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Relationship of BRAF mutation, morphology, and apoptosis in early colorectal cancer

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aims

Many investigators have reported flat and depressed lesions as a new type of precursor of colorectal cancer. In our previous study, we determined that mutations in the BRAF gene may contribute to colorectal carcinogenesis by inhibiting apoptosis. However, the relationship among BRAF mutations, morphology and apoptosis in early colorectal cancer has not been clear. Therefore, gene alternation, morphology, and apoptosis in early colorectal cancer were investigated.

Materials and methods

Forty-five flat and depressed early colorectal cancer samples and 43 polypoid early colorectal cancer samples were analyzed. Mutations in the BRAF gene and the K-ras gene were examined by direct sequence analysis, and proliferative activity and induction of apoptosis were evaluated using immunohistochemical examination.

Results findings

BRAF mutations were found in 5 (11.1%) of 45 flat and depressed early colorectal cancer samples. No BRAF alteration was found in polypoid early colorectal cancer samples. Mutations in the K-ras gene were detected in 13 (30.2%) of 43 polypoid early colorectal cancer samples. The rate of submucosal invasion of the samples with BRAF mutations was significantly higher than that of the samples with K-ras mutations (p < 0.05).

Interpretation/conclusions

BRAF and K-ras mutations were independent factors that influenced morphology in early colorectal cancer. In this study, the relationship between BRAF mutation and apoptosis is not so clear, but BRAF mutations and inhibition in apoptosis may play an important role in the developmental process of flat and depressed early colorectal cancer.

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Abbreviations

PCR:

polymerase chain reaction

ssDNA:

single-stranded DNA

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Acknowledgments

The authors express great thanks to Miss Satomi Shigeta, Dr. Souzana Deenitchina, the staff of the Department of Endoscopy, the Division of Surgical Pathology, Department of Biomedical Informatics, Kobe University Graduate School of Medicine.

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Authors and Affiliations

  1. Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan

    Shiei Yoshida, Nobunao Ikehara, Daisuke Shirasaka, Tadateru Hasuo, Ikuya Miki, Takao Tamura & Masato Kasuga

  2. Division of Surgical Pathology, Department of Biomedical Informatics, Kobe University Graduate School of Medicine, Kobe, Japan

    Nobunao Ikehara, Shuho Semba, Tadateru Hasuo & Hiroshi Yokozaki

  3. Department of Endoscopy, Kobe University Graduate School of Medicine, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Nobuo Aoyama

  4. Department of Gastroenterology, Kobe Red Cross Hospital, Kobe, Japan

    Masanori Sakashita

  5. Department of Frontier Medical Science in Gastroenterology, International Center for Medical Research and Treatment, Kobe University Graduate School of Medicine, Kobe, Japan

    Yoshinori Morita & Takeshi Azuma

Authors
  1. Shiei Yoshida
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  2. Nobunao Ikehara
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  3. Nobuo Aoyama
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  4. Daisuke Shirasaka
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  5. Masanori Sakashita
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  6. Shuho Semba
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  7. Tadateru Hasuo
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  8. Ikuya Miki
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  9. Yoshinori Morita
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  10. Takao Tamura
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  11. Takeshi Azuma
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  12. Hiroshi Yokozaki
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  13. Masato Kasuga
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Corresponding author

Correspondence to Nobuo Aoyama.

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Yoshida, S., Ikehara, N., Aoyama, N. et al. Relationship of BRAF mutation, morphology, and apoptosis in early colorectal cancer. Int J Colorectal Dis 23, 7–13 (2008). https://doi.org/10.1007/s00384-007-0349-0

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  • DOI: https://doi.org/10.1007/s00384-007-0349-0

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