reaction technique. The expressi on of cystatin B in tumor tissue was found to be markedly decreased co mpared with that of the corresponding normal tissue. The cases with a tumor/normal ratio of less than 0.5 showed high frequency of lymph-nod e metastasis and more advanced clinical stage as compared with those w hose tumor/normal ratio was equal to or more than 0.5. The decreased e xpression of cystatin B protein in carcinoma tissue was confirmed by i mmunohistochemical staining. Our study suggests that reduced expressio n of cystatin B in esophageal-carcinoma tissue is associated with lymp h-node metastasis and may therefore prove to be a useful marker for pr edicting the biologic aggressiveness of human esophageal carcinoma. (C ) 1998 Wiley-Liss, Inc.