Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1990 Mar;61(3):390–393. doi: 10.1038/bjc.1990.85

Detection of the growth fraction in colorectal tumours by a monoclonal antibody against DNA polymerase alpha.

A Yamaguchi 1, S Takegawa 1, T Ishida 1, G Nishimura 1, M Kato 1, M Kanno 1, T Kosaka 1, Y Yonemura 1, I Miyazaki 1
PMCID: PMC1971304  PMID: 2328204

Abstract

The cell kinetics of 54 colorectal tumours were examined by immunohistochemical methods, using the monoclonal antibody DNA polymerase alpha which reacts with an antigen found only in proliferating cells. The rate of DNA polymerase alpha positive cells in colorectal cancer was 44.8%, a figure that was significantly higher than the 21.9% found in colorectal adenomas. The rate of DNA polymerase alpha positive cells tended to rise as the degree of differentiation decreased according to the standard histological grading criteria for colorectal cancer. Positive cells were detected in much greater numbers in tumours with liver metastasis (55.4%) than in those without metastasis (41.7%). The rate of DNA polymerase alpha positive cells for aneuploid lesions was higher than that for lesions with a diploid pattern. The determination of growth fractions with a monoclonal antibody (DNA polymerase alpha) may be a biological marker of great prognostic significance.

Full text

PDF
390

Images in this article

Selected References

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

  1. Armitage N. C., Robins R. A., Evans D. F., Turner D. R., Baldwin R. W., Hardcastle J. D. The influence of tumour cell DNA abnormalities on survival in colorectal cancer. Br J Surg. 1985 Oct;72(10):828–830. doi: 10.1002/bjs.1800721018. [DOI] [PubMed] [Google Scholar]
  2. Baril E. F., Jenkins M. D., Brown O. E., Laszlo J., Morris H. P. DNA polymerases I and II in regenerating rat liver and Morris hepatomas. Cancer Res. 1973 Jun;33(6):1187–1193. [PubMed] [Google Scholar]
  3. Barlogie B., Raber M. N., Schumann J., Johnson T. S., Drewinko B., Swartzendruber D. E., Göhde W., Andreeff M., Freireich E. J. Flow cytometry in clinical cancer research. Cancer Res. 1983 Sep;43(9):3982–3997. [PubMed] [Google Scholar]
  4. Bensch K. G., Tanaka S., Hu S. Z., Wang T. S., Korn D. Intracellular localization of human DNA polymerase alpha with monoclonal antibodies. J Biol Chem. 1982 Jul 25;257(14):8391–8396. [PubMed] [Google Scholar]
  5. Burger P. C., Shibata T., Kleihues P. The use of the monoclonal antibody Ki-67 in the identification of proliferating cells: application to surgical neuropathology. Am J Surg Pathol. 1986 Sep;10(9):611–617. doi: 10.1097/00000478-198609000-00003. [DOI] [PubMed] [Google Scholar]
  6. Chang L. M., Bollum F. J. A comparison of associated enzyme activities in various deoxyribonucleic acid polymerases. J Biol Chem. 1973 May 25;248(10):3398–3404. [PubMed] [Google Scholar]
  7. Gerdes J., Lelle R. J., Pickartz H., Heidenreich W., Schwarting R., Kurtsiefer L., Stauch G., Stein H. Growth fractions in breast cancers determined in situ with monoclonal antibody Ki-67. J Clin Pathol. 1986 Sep;39(9):977–980. doi: 10.1136/jcp.39.9.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gerdes J., Lemke H., Baisch H., Wacker H. H., Schwab U., Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984 Oct;133(4):1710–1715. [PubMed] [Google Scholar]
  9. Gratzner H. G. Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. Science. 1982 Oct 29;218(4571):474–475. doi: 10.1126/science.7123245. [DOI] [PubMed] [Google Scholar]
  10. Kokal W. A., Duda R. B., Azumi N., Sheibani K., Kemeny M. M., Terz J. J., Harada J. R. Tumor DNA content in primary and metastatic colorectal carcinoma. Arch Surg. 1986 Dec;121(12):1434–1439. doi: 10.1001/archsurg.1986.01400120084014. [DOI] [PubMed] [Google Scholar]
  11. Lellé R. J., Heidenreich W., Stauch G., Gerdes J. The correlation of growth fractions with histologic grading and lymph node status in human mammary carcinoma. Cancer. 1987 Jan 1;59(1):83–88. doi: 10.1002/1097-0142(19870101)59:1<83::aid-cncr2820590119>3.0.co;2-i. [DOI] [PubMed] [Google Scholar]
  12. Lovett E. J., 3rd, Schnitzer B., Keren D. F., Flint A., Hudson J. L., McClatchey K. D. Application of flow cytometry to diagnostic pathology. Lab Invest. 1984 Feb;50(2):115–140. [PubMed] [Google Scholar]
  13. Masaki S., Shiku H., Kaneda T., Koiwai O., Yoshida S. Production and characterization of monoclonal antibody against 10S DNA polymerase alpha from calf thymus. Nucleic Acids Res. 1982 Aug 11;10(15):4703–4713. doi: 10.1093/nar/10.15.4703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Matsukage A., Yamaguchi M., Tanabe K., Nishizawa M., Takahashi T., Seto M., Takahashi T. Establishment of hybridoma clones which produce anti-chick embryo DNA polymerase alpha monoclonal antibodies. Gan. 1982 Dec;73(6):850–853. [PubMed] [Google Scholar]
  15. Matsukage A., Yamamoto S., Yamaguchi M., Kusakabe M., Takahashi T. Immunocytochemical localization of chick DNA polymerases alpha and beta +. J Cell Physiol. 1983 Nov;117(2):266–271. doi: 10.1002/jcp.1041170219. [DOI] [PubMed] [Google Scholar]
  16. McGurrin J. F., Doria M. I., Jr, Dawson P. J., Karrison T., Stein H. O., Franklin W. A. Assessment of tumor cell kinetics by immunohistochemistry in carcinoma of breast. Cancer. 1987 May 15;59(10):1744–1750. doi: 10.1002/1097-0142(19870515)59:10<1744::aid-cncr2820591012>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  17. Mushika M., Miwa T., Suzuoki Y., Hayashi K., Masaki S., Kaneda T. Detection of proliferative cells in dysplasia, carcinoma in situ, and invasive carcinoma of the uterine cervix by monoclonal antibody against DNA polymerase alpha. Cancer. 1988 Mar 15;61(6):1182–1186. doi: 10.1002/1097-0142(19880315)61:6<1182::aid-cncr2820610621>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  18. Nakamura H., Morita T., Masaki S., Yoshida S. Intracellular localization and metabolism of DNA polymerase alpha in human cells visualized with monoclonal antibody. Exp Cell Res. 1984 Mar;151(1):123–133. doi: 10.1016/0014-4827(84)90362-8. [DOI] [PubMed] [Google Scholar]
  19. Sarngadharan M. G., Robert-Guroff M., Gallo R. C. DNA polymerases of normal and neoplastic mammalian cells. Biochim Biophys Acta. 1978 Dec 11;516(4):419–487. doi: 10.1016/0304-419x(78)90019-7. [DOI] [PubMed] [Google Scholar]
  20. Sasaki K. Measurement of tritiated thymidine labeling index by incubation in vitro of surgically removed cervical cancer. Gan. 1977 Jun;68(3):307–313. [PubMed] [Google Scholar]
  21. Scott N. A., Grande J. P., Weiland L. H., Pemberton J. H., Beart R. W., Jr, Lieber M. M. Flow cytometric DNA patterns from colorectal cancers--how reproducible are they? Mayo Clin Proc. 1987 May;62(5):331–337. doi: 10.1016/s0025-6196(12)65435-4. [DOI] [PubMed] [Google Scholar]
  22. Tanaka S., Hu S. Z., Wang T. S., Korn D. Preparation and preliminary characterization of monoclonal antibodies against human DNA polymerase alpha. J Biol Chem. 1982 Jul 25;257(14):8386–8390. [PubMed] [Google Scholar]
  23. Weissbach A. The functional roles of mammalian DNA polymerase. Arch Biochem Biophys. 1979 Dec;198(2):386–396. doi: 10.1016/0003-9861(79)90511-3. [DOI] [PubMed] [Google Scholar]
  24. Wolley R. C., Schreiber K., Koss L. G., Karas M., Sherman A. DNA distribution in human colon carcinomas and its relationship to clinical behavior. J Natl Cancer Inst. 1982 Jul;69(1):15–22. [PubMed] [Google Scholar]
  25. Yagura T., Kozu T., Seno T., Tanaka S. Immunochemical detection of a primase activity related subunit of DNA polymerase alpha from human and mouse cells using the monoclonal antibody. Biochemistry. 1987 Dec 1;26(24):7749–7754. doi: 10.1021/bi00398a032. [DOI] [PubMed] [Google Scholar]
  26. van Dierendonck J. H., Keijzer R., van de Velde C. J., Cornelisse C. J. Nuclear distribution of the Ki-67 antigen during the cell cycle: comparison with growth fraction in human breast cancer cells. Cancer Res. 1989 Jun 1;49(11):2999–3006. [PubMed] [Google Scholar]

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

RESOURCES