Skip to main content
SpringerLink
Log in

Tumor Budding as an Index to Identify High-Risk Patients with Stage II Colon Cancer

  • Original Contribution
  • Published:
Diseases of the Colon & Rectum

Abstract

Purpose

High-risk patients with Stage II colon cancer may benefit from adjuvant chemotherapy, but they are difficult to identify. We assessed the value of tumor budding, defined as small clusters of undifferentiated cancer cells at invasive margins, as a predictor of outcomes in patients with Stage II colon cancer.

Methods

We studied a total of 200 patients with Stage II colon cancer who underwent curative surgery. With hematoxylin and eosin-stained specimens, the degree of tumor budding was classified as low-grade or high-grade. The survival rate of patients who had Stage II disease with low-grade or high-grade tumor budding was compared with that of 226 patients who had Stage III colon cancer.

Results

Univariate analysis revealed that serosal surface involvement (P = 0.04) and tumor budding (P < 0.001) were significantly related to survival. Cumulative five- and ten-year survival rates differed significantly between patients with low-grade tumor budding (93.9 and 90.6 percent, respectively) and those with high-grade (73.9 and 67.8 percent, respectively). Survival rates did not differ significantly between patients with Stage II disease who had high-grade tumor budding and patients with Stage III disease. Cox’s regression analysis demonstrated that tumor budding (hazard ratio, 4.89; P < 0.001) and serosal surface involvement (hazard ratio, 2.561; P = 0.023) were independent prognostic factors. Liver (P < 0.001) and peritoneal (P = 0.003) metastases were more frequent in the patients with high-grade tumor budding than in those with low-grade.

Conclusions

Tumor budding is useful for prognosis and identifying patients with Stage II colon cancer who have a high risk of disease recurrence after curative surgery.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Sobin LH, Wittekind Ch. International Union Against Cancer (UICC). TNM classification of malignant tumours. 6th ed. New York: Wiley-Liss, Inc., 2002.

    Google Scholar 

  2. Macdonald JS, Astrow AB. Adjuvant therapy of colon cancer. Semin Oncol 2001;28:30–40.

    Article  PubMed  CAS  Google Scholar 

  3. Merkel S, Wein A, Günther K, Papadopoulos T, Hohenberger W, Hermanek P. High-risk groups of patients with Stage II colon carcinoma. Cancer 2001;92:1435–43.

    Article  PubMed  CAS  Google Scholar 

  4. Burdy G, Panis Y, Alves A, Nemeth J, Lavergne-Slove A, Valleur P. Identifying patients with T3-T4 node-negative colon cancer at high risk of recurrence. Dis Colon Rectum 2001;44:1682–8.

    Article  PubMed  CAS  Google Scholar 

  5. Chapuis PH, Dent OF, Bokey EL, Newland RC, Sinclair G. Adverse histopathological findings as a guide to patient management after curative resection of node-positive colonic cancer. Br J Surg 2004;91:349–54.

    Article  PubMed  CAS  Google Scholar 

  6. Porschen R, Bermann A, Löffler T, Haack G, Rettig K, Anger Y, Strohmeyer G. Fluorouracil plus leucovorin as effective adjuvant chemotherapy in curatively resected Stage III colon cancer: results of the trial adjCCA-01. J Clin Oncol 2001;19:1787–94.

    PubMed  CAS  Google Scholar 

  7. Tanaka M, Hashiguchi Y, Ueno H, Hase K, Mochizuki H. Tumor budding at the invasive margin can predict patients at high risk of recurrence after curative surgery for Stage II, T3 colon cancer. Dis Colon Rectum 2003;46:1054–9.

    Article  PubMed  Google Scholar 

  8. Okuyama T, Nakamura T, Yamaguchi M. Budding is useful to select high-risk patients in Stage II well-differentiated or moderately differentiated colon adenocarcinoma. Dis Colon Rectum 2003;46:1400–6.

    Article  PubMed  Google Scholar 

  9. Okuyama T, Oya M, Ishikawa H. Budding as a useful prognostic marker in pT3 well- or moderately differentiated rectal adenocarcinoma. J Surg Oncol 2003;83:42–7.

    Article  PubMed  Google Scholar 

  10. Ueno H, Murphy J, Jass JR, Mochizuki H, Talbot IC. Tumour ‘budding’ as an index to estimate the potential of aggressiveness in rectal cancer. Histopathology 2002;40:127–32.

    Article  PubMed  CAS  Google Scholar 

  11. Okuyama T, Oya M, Yamaguchi M. Budding (sprouting) as a useful prognostic marker in colorectal mucinous carcinoma. Jpn J Clin Oncol 2002;32:412–6.

    Article  PubMed  Google Scholar 

  12. Park K-J, Choi H-J, Roh M-S, Kwon H-C, Kim C. Intensity of tumor budding and its prognostic implications in invasive colon carcinoma. Dis Colon Rectum 2005;48:1597–602.

    Article  PubMed  Google Scholar 

  13. Morodomi T, Isomoto H, Shirouzu K, Kakegawa K, Irie K, Morimatsu M. An index for estimating the probability of lymph node metastasis in rectal cancers: lymph node metastasis and the histopathology of actively invasive regions of cancer. Cancer 1989;63:539–43.

    Article  PubMed  CAS  Google Scholar 

  14. Hase K, Shatney C, Johnson D, Trollope M, Vierra M. Prognostic value of tumor “budding” in patients with colorectal cancer. Dis Colon Rectum 1993;36:627–35.

    Article  PubMed  CAS  Google Scholar 

  15. Mitomi H, Mori A, Kanazawa H, et al. Venous invasion and down-regulation of p21WAF1/CIP1 are associated with metastasis in colorectal carcinomas. Hepato-Gastroenterology 2005;52:1421–6.

    PubMed  Google Scholar 

  16. Okuyama T, Oya M, Ishikawa H. Budding as a risk factor for lymph node metastasis in pT1 or pT2 well-differentiated colorectal adenocarcinoma. Dis Colon Rectum 2002;45:628–34.

    Article  PubMed  Google Scholar 

  17. Nakamura T, Mitomi H, Kikuchi S, Ohtani Y, Sato K. Evaluation of the usefulness of tumor budding on the prediction of metastasis to the lung and liver after curative excision of colorectal cancer. Hepato-Gastroenterology 2005;52:1432–5.

    PubMed  Google Scholar 

  18. Gabbert H, Wagner R, Moll R, Gerharz C-D. Tumor dedifferentiation: an important step in tumor invasion. Clin Expl Metastasis 1985;3:257–79.

    Article  CAS  Google Scholar 

  19. Masaki T, Matsuoka H, Sugiyama M, et al. Laminin-5 γ 2 chain expression as a possible determinant of tumor aggressiveness in T1 colorectal carcinomas. Dig Dis Sci 2003;48:272–8.

    Article  PubMed  Google Scholar 

  20. Masaki T, Sugiyama M, Matsuoka H, et al. Coexpression of matrilysin and laminin-5 γ2 chain may contribute to tumor cell migration in colorectal carcinomas. Dig Dis Sci 2003;48:1262–7.

    Article  PubMed  CAS  Google Scholar 

  21. Guziñska-Ustymowicz K, Zalewski B, Kasacka I, Piotrowski Z, Skrzydlewska E. Activity of cathepsin B and D in colorectal cancer: relationships with tumour budding. Anticancer Res 2004;24:2847–52.

    PubMed  Google Scholar 

  22. Jass JR, Baker M, Fraser L, et al. APC mutation and tumour budding in colorectal cancer. J Clin Pathol 2003;56:69–73.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank M. Yokozawa and I. Yokoyama, Department of Pathology, Kitasato University East Hospital, for their expert technical assistance.

Author information

Authors and Affiliations

  1. Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan

    Takatoshi Nakamura M.D. & Masahiko Watanabe M.D.

  2. Department of Clinical Research Laboratory, National Hospital Organization, Sagamihara Hospital, Sagamihara, Kanagawa, Japan

    Hiroyuki Mitomi M.D.

  3. Department of Surgery, National Hospital Organization, Sagamihara Hospital, Sagamihara, Kanagawa, Japan

    Hideki Kanazawa M.D.

  4. Department of Pathology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan

    Yasuo Ohkura M.D.

  5. Department of Surgery, Kitasato University, 1-15-1 Kitasato, Sagamihara, Kanagawa, 228-8520, Japan

    Takatoshi Nakamura M.D.

Authors
  1. Takatoshi Nakamura M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroyuki Mitomi M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hideki Kanazawa M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yasuo Ohkura M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Masahiko Watanabe M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Takatoshi Nakamura M.D..

About this article

Cite this article

Nakamura, T., Mitomi, H., Kanazawa, H. et al. Tumor Budding as an Index to Identify High-Risk Patients with Stage II Colon Cancer. Dis Colon Rectum 51, 568–572 (2008). https://doi.org/10.1007/s10350-008-9192-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10350-008-9192-9

Key words

Search

Navigation