Skip to main content
SpringerLink
Log in

Prognostic value of ploidy, cell proliferation kinetics, and conventional clinicopathologic criteria in patients with colorectal carcinoma

A prospective study

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

Abstract

PURPOSE: The aim of this study was to obtain additional biologic determinants that may be of use in segregating into subgroups with different prognosis patients with similarly staged colorectal cancers. METHODS: Between 1989 and 1991, a prospective study of prognostic factors has been performed in a group of 98 consecutive, unselected patients who underwent curative resections for primary untreated large bowel carcinoma. The fate of all patients is known at three years after operation. Clinical and pathologic data were recorded at the time of presentation and operation, and patients have been the subjects of regular follow-up. Tumor DNA content was determined by flow cytometry, and cell proliferative activity was determined by autoradiography with tritiated thymidine labeling index (LI). RESULTS: Univariate analysis revealed that the most important predictors of survival (P<0.001) were the presence of positive lymph nodes, the presence of preoperative complications, Dukes stage, and LI. The multivariate analysis showed that Dukes stage (P<0.002) and LI(P<0.0001) were the only factors significantly related to survival. Disease-free survival was influenced significantly by Dukes stage (P<0.001), LI, according to the classification in the two groups of high and low proliferative activity, respectively, (P<0.0001), LI, calculated as a continuous variable (P<0.0002), and the presence of lymph node metastases (P<0.003). Outcome (favorable/unfavorable) was influenced significantly by Dukes stage (P<0.0001) and LI (P<0.0001). Concordance for each patient between Dukes stage and outcome was 73.1 percent and between LI, calculated as a continuous variable, and outcome was 74.1 percent. If, on the other hand, Dukes stage and LI are used together, concordance with outcome reaches 89.2 percent. CONCLUSION: We can conclude that, from a practical point of view, LI is an essential factor that must be combined with pathologic variables for a better prediction of patient outcome.

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

Similar content being viewed by others

References

  1. Dukes C. The classification of cancer of the rectum. J Pathol Bacteriol 1932;35:323–32.

    Google Scholar 

  2. Cohen AM, Shank B, Friedman MA. Colorectal cancer. In: DeVita VT Jr, Hellmann S, Rosenberg SA, eds. Cancer: principles and practice of oncology. Philadelphia: JB Lippincott, 1989:895–964.

    Google Scholar 

  3. Friedlander ML, Hedley DW, Taylor IW. Clinical and biological significance of aneuploidy in human tumours. J Clin Pathol 1984;37:961–74.

    PubMed  Google Scholar 

  4. Hiddemann W, Von Bassewitz DB, Kleinemeier HJ,et al. DNA stemline heterogeneity in colorectal cancer. Cancer 1986;58:258–63.

    PubMed  Google Scholar 

  5. Koss GK, Greenebaum L. Measuring DNA in humam cancer. JAMA 1986;255:3158–9.

    PubMed  Google Scholar 

  6. Quirke P, Dyson JE. Flow cytometry: methodology and applications in pathology. J Pathol 1986;149:79–87.

    PubMed  Google Scholar 

  7. Armitage NC, Robias RA, Evans DF,et al. The influence of tumor cell DNA abnormalities on survival in colorectal cancer. Br J Surg 1985;72:828–30.

    PubMed  Google Scholar 

  8. Melamed MR, Enker WE, Banner P, Janov AJ, Kessler G, Darzynkiewicz Z. Flow citometry of colorectal carcinoma with three year follow-up. Dis Colon Rectum 1986;29:184–6.

    PubMed  Google Scholar 

  9. Frankfurt OS, Arbuck SG, Chin JL. Prognostic applications of DNA flow citometry for human solid tumors. Ann N Y Acad Sci 1986;87:276–290.

    Google Scholar 

  10. Kokal W, Sheibani K, Terz J, Harada R. Tumor DNA content in the prognosis of colorectal carcinoma. JAMA 1986;255:3123–7.

    PubMed  Google Scholar 

  11. Goh HS, Jass JR, Atkin WS, Cuzick J, Northover JM. Value of flow cytometric determination of ploidy as a guide to prognosis in operable rectal cancer: a multivariate analysis. Int J Colorectal Dis 1987;2:17–21.

    PubMed  Google Scholar 

  12. Emdin SO, Stenlig R, Roos G. Prognostic value of DNA content in colorectal carcinoma: a flow citometric study with some methodologic aspects. Cancer 1987;60:1282–7.

    PubMed  Google Scholar 

  13. Grandjouan S. Cancers colo-rectaux a l'heure de la genetique moleculaire. Presse Med 1994;23:929–30.

    Google Scholar 

  14. Gonzales Aguilera JJ, Fernandez-Peralta A, Vazquez R, Palicio M, Maillo C, Moreno Azcoita M. Genome instability in sporadic colorectal adenocarcinomas. Br J Surg 1994;81(Suppl 1):29.

    Google Scholar 

  15. Wolley RC, Schreiber K, Koss LG,et al. DNA distribution In human colon carcinomas and its relationship to clinical behaviour. J Natl Cancer Inst 1982;69:15–22.

    PubMed  Google Scholar 

  16. Quirke P, Dixon MF, Clayden AD,et al. Prognostic significance of DNA aneuploidy and cell proliferation in rectal carcinoma. J Pathol 1987;151:285–91.

    PubMed  Google Scholar 

  17. Scott NA, Rainwater LM, Wieand HS,et al. The relative prognostic value of flow cytometric DNA analysis and conventional clinicopathologic criteria in patients with operable rectal carcinoma. Dis Colon Rectum 1987;30:513–20.

    PubMed  Google Scholar 

  18. Jones DJ, Moore M, Schofield PF. Refining the prognostic significance of DNA ploidy status in colorectal cancer: a prospective flow cytometric study. Int J Cancer 1988;41:206–10.

    PubMed  Google Scholar 

  19. Wiggers T, Arends JW, Schutte B, Volovics L, Bosnian FT. A multivariate analysis of pathologic prognostic indicators in large bowel cancer. Cancer 1988;61:386–95.

    PubMed  Google Scholar 

  20. Halvorsen TB, Johanessen E. DNA ploidy, tumor site and prognosis in colorectal cancer. Scand J Gastroenterol 1990;25:141–8.

    PubMed  Google Scholar 

  21. Jass JR, Mukawa K, Goh HS, Love SB, Cappellaro D. Clinical importance of DNA content in rectal cancer measured by flow cytometry. J Clin Pathol 1989;42:254–259.

    PubMed  Google Scholar 

  22. Fisher ER, Sideritis RH, Sass R, Fisher B. Value of assessment of ploidy in rectal cancer. Int J Cancer 1990;45:597–603.

    PubMed  Google Scholar 

  23. Shackney SE, Smith CA, Miller BW,et al. Model for the genetic evolution of human solid tumors. Cancer Res 1898;49:3344–54.

    Google Scholar 

  24. Tribukait B, Hammarberg C, Rubio C. Ploidy and proliferation patterns in colorectal adenocarcinomas related to Dukes' classification and to histopathological differentiation. Acta Pathol Microbiol Immunol Scand [A] 1983;91:89–95.

    Google Scholar 

  25. Morson BC, Sobin LH. Histological typing of intestinal tumors: international histological classification of tumors. Geneva: WHO, 1976:14.

    Google Scholar 

  26. Turnbull RB Jr, Kyle K, Watson FR, Spratt J. Cancer of the colon: the influence of the “no touch isolation” technique on survival rates. Ann Surg 1967;166:420–7.

    PubMed  Google Scholar 

  27. Turnbull RB Jr. The no touch isolation technique of resection. JAMA 1975;231:1181–2.

    PubMed  Google Scholar 

  28. Del Bino G, Silvestrini R, Zucconi MR,et al. DNA ploidy of human breast cancer. Ann Cell Pathol 1989;1:215–23.

    Google Scholar 

  29. Costa A, Faranda A, Scalman A,et al. Autoradiographic and flow cytometric assessment of cell proliferation in primary colorectal cancer: relationship to DNA ploidy and clinicopathological features. Int J Cancer 1992;50:719–23.

    PubMed  Google Scholar 

  30. Agresti A. Analysis of ordinal categorical data. New York: Wiley & Sons, 1984.

    Google Scholar 

  31. Cox DR. regression models and life tables. J R Stat Soc B 1972;34:187–220.

    Google Scholar 

  32. Valone F, Friedman M, Wittlinger P,et al. Treatment of patients with advanced colorectal carcinomas with fluouracil alone, high-dose leucovorin plus fluouracil or segmental methotrexate, fluouracil and leucovorin: a randomized trial of the Northern California Oncology Group. J Clin Oncol 1989;7:1427–36.

    PubMed  Google Scholar 

  33. NIH consensus conference. Adjuvant therapy for patients with colon and rectal cancer. JAMA 1990;264: 1444–50.

    Google Scholar 

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

    PubMed  Google Scholar 

  35. Krooke JE, Moertel CG, Gunderson LL,et al. Effective surgical adjuvant therapy for high risk rectal carcinoma. N Engl J Med 1991;324:709–15.

    PubMed  Google Scholar 

  36. Moertel CG, Fleming TR, Mac Donald JS,et al. The intergroup study of fluorouracile plus levamisole and levamisole alone as adjuvant therapy for stage C colon cancer: a final report. Pro ASCO 1992;11:161–6.

    Google Scholar 

  37. Peracchia A, Sarli L, Carreras F, Pietra N, Longinotti E, Gafà M. Recidive locoregionali dopo chirurgia curativa per cancro del colon. Ann Ital Chir 1991;1:37–44.

    Google Scholar 

  38. Peracchia A, Sarli L, Pietra N, Carreras F, Longinotti E, Gafà M. Recidive pelviche dopo chirurgia curativa per cancro del retto. Ann Ital Chir 1991;2:151–7.

    Google Scholar 

  39. Kirklin JW, Dockerty MB, Waugh JM. The role of peritoneal reflection in the prognosis of carcinoma of the rectum and sigmoid colon. Surg Gynecol Obstet 1949;88:326–31.

    Google Scholar 

  40. Astler WB, Coller FA. The prognostic significance of direct extension of carcinoma of the colon and rectum. Ann Surg 1954;139:846–52.

    PubMed  Google Scholar 

  41. Manual for staging of cancer. Chicago: American Joint Committee for cancer staging and end-results reporting, 1978.

  42. Shein PS. Adjuvant chemotherapy and radiotherapy following rectal surgery: an interim report from the Gastrointestinal Tumor Study Group (GITSG). In: Jones SE, Salmon SE, eds. Adjuvant therapy of cancer III. New York: Grune and Stratton, 1981:547–58.

    Google Scholar 

  43. Newland RC, Chapuis PH, Pheils MT, MacPherson JC. The relationship of survival to staging and grading of colorectal carcinoma: a prospective study of 503 cases. Cancer 1981;47:1424–9.

    PubMed  Google Scholar 

  44. Payne JE. International colorectal carcinoma staging and qradinq. Dis Colon Rectum 1989;32:282–5.

    PubMed  Google Scholar 

  45. Blenkinsopp WK, Stewart-Brown S, Blesovsky L, Kearney G, Fielding LP. Histopathology reporting in large bowel cancer. J Clin Pathol 1981;4:509–13.

    Google Scholar 

  46. Jass JR. Pathological staging: new methods and practical applications. Cancer Surv 1989;8:7–26.

    PubMed  Google Scholar 

  47. Shapiro HM. Flow cytometry of DNA content and other indicators of proliferative activity. Arch Pathol Lab Med 1989;113:591–7.

    PubMed  Google Scholar 

  48. Moran MR, Rothenberger DA, Gallo RA, Goldberg SM, James EC. Multifactorial analysis of local recurrences in rectal cancer, including DNA ploidy studies: a predictive model. World J Surg 1993;17:801–5.

    PubMed  Google Scholar 

  49. Rognum TO, Thorud E, Lund E. Clinical behaviour in large bowel carcinoma patients with different DNA ploidy pattern [abstract], Budapest: Atti XIV International Cancer Congress, 1986;2439.

  50. Sasaki K, Hashimoto T, Kawachino K, Takahashi M. Intratumoral regional differences in DNA ploidy of gastrointestinal carcinomas. Cancer 1988;62:2569–75.

    PubMed  Google Scholar 

  51. Deschner EE, Maskens AP. Significance of the labeling index and labeling distribution as kinetic parameters in colorectal mucosa of cancer patients and DMH treated animals. Cancer 1982;50:1136–41.

    PubMed  Google Scholar 

  52. Silvestrini R, Daidone MG, Valagussa P, Di Fronzo G, Mezzanotte G, Bonadonna G. Cell kinetics as a prognostic indicator in node-negative breast cancer. Eur J Cancer Clin Oncol 1989;25:1165–71.

    PubMed  Google Scholar 

  53. Seckinger D, Sugarbaker E, Frankfurt O. DNA content in human cancer. Arch Pathol Lab Med 1980;113; 619–26.

    Google Scholar 

  54. Deschner EE, Lipkin M, Solomon C. Study of human rectal epithelial cellsin vitro. II.3H-Thymidine incorporation into polyps and adjacent mucosa. J Natl Cancer Inst 1966;36:849–55.

    Google Scholar 

  55. Bleiberg H, Mainguet P, Galnd P. Cell renewal in familiar polyposis: comparison between polyps and adjacent healthy mucosa. Gastroenterology 1972;63:240–5.

    PubMed  Google Scholar 

  56. Lipkin M, Blattner WE, Fraumeni JF, Lynch HT, Deschner EE, Winawer S. Tritiated thymidine labeling distribution as a marker for hereditary predisposition to colon cancer. Cancer Res 1983;43:1899–1904.

    PubMed  Google Scholar 

  57. Kanemitsu T, Koike A, Yamamoto S. Study of the cell proliferation kinetics in ulcerative colitis, adenomatous polyps and cancer. Cancer 1985;56:1094–8.

    PubMed  Google Scholar 

  58. Lipkin M, Newmark MS. Effect of added dietary calcium on colonic epithelial cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med 1985;33:14381–4.

    Google Scholar 

  59. Bleiberg H, Buyse M, Galnd P. Cell kinetic indicators of premalignant stages of colorectal cancer. Cancer 1985;56:124–9.

    PubMed  Google Scholar 

  60. Silvestrini R, Faranda A, Costa A. DNA ploidy and cell kinetics in human colorectal carcinomas. J Surg Oncol 1991;2:4–8.

    Google Scholar 

  61. Silvestrini R, Costa A, Gennari L, Doci R, Bombardieri E, Bombelli L Cell kinetics of hepatic metastases as prognostic marker in patients with advanced colorectal carcinoma. HPB Surg 1990;2:135–44.

    PubMed  Google Scholar 

  62. Higgins GA, Lee CE, Dwight RW, Keehn RJ. The case for adjuvant 5FU in colorectal cancer. Cancer Clin Trails 1978;1:35–9.

    Google Scholar 

  63. Grace TB, Moss SE. Adjuvant chemotherapy in cancer of the colon and rectum: demonstration of effectiveness of prolonged 5-FU chemotherapy in a prospective controlled randomized trial. Surg Clin North Am 1981;61:1321–9.

    PubMed  Google Scholar 

  64. Habib NA, Peck MA, Sawyer CN, Blaxland JW, Luck RJ. An analysis of the outcome of 301 malignant colorectal tumors. Dis Colon Rectum 1983;26:601–5.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of General Surgery, University of Parma, School of Medicine, Parma, Italy

    Nicola Pietra M.D., Leopoldo Sarli M.D. & Anacleto Peracchia M.D.

  2. Institute of Hygiene, University of Parma, School of Medicine, Parma, Italy

    Giuliano Sansebastiano B.S.

  3. Institute of Pathology, University of Parma, School of Medicine, Parma, Italy

    Gloria Saccani Jotti M.D.

Authors
  1. Nicola Pietra M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leopoldo Sarli M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giuliano Sansebastiano B.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gloria Saccani Jotti M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anacleto Peracchia M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

About this article

Cite this article

Pietra, N., Sarli, L., Sansebastiano, G. et al. Prognostic value of ploidy, cell proliferation kinetics, and conventional clinicopathologic criteria in patients with colorectal carcinoma. Dis Colon Rectum 39, 494–503 (1996). https://doi.org/10.1007/BF02058700

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02058700

Key words

Search

Navigation