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Tumor Budding is an Independent Predictor of Outcome in AJCC/UICC Stage II Colorectal Cancer

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

In colorectal cancer, the morphology of the invasive tumor margin may reflect aggressiveness of tumor growth, thus providing important prognostic information. The tumor growth pattern according to Jass and the extent of tumor budding were analyzed in patients with American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) stage II disease.

Methods

Tumors of 120 randomly selected patients with AJCC/UICC stage II disease were retrospectively reviewed for tumor growth pattern (expanding vs. infiltrating) and the extent of tumor budding, with high-grade budding reflecting presence of 10 or more budding foci scattered at the invasive tumor margin. Progression-free and cancer-specific survivals were determined by the Kaplan–Meier method. For multivariable analysis, Cox’s proportional hazards regression models were performed.

Results

The infiltrating growth pattern was significantly associated with histological subtype and lymphovascular invasion, while high-grade budding was significantly associated with tumor grade and lymphovascular invasion. High-grade budding, but not the infiltrating growth pattern, was significantly associated with outcome in univariable analysis. Cox’s proportional hazards regression models proved tumor budding to be an independent predictor of disease progression (hazard ratio 3.91, 95 % confidence interval 1.3–11.77; P = 0.02) and cancer-related death (hazard ratio 5.90, 95 % confidence interval 1.62–21.51; P = 0.007). The combination of infiltrating growth pattern and high-grade budding did not have a stronger prognostic significance than tumor budding alone.

Conclusions

Tumor budding independently predicted patient outcome in patients with AJCC/UICC stage II colorectal cancer and may therefore be used for accurate prognostication, patient counseling, and design of clinical trials by using integrated multimodal therapy.

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References

  1. Compton CC. Optimal pathologic staging: defining stage II disease. Clin Cancer Res. 2007;13:6862–70.

    Article  Google Scholar 

  2. McLeod HL, Murray GI. Tumour markers of prognosis in colorectal cancer. Br J Cancer. 1999;79:191–203.

    Article  CAS  PubMed  Google Scholar 

  3. Lyall MS, Dundas SR, Curran S, Murray GI. Profiling markers of prognosis in colorectal cancer. Clin Cancer Res. 2006;12:1184–91.

    Article  CAS  PubMed  Google Scholar 

  4. Jass JR, Atkin WS, Cuzick J, et al. The grading of rectal cancer: historical perspectives and a multivariate analysis of 447 cases. Histopathology. 1986;10:437–59.

    Article  CAS  PubMed  Google Scholar 

  5. Jass JR, Love SB, Northover JM. A new prognostic classification of rectal cancer. Lancet. 1987;1:1303–6.

    Article  CAS  PubMed  Google Scholar 

  6. 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  CAS  PubMed  Google Scholar 

  7. 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  CAS  PubMed  Google Scholar 

  8. Prall F. Tumour budding in colorectal carcinoma. Histopathology. 2007;50:151–62.

    Article  CAS  PubMed  Google Scholar 

  9. Moertel CG, Fleming TR, Macdonald JS, et al. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990;322:352–8.

    Article  CAS  PubMed  Google Scholar 

  10. Sobin L, Gospodarowicz MK, Wittekind C. TNM classification of malignant tumors. 7th edition. West Sussex: Wiley-Blackwell; 2010.

    Google Scholar 

  11. Hamilton SR, Bosman FT, Boffetta P, et al. Carcinoma of the colon and rectum. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. World Health Organization classification of tumours of the digestive system. Lyon: IARC; 2010. p. 131–81.

    Google Scholar 

  12. Kanazawa H, Mitomi H, Nishiyama Y, et al. Tumour budding at invasive margins and outcome in colorectal cancer. Colorectal Dis. 2008;10:41–7.

    CAS  PubMed  Google Scholar 

  13. Zlobec I, Terracciano L, Tornillo L, et al. Role of RHAMM within the hierarchy of well-established prognostic factors in colorectal cancer. Gut. 2008;57:1413–9.

    Article  CAS  PubMed  Google Scholar 

  14. Ueno H, Price AB, Wilkinson KH, Jass JR, Mochizuki H, Talbot IC. A new prognostic staging system for rectal cancer. Ann Surg. 2004;240:832–9.

    Article  PubMed  Google Scholar 

  15. 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 

  16. Choi DH, Sohn DK, Chang HJ, Lim SB, Choi HS, Jeong SY. Indications for subsequent surgery after endoscopic resection of submucosally invasive colorectal carcinomas: a prospective cohort study. Dis Colon Rectum. 2009;52:438–45.

    Article  PubMed  Google Scholar 

  17. Ohtsuki K, Koyama F, Tamura T, et al. Prognostic value of immunohistochemical analysis of tumor budding in colorectal carcinoma. Anticancer Res. 2008;28:1831–6.

    PubMed  Google Scholar 

  18. Shepherd NA, Saraga EP, Love SB, Jass JR. Prognostic factors in colonic cancer. Histopathology. 1989;14:613–20.

    Article  CAS  PubMed  Google Scholar 

  19. Cianchi F, Messerini L, Palomba A, et al. Character of the invasive margin in colorectal cancer: does it improve prognostic information of Dukes staging? Dis Colon Rectum. 1997;40:1170–6.

    Article  CAS  PubMed  Google Scholar 

  20. Roncucci L, Fante R, Losi L, et al. Survival for colon and rectal cancer in a population-based cancer registry. Eur J Cancer. 1996;32A:295–302.

    Article  CAS  PubMed  Google Scholar 

  21. Ueno H, Jones A, Jass JR, Talbot IC. Clinicopathological significance of the “keloid-like” collagen and myxoid stroma in advanced rectal cancer. Histopathology. 2002;40:327–34.

    Article  CAS  PubMed  Google Scholar 

  22. Cianchi F, Messerini L, Comin CE, et al. Pathologic determinants of survival after resection of T3N0 (stage IIA) colorectal cancer: proposal for a new prognostic model. Dis Colon Rectum. 2007;50:1332–41.

    Article  PubMed  Google Scholar 

  23. Zlobec I, Baker K, Minoo P, Hayashi S, Terracciano L, Lugli A. Tumor border configuration added to TNM staging better stratifies stage II colorectal cancer patients into prognostic subgroups. Cancer. 2009;115:4021–9.

    Article  PubMed  Google Scholar 

  24. Nakamura T, Mitomi H, Kanazawa H, Ohkura Y, Watanabe M. Tumor budding as an index to identify high-risk patients with stage II colon cancer. Dis Colon Rectum. 2008;51:568–72.

    Article  PubMed  Google Scholar 

  25. 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 

  26. Wang LM, Kevans D, Mulcahy H, et al. Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer. Am J Surg Pathol. 2009;33:134–41.

    Article  CAS  PubMed  Google Scholar 

  27. Prall F, Nizze H, Barten M. Tumour budding as prognostic factor in stage I/II colorectal carcinoma. Histopathology. 2005;47:17–24.

    Article  CAS  PubMed  Google Scholar 

  28. Shinto E, Jass JR, Tsuda H, et al. Differential prognostic significance of morphologic invasive markers in colorectal cancer: tumor budding and cytoplasmic podia. Dis Colon Rectum. 2006;49:1422–30.

    Article  PubMed  Google Scholar 

  29. Yoshida K, Yoshimatsu K, Otani T, Yokomizo H, Ogawa K. The depth of tumor invasion beyond the outer border of the muscularis propria as a prognostic factor for T3 rectal/rectosigmoid cancer. Anticancer Res. 2008;28:1773–8.

    PubMed  Google Scholar 

  30. 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 

  31. De Quay N, Cerottini JP, Albe X, Saraga E, Givel JC, Caplin S. Prognosis in Duke’s B colorectal carcinoma: the Jass classification revisited. Eur J Surg. 1999;165:588–92.

    Article  PubMed  Google Scholar 

  32. Sato H, Maeda K, Sugihara K, et al. High-risk stage II colon cancer after curative resection. J Surg Oncol. 2011;104:45–52.

    Article  PubMed  Google Scholar 

  33. Vieth M, Quirke P, Lambert R, von Karsa L, Risio M. Annex to Quirke et al. Quality assurance in pathology in colorectal cancer screening and diagnosis: annotations of colorectal lesions. Virchows Arch. 2011;458:21–30.

    Article  PubMed  Google Scholar 

  34. Compton CC. Colorectal carcinoma: diagnostic, prognostic, and molecular features. Mod Pathol. 2003;16:376–88.

    Article  PubMed  Google Scholar 

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Conflict of interest

No conflict of interest and no financial disclosures from any author.

Author information

Authors and Affiliations

  1. Institute of Pathology, Medical University of Graz, Graz, Austria

    Johannes Betge MD, Marion J. Pollheimer MD, Richard A. Lindtner MD & Cord Langner MD

  2. Division of General Surgery, Department of Surgery, Medical University of Graz, Graz, Austria

    Peter Kornprat MD

  3. Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria

    Andrea Schlemmer

  4. Research Unit for Biomedical Engineering and Computing, Department of Surgery, Medical University of Graz, Graz, Austria

    Peter Rehak PhD

  5. Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany

    Michael Vieth MD

Authors
  1. Johannes Betge MD
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  2. Peter Kornprat MD
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  3. Marion J. Pollheimer MD
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  4. Richard A. Lindtner MD
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  5. Andrea Schlemmer
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  6. Peter Rehak PhD
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  7. Michael Vieth MD
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  8. Cord Langner MD
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Corresponding author

Correspondence to Cord Langner MD.

Additional information

Johannes Betge and Peter Kornprat contributed equally to this study.

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Betge, J., Kornprat, P., Pollheimer, M.J. et al. Tumor Budding is an Independent Predictor of Outcome in AJCC/UICC Stage II Colorectal Cancer. Ann Surg Oncol 19, 3706–3712 (2012). https://doi.org/10.1245/s10434-012-2426-z

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  • DOI: https://doi.org/10.1245/s10434-012-2426-z

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