AMPLIFICATION AND OVEREXPRESSION OF CYCLIN D1 IN AGGRESSIVE HUMAN ESOPHAGEAL CANCER

Cyclin D1 is a cell-cycle regulator essential for G1 phase progression and a candidate proto-oncogene implicated in pathogenesis of several human tumor types including esophageal cancers. Association between cy clin D1 gene amplification and clinical outcome was examined using Sou thern blotting in 45 patients with primary esophageal cancer. In cases showing gene amplification, expression levels of mRNA and gene produc t were further examined by Northern blotting, Western blotting and imm unohistochemical analyses. Amplification of cyclin D1 gene was found i n 14 of 45 patients (31.1%). There was no association between gene amp lification and clinicopathological parameters but the frequency of hem atogpenous recurrence in cases with gene amplification was significant ly higher than that in cases without amplification in 30 patients unde rgoing curative surgery (70.0% vs 25.0%, p<0.05). Furthermore, cumulat ive survival rate of cases with gene amplification was significantly l ower than that of cases without amplification (p<0.05). Overexpression of cyclin D1 mRNA was observed in 12 of 14 cases (85.7%) showing gene amplification but overexpression of its protein was found in only fou r cases (28.6%). Amplification of the cyclin D1 gene is a reliable pro gnostic factor and post-translational modification of this gene may pl ay a functionally important role in development of primary esophageal cancer.