Junzo Kudo

Survivin, a new member of the inhibitor-of-apoptosis (IAP) family, has been reported to be expressed in many cancers but not in differentiated normal tissue. Its expression in esophageal cancer, however, has not been reported. We investigated 51 esophageal cancers and their adjacent normal epithelial tissues for mRNA expression of survivin by RT-PCR. The survivin expression in esophageal cancer tissue was significantly higher than that in normal esophageal tissue (0.211 +/- 0.226 vs. 0.057 +/- 0.135, p < 0.0001). pN4 tumors had significantly higher survivin expression than the pN0-3 tumors (p = 0.0093). Fourteen patients with advanced esophageal cancer had received chemotherapy prior to surgery. The survivin expression in the cancer tissue in patients who achieved a partial response (PR) was significantly lower than that in patients with no change (NC) and in patients with progressive disease (PD; 0.099 +/- 0.134 vs. 0.320 +/- 0.222, p = 0.0434). The median survival for patients with high survivin expression (9.0 months) was less than that for patients with low survivin group expression (30.0 months, p = 0.0023). Survivin expression was one of the significant predictors of survival on univariate analysis (hazard ratio 2.471; 95% confidence interval 1.104-5.533). The results suggest that survivin expression may provide prognostic information in patients with esophageal cancer.

BACKGROUND: beta-catenin is a multifunctional protein involved in two apparently independent processes: cell-cell adhesion and signal transduction. beta-catenin is involved in Wnt signaling pathway that regulates cellular differentiation and proliferation. In this study, we investigated the expression pattern of beta-catenin and cyclin D1 using immunohistochemistry and searched for mutations in exon 3 of the beta-catenin gene and Axin gene in esophageal squamous cell carcinoma. MATERIALS AND METHODS: Samples were obtained from 50 esophageal cancer patients. Immunohistochemical staining for beta-catenin and cyclin D1 was done. Mutational analyses of the exon3 of the beta-catenin gene and Axin gene were performed on tumors with nuclear beta-catenin expression. RESULTS: Four (8%) esophageal cancer tissues showed high nuclear beta-catenin staining. Overexpression of cyclin D1 was observed in 27 out of 50 (54%) patients. All four cases that showed nuclear beta-catenin staining overexpressed cyclin D1. No relationship was observed between the expression pattern of beta-catenin and cyclin D1 and age, sex, tumor size, stage, differentiation grade, lymph node metastasis, response to chemotherapy, or survival. No mutational change was found in beta-catenin exon 3 in the four cases with nuclear beta-catenin staining. Sequencing analysis of the Axin cDNA revealed only a splicing variant (108 bp deletion, position 2302-2409) which was present in the paired normal mucosa. CONCLUSION: A fraction of esophageal squamous cell carcinomas have abnormal nuclear accumulation of beta-catenin accompanied with increased cyclin D1 expression. Mutations in beta-catenin or axin genes are not responsible for this abnormal localization of beta-catenin.

Survivin, a new member of the inhibitor-of-apoptosis (IAP) family, has been reported to be expressed in many cancers but not in differentiated normal tissue. Its expression in esophageal cancer, however, has not been reported. We investigated 51 esophageal cancers and their adjacent normal epithelial tissues for mRNA expression of survivin by RT-PCR. The survivin expression in esophageal cancer tissue was significantly higher than that in normal esophageal tissue (0.211 ± 0.226 vs. 0.057 ± 0.135, p < 0.0001). pN4 tumors had significantly higher survivin expression than the pN0-3 tumors (p = 0.0093). Fourteen patients with advanced esophageal cancer had received chemotherapy prior to surgery. The survivin expression in the cancer tissue in patients who achieved a partial response (PR) was significantly lower than that in patients with no change (NC) and in patients with progressive disease (PD; 0.099 ± 0.134 vs. 0.320 ± 0.222, p = 0.0434). The median survival for patients with high survivin expression (9.0 months) was less than that for patients with low survivin group expression (30.0 months, p = 0.0023). Survivin expression was one of the significant predictors of survival on univariate analysis (hazard ratio 2.471; 95% confidence interval 1.104-5.533). The results suggest that survivin expression may provide prognostic information in patients with esophageal cancer. © 2001 Wiley-Liss, Inc.

BACKGROUND: DNA fragmentation factor 45 (DFF45)/inhibotor of caspase activated DNAse (ICAD) forms a complex with DFF40/CAD and inhibits its DNA cleaving function during apoptosis. DFF45 also functions as a chaperone for native DFF40 and is necessary for its function. It has been indicated that defects in the apoptotic pathway may exist in neoplastic cells. METHODS: The authors investigated mRNA expression of DFF45 in a series of 46 esophageal squamous cell carcinoma (ESCC) specimens using polymerase chain reaction amplification. The results were correlated with the patients' clinicopathologic characteristics. RESULTS: DFF45 mRNA expression was significantly lower in tumors with higher pathologic stage, higher tumor status (T status), lymph node metastasis, or more extensive lymphatic invasion. Patients who had low DFF45 mRNA expression (indicated by the ratio of DFF45 mRNA expression in tumor to DFF45 mRNA expression in normal esophageal mucosa [tumor:normal] < 1) had a significantly shorter survival after undergoing surgery compared with patients who had high DFF45 mRNA expression (tumor:normal > 1, P = 0.0006; log-rank test, P = 0.0003; median follow-up, 14.6 months). CONCLUSIONS: Patients with ESCC with decreased DFF45 mRNA expression levels had a poor prognosis compared with patients who had high DFF45 mRNA expression levels.

A 29-year-old male who had a 15-year history of alcohol drinking was admitted with a 5-month history of jaundice in July 1989. Laboratory examinations revealed that he had hemolytic anemia and severe liver damage. Erythrocytes of peripheral blood showed typical spiculated cells on light microscopic and scanning electron microscopic studies. Free-cholesterol/phospholipid ratio of the erythrocyte membrane was elevated, and the level of chenodeoxycholic acid increased in serum. The patient was diagnosed as having advanced alcoholic cirrhosis associated with spur cell anemia. Two months after admission, he was complicated with chronic disseminated intravascular coagulopathy (DIC). Anemia, hepatic failure and DIC progressed, and the patient died six months after admission. The mechanism of the formation of spur cells was discussed.