Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Feb;79(3-4):577–581. doi: 10.1038/sj.bjc.6690091

Low tumour cell proliferation at the invasive margin is associated with a poor prognosis in Dukes' stage B colorectal cancers

R Palmqvist 1, P Sellberg 1, Å Öberg 2, B Tavelin 3, J N Rutegård 2,4, R Stenling 1
PMCID: PMC2362413  PMID: 10027333

Abstract

The conflicting results about the prognostic impact of tumour cell proliferation in colorectal cancer might be explained by the heterogeneity observed within these tumours. We have investigated whether a systematic spatial heterogeneity exists between different compartments, and whether the presence of such a systematic heterogeneity has any impact on survival. Fifty-six Dukes' stage B colorectal cancers were carefully morphometrically quantified with respect to the immunohistochemical expression of the proliferative marker Ki-67 at both the luminal border and the invasive margin. The proliferative activity was significantly higher at the luminal border compared with the invasive margin (P < 0.001), although the two compartments were also significantly correlated with each other. Tumours with low proliferation at the invasive margin had a significantly poorer prognosis both in univariate (P = 0.014) and in multivariate survival analyses (P = 0.042). We conclude that Dukes' B colorectal cancers exhibit a systematic spatial heterogeneity with respect to proliferation, and tumours with low proliferation at the invasive margin had a poor prognosis. The present data independently confirm recent results from the authors, and provide new insights into the understanding of tumour cell proliferation in colorectal cancer. © 1999 Cancer Research Campaign

Keywords: cell proliferation, Ki-67, heterogeneity, invasion, colorectal carcinoma

Full Text

The Full Text of this article is available as a PDF (71.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bauer K. D., Bagwell C. B., Giaretti W., Melamed M., Zarbo R. J., Witzig T. E., Rabinovitch P. S. Consensus review of the clinical utility of DNA flow cytometry in colorectal cancer. Cytometry. 1993;14(5):486–491. doi: 10.1002/cyto.990140506. [DOI] [PubMed] [Google Scholar]
  2. Butler R. N., Bruhn B., Pascoe V., Fettman M. J., Roberts-Thomson I. C. Regional factors affecting proliferation in the large intestine of the rat. Proc Soc Exp Biol Med. 1992 May;200(1):133–137. doi: 10.3181/00379727-200-43405. [DOI] [PubMed] [Google Scholar]
  3. Evan G. Cancer--a matter of life and cell death. Int J Cancer. 1997 May 29;71(5):709–711. doi: 10.1002/(sici)1097-0215(19970529)71:5<709::aid-ijc2>3.0.co;2-v. [DOI] [PubMed] [Google Scholar]
  4. Gundersen H. J., Bendtsen T. F., Korbo L., Marcussen N., Møller A., Nielsen K., Nyengaard J. R., Pakkenberg B., Sørensen F. B., Vesterby A. Some new, simple and efficient stereological methods and their use in pathological research and diagnosis. APMIS. 1988 May;96(5):379–394. doi: 10.1111/j.1699-0463.1988.tb05320.x. [DOI] [PubMed] [Google Scholar]
  5. Hall P. A., Richards M. A., Gregory W. M., d'Ardenne A. J., Lister T. A., Stansfeld A. G. The prognostic value of Ki67 immunostaining in non-Hodgkin's lymphoma. J Pathol. 1988 Mar;154(3):223–235. doi: 10.1002/path.1711540305. [DOI] [PubMed] [Google Scholar]
  6. Harlow S. P., Eriksen B. L., Poggensee L., Chmiel J. S., Scarpelli D. G., Murad T., Bauer K. D. Prognostic implications of proliferative activity and DNA aneuploidy in Astler-Coller Dukes stage C colonic adenocarcinomas. Cancer Res. 1991 May 1;51(9):2403–2409. [PubMed] [Google Scholar]
  7. Hartwell L. H., Kastan M. B. Cell cycle control and cancer. Science. 1994 Dec 16;266(5192):1821–1828. doi: 10.1126/science.7997877. [DOI] [PubMed] [Google Scholar]
  8. Jass J. R., Atkin W. S., Cuzick J., Bussey H. J., Morson B. C., Northover J. M., Todd I. P. The grading of rectal cancer: historical perspectives and a multivariate analysis of 447 cases. Histopathology. 1986 May;10(5):437–459. doi: 10.1111/j.1365-2559.1986.tb02497.x. [DOI] [PubMed] [Google Scholar]
  9. Koha M., Caspersson T. O., Wikström B., Brismar B. Heterogeneity of DNA distribution pattern in colorectal carcinoma. A microspectrophotometric study of fine needle aspirates. Anal Quant Cytol Histol. 1990 Oct;12(5):348–351. [PubMed] [Google Scholar]
  10. Kubota Y., Petras R. E., Easley K. A., Bauer T. W., Tubbs R. R., Fazio V. W. Ki-67-determined growth fraction versus standard staging and grading parameters in colorectal carcinoma. A multivariate analysis. Cancer. 1992 Dec 1;70(11):2602–2609. doi: 10.1002/1097-0142(19921201)70:11<2602::aid-cncr2820701106>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  11. Lehy T., Abitbol J. L., Mignon M. Influence de la préparation rectale par lavement sur la prolifération cellulaire dans la muqueuse rectale normale de l'homme. Gastroenterol Clin Biol. 1984 Mar;8(3):216–221. [PubMed] [Google Scholar]
  12. Lindmark G., Glimelius B., Påhlman L., Enblad P. Heterogeneity in ploidy and S-phase fraction in colorectal adenocarcinomas. Int J Colorectal Dis. 1991 May;6(2):115–120. doi: 10.1007/BF00300207. [DOI] [PubMed] [Google Scholar]
  13. Mullan F. J., Wilson H. K., Majury C. W., Mills J. O., Cromie A. J., Campbell G. R., McKelvey S. T. Bile acids and the increased risk of colorectal tumours after truncal vagotomy. Br J Surg. 1990 Oct;77(10):1085–1090. doi: 10.1002/bjs.1800771004. [DOI] [PubMed] [Google Scholar]
  14. Neoptolemos J. P., Oates G. D., Newbold K. M., Robson A. M., McConkey C., Powell J. Cyclin/proliferation cell nuclear antigen immunohistochemistry does not improve the prognostic power of Dukes' or Jass' classifications for colorectal cancer. Br J Surg. 1995 Feb;82(2):184–187. doi: 10.1002/bjs.1800820214. [DOI] [PubMed] [Google Scholar]
  15. Nichols G. E., Frierson H. F., Jr, Boyd J. C., Hanigan M. H. Automated immunohistochemical assay for estrogen receptor status in breast cancer using monoclonal antibody CC4-5 on the Ventana ES. Am J Clin Pathol. 1996 Sep;106(3):332–338. doi: 10.1093/ajcp/106.3.332. [DOI] [PubMed] [Google Scholar]
  16. Pietra N., Sarli L., Sansebastiano G., Jotti G. S., Peracchia A. Prognostic value of ploidy, cell proliferation kinetics, and conventional clinicopathologic criteria in patients with colorectal carcinoma: a prospective study. Dis Colon Rectum. 1996 May;39(5):494–503. doi: 10.1007/BF02058700. [DOI] [PubMed] [Google Scholar]
  17. Rew D. A. Cell proliferation, tumour growth and clinical outcome: gains and losses in intestinal cancer. Ann R Coll Surg Engl. 1993 Nov;75(6):397–404. [PMC free article] [PubMed] [Google Scholar]
  18. Roncucci L., Pedroni M., Scalmati A., Bormioli M. L., Sassatelli R., Fante R., Losi L., Di Gregorio C., Petocchi B., Ponz de Leon M. Cell kinetics evaluation of colorectal tumors after in vivo administration of bromodeoxyuridine. Int J Cancer. 1992 Dec 2;52(6):856–861. doi: 10.1002/ijc.2910520604. [DOI] [PubMed] [Google Scholar]
  19. Shepherd N. A., Richman P. I., England J. Ki-67 derived proliferative activity in colorectal adenocarcinoma with prognostic correlations. J Pathol. 1988 Jul;155(3):213–219. doi: 10.1002/path.1711550306. [DOI] [PubMed] [Google Scholar]
  20. Taniyama K., Sasaki N., Wada S., Sasaki M., Miyoshi N., Nakai H., Kodama S., Nakatsuka H., Tahara E. Comparison of proliferative activities and metastases between two subtypes classified at the deeply infiltrating sites of colorectal moderately differentiated adenocarcinomas. Pathol Int. 1996 Mar;46(3):195–203. doi: 10.1111/j.1440-1827.1996.tb03598.x. [DOI] [PubMed] [Google Scholar]
  21. Taniyama K., Suzuki H., Matsumoto M., Hakamada K., Toyama K., Tahara E. Relationships between nodal status and cell kinetics, DNA ploidy pattern and histopathology of the deeply infiltrating sites in colorectal adenocarcinoma. Acta Pathol Jpn. 1993 Oct;43(10):590–596. doi: 10.1111/j.1440-1827.1993.tb03235.x. [DOI] [PubMed] [Google Scholar]
  22. Witzig T. E., Loprinzi C. L., Gonchoroff N. J., Reiman H. M., Cha S. S., Wieand H. S., Katzmann J. A., Paulsen J. K., Moertel C. G. DNA ploidy and cell kinetic measurements as predictors of recurrence and survival in stages B2 and C colorectal adenocarcinoma. Cancer. 1991 Aug 15;68(4):879–888. doi: 10.1002/1097-0142(19910815)68:4<879::aid-cncr2820680434>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  23. Zarbo R. J., Nakhleh R. E., Brown R. D., Kubus J. J., Ma C. K., Mackowiak P. Prognostic significance of DNA ploidy and proliferation in 309 colorectal carcinomas as determined by two-color multiparametric DNA flow cytometry. Cancer. 1997 Jun 1;79(11):2073–2086. [PubMed] [Google Scholar]
  24. al-Sheneber I. F., Shibata H. R., Sampalis J., Jothy S. Prognostic significance of proliferating cell nuclear antigen expression in colorectal cancer. Cancer. 1993 Mar 15;71(6):1954–1959. doi: 10.1002/1097-0142(19930315)71:6<1954::aid-cncr2820710605>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES