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Tumor budding as a prognostic marker in stage-III rectal carcinoma

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Background and aim

Tumor budding along the invasive margin is known to be associated with biological behavior in colorectal carcinoma. The aims of this study were to explore if the semiquantitative assessment of tumor budding in rectal cancers correlates with oncological behavior and to appraise if the tumor budding is valid as a pathological parameter in distinguishing tumors with higher malignancy potential from those with lower one for prognostic stratification.

Materials and methods

Surgical specimens from 244 patients with well- or moderately differentiated rectal carcinoma were retrieved to assess the intensity of tumor budding at the invasive margin. Intensities were divided semiquantitatively into four groups based on quartiles, and the 5-year disease-free survivals (DFS) were analyzed to search for a cutoff point of prognostic stratification.

Results

The cutoff of the intensity considered to be the best indicator for dividing patients into subgroups with different DFS was between quartiles 3 and 4, but this survival difference in subgroups in either side of the cutoff was significant only in stage-III disease [5-year DFS, 62.1 vs 35.1%; p = 0.0023; 95% confidence interval (CI), 0.1824–0.6919]. Based on multivariate analysis, the intensity of budding proved to be an independent variable associated with DFS (hazard ratio, 2.005; p = 0.0086; 95% CI, 1.021–3.934). When scores were given to grade of budding (lower, 0; higher, 1) and N stage (N1, 0; N2, 1) in stage III, a better prognostic stratification in terms of the 5-year DFS was obtained than the American Joint Committee on Cancer nodal staging only (0 vs 1 vs 2, 66.5 vs 42.6 vs 29.2%; p = 0.0101).

Conclusions

Quantitative assessment of tumor budding is a reliable biological prognostic variable to identify higher malignancy potential. Scoring system using tumor budding and N stage showed better prognostic stratification in stage-III rectal carcinoma. A prospective evaluation would confirm the clinical significance of tumor budding for prognostic stratification.

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References

  1. Jass JR, Morson BC (1987) Reporting colorectal cancer. Br J Clin Pathol 40:1016–1023

    Article  CAS  Google Scholar 

  2. Fielding LP, Phillips RK, Fry JS, Hittinger R (1986) Prediction of outcome after curative resection for large bowel cancer. Lancet 18:904–907

    Article  Google Scholar 

  3. Michelassi F, Ayala JJ, Balestracci T, Goldberg R, Chappell R, Block GE (1991) Verification of a new clinicopathologic staging system for colorectal adenocarcinoma. Ann Surg 214:11–18

    PubMed  CAS  Google Scholar 

  4. Harrison JC, Dean PJ, El-Zeky F, Vander Zwaag R (1994) From Dukes through Jass: pathological prognostic indicators in rectal cancer. Hum Pathol 25:498–505

    Article  PubMed  CAS  Google Scholar 

  5. Morodomi T, Isomoto H, Shirouzu K, Kakegawa K, Irie K, Morimatsu M (1989) 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 63:539–543

    Article  PubMed  CAS  Google Scholar 

  6. Hase K, Shatney C, Johnson D, Trollope M, Vierra M (1993) Prognostic value of tumor “budding” in patients with colorectal cancer. Dis Colon Rectum 36:627–635

    Article  PubMed  CAS  Google Scholar 

  7. Gabbert H (1985) Mechanism of tumor invasion: evidence from in vivo observations. Cancer Metastasis Rev 4:293–309

    Article  PubMed  CAS  Google Scholar 

  8. Okuyama T, Oya M, Ishikawa H (2003) Budding as a useful prognostic marker in pT3 well- or moderately-differentiated rectal adenocarcinoma. J Surg Oncol 83:42–47

    Article  PubMed  Google Scholar 

  9. Ueno H, Murphy J, Jass JR, Mochizuki H, Talbot IC (2002) Tumour ‘budding’ as an index to estimate the potential of aggressiveness in rectal cancer. Histopathology 40:127–132

    Article  PubMed  CAS  Google Scholar 

  10. Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170

    PubMed  CAS  Google Scholar 

  11. Cox DR (1972) Regression models and life tables. J R Stat Soc 34:187–220

    Google Scholar 

  12. Nowell PC (1986) Mechanisms of tumor progression. Cancer Res 46:2203–2207

    PubMed  CAS  Google Scholar 

  13. Frost P, Levin B (1992) Clinical implications of metastatic process. Lancet 339:1458–1461

    Article  PubMed  CAS  Google Scholar 

  14. Gabbert H (1985) Mechanism of tumor invasion: evidence from in vivo observations. Cancer Metastasis Rev 4:293–309

    Article  PubMed  CAS  Google Scholar 

  15. Sordat I, Rousselle P, Chaubert P, Petermann O, Aberdam D, Bosman FT, Sordat B (2000) Tumor cell budding and laminin-5 expression in colorectal carcinoma can be modulated by the tissue micro-environment. Int J Cancer 88:708–717

    Article  PubMed  CAS  Google Scholar 

  16. Pyke C, Salo S, Ralfkiaer E, Romer J, Dano K, Tryggvason K (1995) Laminin-5 is a marker of invading cancer cells in some human carcinomas and is coexpressed with the receptor for urokinase plasminogen activator in budding cancer cells in colon adenocarcinomas. Cancer Res 55:4132–4139

    PubMed  CAS  Google Scholar 

  17. Masaki T, Goto A, Sugiyama M, Matsuoka H, Abe N, Sakamoto A, Atomi Y (2001) Possible contribution of CD44 variant 6 and nuclear beta-catenin expression to the formation of budding tumor cells in patients with T1 colorectal carcinoma. Cancer 92:2539–2546

    Article  PubMed  CAS  Google Scholar 

  18. Fujiya M, Watari J, Ashida T, Honda M, Tanabe H, Fujiki T, Saitoh Y, Kohgo Y (2001) Reduced expression of syndecan-1 affects metastatic potential and clinical outcome in patients with colorectal cancer. Jpn J Cancer Res 92:1074–1081

    PubMed  CAS  Google Scholar 

  19. Ueno H, Mochizuki H, Shinto E, Hashiguchi Y, Hase K, Talbot IC (2002) Histologic indices in biopsy specimens for estimating the probability of extended local spread in patients with rectal carcinoma. Cancer 94:2882–2891

    Article  PubMed  Google Scholar 

  20. Ueno H, Mochizuki H, Hatsuse K, Hase K, Yamamoto T (2000) Indicators for treatment strategies of colorectal liver metastases. Ann Surg 231:59–66

    Article  PubMed  CAS  Google Scholar 

  21. Park KJ, Choi HJ, Roh MS, Kwon HC, Kim C (2005) Intensity of tumor budding and its prognostic implications in invasive colon carcinoma. Dis Colon Rectum 48:1597–1602

    Article  PubMed  Google Scholar 

  22. Ueno H, Price AB, Wilkinson KH, Jass JR, Mochizuki H, Talbot IC (2004) A new prognostic staging system for rectal cancer. Ann Surg 240:832–839

    Article  PubMed  Google Scholar 

  23. Deans GT, Heatley M, Anderson N, Patterson CC, Rowlands BJ, Parks TG, Spence RA (1994) Jass’ classification revisited. J Am Coll Surg 179:11–17

    PubMed  CAS  Google Scholar 

  24. Jass JR, Ajioka Y, Allen JP, Chan YF, Cohen RJ, Nixon JM, Radojkovic M, Restall AP, Stables SR, Zwi LJ (1996) Assessment of invasive growth pattern and lymphocytic infiltration in colorectal cancer. Histopathology 28:543–548

    Article  PubMed  CAS  Google Scholar 

  25. Sternberg A, Sibirsky O, Cohen D, Blumenson LE, Petrelli NJ (1999) Validation of a new classification system for curatively resected colorectal adenocarcinoma. Cancer 86:782–792

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This work was supported by the Dong-A University Research Fund in 2004.

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Correspondence to Hong-Jo Choi.

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Choi, HJ., Park, KJ., Shin, JS. et al. Tumor budding as a prognostic marker in stage-III rectal carcinoma. Int J Colorectal Dis 22, 863–868 (2007). https://doi.org/10.1007/s00384-006-0249-8

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