Skip to main content
Top
Published in: International Journal of Colorectal Disease 8/2007

01-08-2007 | Original Article

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

Authors: Hong-Jo Choi, Ki-Jae Park, Jong-Sok Shin, Mee-Sook Roh, Hyuk-Chan Kwon, Hyung-Sik Lee

Published in: International Journal of Colorectal Disease | Issue 8/2007

Login to get access

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.
Literature
1.
go back to reference Jass JR, Morson BC (1987) Reporting colorectal cancer. Br J Clin Pathol 40:1016–1023CrossRef Jass JR, Morson BC (1987) Reporting colorectal cancer. Br J Clin Pathol 40:1016–1023CrossRef
2.
go back to reference Fielding LP, Phillips RK, Fry JS, Hittinger R (1986) Prediction of outcome after curative resection for large bowel cancer. Lancet 18:904–907CrossRef Fielding LP, Phillips RK, Fry JS, Hittinger R (1986) Prediction of outcome after curative resection for large bowel cancer. Lancet 18:904–907CrossRef
3.
go back to reference 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 214:11–18PubMed 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 214:11–18PubMed
4.
go back to reference Harrison JC, Dean PJ, El-Zeky F, Vander Zwaag R (1994) From Dukes through Jass: pathological prognostic indicators in rectal cancer. Hum Pathol 25:498–505PubMedCrossRef Harrison JC, Dean PJ, El-Zeky F, Vander Zwaag R (1994) From Dukes through Jass: pathological prognostic indicators in rectal cancer. Hum Pathol 25:498–505PubMedCrossRef
5.
go back to reference 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 63:539–543PubMedCrossRef 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 63:539–543PubMedCrossRef
6.
go back to reference Hase K, Shatney C, Johnson D, Trollope M, Vierra M (1993) Prognostic value of tumor “budding” in patients with colorectal cancer. Dis Colon Rectum 36:627–635PubMedCrossRef Hase K, Shatney C, Johnson D, Trollope M, Vierra M (1993) Prognostic value of tumor “budding” in patients with colorectal cancer. Dis Colon Rectum 36:627–635PubMedCrossRef
7.
go back to reference Gabbert H (1985) Mechanism of tumor invasion: evidence from in vivo observations. Cancer Metastasis Rev 4:293–309PubMedCrossRef Gabbert H (1985) Mechanism of tumor invasion: evidence from in vivo observations. Cancer Metastasis Rev 4:293–309PubMedCrossRef
8.
go back to reference Okuyama T, Oya M, Ishikawa H (2003) Budding as a useful prognostic marker in pT3 well- or moderately-differentiated rectal adenocarcinoma. J Surg Oncol 83:42–47PubMedCrossRef Okuyama T, Oya M, Ishikawa H (2003) Budding as a useful prognostic marker in pT3 well- or moderately-differentiated rectal adenocarcinoma. J Surg Oncol 83:42–47PubMedCrossRef
9.
go back to reference 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 40:127–132PubMedCrossRef 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 40:127–132PubMedCrossRef
10.
go back to reference Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170PubMed Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170PubMed
11.
go back to reference Cox DR (1972) Regression models and life tables. J R Stat Soc 34:187–220 Cox DR (1972) Regression models and life tables. J R Stat Soc 34:187–220
12.
go back to reference Nowell PC (1986) Mechanisms of tumor progression. Cancer Res 46:2203–2207PubMed Nowell PC (1986) Mechanisms of tumor progression. Cancer Res 46:2203–2207PubMed
13.
14.
go back to reference Gabbert H (1985) Mechanism of tumor invasion: evidence from in vivo observations. Cancer Metastasis Rev 4:293–309PubMedCrossRef Gabbert H (1985) Mechanism of tumor invasion: evidence from in vivo observations. Cancer Metastasis Rev 4:293–309PubMedCrossRef
15.
go back to reference 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 88:708–717PubMedCrossRef 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 88:708–717PubMedCrossRef
16.
go back to reference 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 55:4132–4139PubMed 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 55:4132–4139PubMed
17.
go back to reference 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 92:2539–2546PubMedCrossRef 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 92:2539–2546PubMedCrossRef
18.
go back to reference 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 92:1074–1081PubMed 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 92:1074–1081PubMed
19.
go back to reference 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 94:2882–2891PubMedCrossRef 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 94:2882–2891PubMedCrossRef
20.
go back to reference Ueno H, Mochizuki H, Hatsuse K, Hase K, Yamamoto T (2000) Indicators for treatment strategies of colorectal liver metastases. Ann Surg 231:59–66PubMedCrossRef Ueno H, Mochizuki H, Hatsuse K, Hase K, Yamamoto T (2000) Indicators for treatment strategies of colorectal liver metastases. Ann Surg 231:59–66PubMedCrossRef
21.
go back to reference 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 48:1597–1602PubMedCrossRef 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 48:1597–1602PubMedCrossRef
22.
go back to reference Ueno H, Price AB, Wilkinson KH, Jass JR, Mochizuki H, Talbot IC (2004) A new prognostic staging system for rectal cancer. Ann Surg 240:832–839PubMedCrossRef Ueno H, Price AB, Wilkinson KH, Jass JR, Mochizuki H, Talbot IC (2004) A new prognostic staging system for rectal cancer. Ann Surg 240:832–839PubMedCrossRef
23.
go back to reference Deans GT, Heatley M, Anderson N, Patterson CC, Rowlands BJ, Parks TG, Spence RA (1994) Jass’ classification revisited. J Am Coll Surg 179:11–17PubMed Deans GT, Heatley M, Anderson N, Patterson CC, Rowlands BJ, Parks TG, Spence RA (1994) Jass’ classification revisited. J Am Coll Surg 179:11–17PubMed
24.
go back to reference 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 28:543–548PubMedCrossRef 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 28:543–548PubMedCrossRef
25.
go back to reference Sternberg A, Sibirsky O, Cohen D, Blumenson LE, Petrelli NJ (1999) Validation of a new classification system for curatively resected colorectal adenocarcinoma. Cancer 86:782–792PubMedCrossRef Sternberg A, Sibirsky O, Cohen D, Blumenson LE, Petrelli NJ (1999) Validation of a new classification system for curatively resected colorectal adenocarcinoma. Cancer 86:782–792PubMedCrossRef
Metadata
Title
Tumor budding as a prognostic marker in stage-III rectal carcinoma
Authors
Hong-Jo Choi
Ki-Jae Park
Jong-Sok Shin
Mee-Sook Roh
Hyuk-Chan Kwon
Hyung-Sik Lee
Publication date
01-08-2007
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 8/2007
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-006-0249-8

Other articles of this Issue 8/2007

International Journal of Colorectal Disease 8/2007 Go to the issue

Letter to the Editor

More than just skin deep!