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Molecular Bases of Human Stomach Carcinogenesis

  • Chapter
Molecular Pathology of Gastroenterological Cancer

Summary

Multiple genetic alterations, including inactivation of tumor-suppressor genes, activation of oncogenes, and reactivation of telomerase, are implicated in human stomach carcinogenesis. Among them, replication errors (RERs) at microsatellite loci, reactivation of telomerase, activation of c-met, inactivation of p53, and deranged CD44 transcription are common events of both welldifferentiated and poorly differentiated gastric carcinomas. In addition to these common events, K-ras mutation, APC inactivation, loss of DCC, and amplification of c-erbB2 are preferentially found in well-differentiated gastric carcinomas, whereas gene mutations, loss of the cadherin/ catenin system, and amplification of K-sam are frequently observed in poorly differentiated cancers. In addition, a paracrine loop formed between cancer cells and stromal cells through the hepatocyte growth factor/c-met system plays an important role in morphogenesis and invasion of gastric carcinoma with different status of adhesion molecules and signal transduction systems in vivo. Reduction or loss of p27 protein, associated with overexpression of cyclin E, may confer the progression and metastasis. In regard to precancerous lesions of the stomach, some of the intestinal metaplasias and adenomas exhibited the same genetic alterations (e.g. mutations of APC and p53, RERs, and reactivation of telomerase) and telomere shortening as those found in well-differentiated carcinomas. Moreover, human telomerase RNA overexpression, which correlates well with the number of Helicobacter pylori present, may precede telomerase reactivation in human stomach carcinogenesis. These observations suggest overall that there are two distinct genetic pathways in human stomach carcinogenesis, and some well-differentiated cancers share the same multistep genetic alterations as those established for colorectal cancers.

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Authors and Affiliations

  1. First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan

    Hiroshi Yokozaki, Hiroki Kuniyasu, Shuho Semba, Wataru Yasui & Eiichi Tahara

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  1. Hiroshi Yokozaki
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  2. Hiroki Kuniyasu
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  3. Shuho Semba
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  4. Wataru Yasui
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  5. Eiichi Tahara
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Editors and Affiliations

  1. Faculty of Medicine, First Department of Pathology, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734, Japan

    Eiichi Tahara M.D., Ph.D. (Director, Professor and Chairman) (Director, Professor and Chairman)

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Yokozaki, H., Kuniyasu, H., Semba, S., Yasui, W., Tahara, E. (1997). Molecular Bases of Human Stomach Carcinogenesis. In: Tahara, E. (eds) Molecular Pathology of Gastroenterological Cancer. Springer, Tokyo. https://doi.org/10.1007/978-4-431-65915-0_6

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  • DOI: https://doi.org/10.1007/978-4-431-65915-0_6

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