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It has been reported that various cancers frequently have mutations in the D-loop region of mitochondrial DNA (mtDNA). We examined the genetic alterations in this region of esophageal cancer using direct sequencing. Of 68 sequence variants, 15 have not been reported to date. Tumor mtDNA with these variants were compared with mtDNA from corresponding normal esophageal mucosa. Two of 37 primary esophageal cancers (5%) contained somatic mutations in the D-loop region of mtDNA. Although the mutation rate of mitochondrial tumor DNA within the D-loop was not high, this result suggested that mtDNA mutations play a role in the development of esophageal cancer. © 2001 Wiley-Liss, Inc. Key words: mitochondria; mutation; esophageal cancerEsophageal cancer is one of the most aggressive cancers in the world. Accumulating evidence indicates that a series of genetic changes in dominant oncogenes such as cyclin D1 and hst1/int2 and tumor suppressor genes such as p53 and p16 are involved in the pathogenesis of human esophageal cancer. [1][2][3][4] Recently, it has been proved that genetic changes in mitochondrial DNA (mtDNA) cause a wide variety of diseases. 5 The mitochondrial genome is particularly susceptible to mutations because of the high level of reactive oxygen species (ROS) generation in this organelle, coupled with a low level of DNA repair. 6,7 Polyak et al. 8 found somatic mutations of mtDNA in 7 of 10 (70%) human colorectal cancer cell lines. Subsequently, somatic mitochondrial mutations were identified in various human cancers, and most mutations were found in the D-loop region of mtDNA. 9 Although the D-loop is the noncoding region of the mitochondrial genome, it contains essential transcription and replication elements. Therefore, mutations in the D-loop regulatory region might alter the rate of DNA replication by modifying the binding affinity of important trans-acting factors. This may be why various cancers frequently have mutations in the D-loop region. However, mtDNA alterations have not been reported in esophageal cancer until now.In the present study, we examined the genetic alterations in the D-loop region of mtDNA in esophageal cancer using direct sequencing. We found that 2/37 (5%) esophageal cancers had somatic mutations. Although the mutation rate of mitochondrial tumor DNA within the D-loop was not high, this result suggested that mtDNA mutations play a role in the development of esophageal cancer. MATERIAL AND METHODS Sample collection and DNA preparationThirty-seven primary tumors and corresponding normal tissues were collected at the Nagoya University School of Medicine from esophageal cancer patients who had been diagnosed histologically. All esophageal cancers were squamous cell carcinomas. These samples were obtained during surgery. All tissues were quickly frozen in liquid nitrogen and stored at Ϫ80°C until analysis. We stained frozen sections from the tumors by hematoxylin and eosin (H&E) staining and confirmed that more than 70% of the cells from resected tumor tissues were derived from tumo...

PurposeThe second planned interim analysis (median follow-up 12.5 months) in a phase III trial of postoperative adjuvant chemotherapy for stage III gastric cancer revealed significant improvement in relapse-free survival (RFS) for S-1 plus docetaxel over S-1 alone. Although enrollment was terminated on the recommendation of the independent data and safety monitoring committee, we continued follow-up and herein report on 3-year RFS, the primary endpoint. Patients and methods Patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. In the S-1 plus docetaxel group, S-1 was given orally for 2 weeks followed by 1 week of rest for seven courses, and docetaxel was given intravenously on day 1 of the second to seventh courses. The combination therapy was followed by S-1 monotherapy for up to 1 year. ResultsThe 3-year RFS rate of the S-1 plus docetaxel group was 67.7%. This was significantly superior to that of 57.4% in the S-1 group (hazard ratio [HR] 0.715, 95% CI 0.587-0.871, P = 0.0008). This translated into a significant benefit in the 3-year overall survival (OS) rate in the S-1 plus docetaxel group (77.7% versus 71.2%, HR 0.742, 95% CI 0.596-0.925, P = 0.0076). Conclusion On 3-year follow-up data, postoperative adjuvant therapy with S-1 plus docetaxel was confirmed to improve both RFS and OS and can be recommended as a standard of care for patients with stage III gastric cancer treated by D2 dissection.