Multistep Carcinogenesis of Esophageal Carcinoma

  • Yusuke Nakamura
  • Takashi Tokino
  • Minoru Isomura
  • Johji Inazawa
  • Takahisa Aoki
  • Takahiro Mori
  • Mamoru Shimada
  • Koh Miura
  • Kazufumi Suzuki


To investigate genetic features of esophageal cancer, we have examined a large number of squamous cell carcinomas of the esophagus (ESCs) for loss of heterozygosity (LOH) using polymorphic DNA markers representing all autosomal chromosomes. Allelic losses at frequencies of at least 30% were observed at loci on chromosomal arms on 3p (33%), 3q (30%), 5q (36%), 9p (57%), 9q (60%), 10p (33%), 13q (43%), 17p (62%), 17q (46%), 18q (38%), 19q (32%), and 21q (37%). By comparing the LOH on each chromosomal arm with the clinicopathologic parameters of patients, we found a significant correlation between LOH on 19q and regional lymph node metastasis. Interestingly, the frequency of LOH on 17q was significantly higher in tumors from female patients (12 of 14 cases) than in those from male patients (20 of 56 cases) P =0.0009 by Fisher’s exact test). Subsequent analysis of allelic losses in DNA extracts isolated from 106 lesions among 32 patients with ESCs revealed that allelic losses on 3p or 17p occurred frequently even in dysplastic lesions, and that allelic losses on these chromosomal arms were observed in cancerous tissues as well. We detected allelic losses of the short and long arms of chromosome 9 at low frequency in lesions with mild dysplasia but often in lesions with severe dysplasia and in intraepithelial cancers. Our results suggested that inactivation of tumor suppressor genes on 3p and 17p occurs at an early stage of esophageal carcinogenesis, and that genes on 9p and 9q are likely to play important roles in malignant changes.


Esophageal Cancer Esophageal Squamous Cell Carcinoma Esophageal Carcinoma Allelic Loss Epithelial Growth Factor Receptor 
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Copyright information

© Springer Japan 1997

Authors and Affiliations

  • Yusuke Nakamura
    • 1
  • Takashi Tokino
    • 1
  • Minoru Isomura
    • 1
  • Johji Inazawa
    • 1
  • Takahisa Aoki
    • 1
  • Takahiro Mori
    • 1
  • Mamoru Shimada
    • 1
  • Koh Miura
    • 1
  • Kazufumi Suzuki
    • 1
  1. 1.Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical ScienceUniversity of TokyoMinato-ku, Tokyo 108Japan

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