Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1997;76(10):1288–1292. doi: 10.1038/bjc.1997.550

Lack of cyclin E immunoreactivity in non-malignant breast and association with proliferation in breast cancer.

K A Scott 1, R A Walker 1
PMCID: PMC2228161  PMID: 9374373

Abstract

Cyclin E is a G1 cyclin that is essential for the transition from G1 to S phase in the cell cycle. Alterations to cyclin E expression or regulation could be important in tumorigenesis. Previous immunohistochemical and immunoblotting studies have investigated the expression of cyclin E in breast carcinomas. In this study, cyclin E has been investigated in a range of non-malignant and malignant breast using immunohistochemistry. Normal and benign tissue from pre- and post-menopausal women (39 cases), non-involved tissue from cancer-containing breasts (47 cases), ductal carcinoma in situ (22 cases) and invasive breast carcinomas (109 cases) have been examined. There was no reactivity in any of the non-malignant breast. Only one ductal carcinoma in situ contained more than 5% reactive cells. A total of 28% of invasive carcinomas had > 5% of reactive cells (range 0-88% positive cells, mean 12.59%, median 1.0%). A significant association was found with poorer differentiation (P < 0.001), high MIB1 index (P < 0.001), lack of oestrogen receptor (0.05 > P > 0.025) and the presence of p53 protein (0.05 > P > 0.025). Virtually all cases with cyclin E and p53 were poorly differentiated. The presence of cyclin E is therefore only found in breast malignancies and is associated with more aggressive features, including high proliferation.

Full text

PDF
1288

Images in this article

Selected References

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

  1. Alpers C. E., Wellings S. R. The prevalence of carcinoma in situ in normal and cancer-associated breasts. Hum Pathol. 1985 Aug;16(8):796–807. doi: 10.1016/s0046-8177(85)80251-3. [DOI] [PubMed] [Google Scholar]
  2. Cattoretti G., Becker M. H., Key G., Duchrow M., Schlüter C., Galle J., Gerdes J. Monoclonal antibodies against recombinant parts of the Ki-67 antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol. 1992 Dec;168(4):357–363. doi: 10.1002/path.1711680404. [DOI] [PubMed] [Google Scholar]
  3. Dulić V., Lees E., Reed S. I. Association of human cyclin E with a periodic G1-S phase protein kinase. Science. 1992 Sep 25;257(5078):1958–1961. doi: 10.1126/science.1329201. [DOI] [PubMed] [Google Scholar]
  4. Dupont W. D., Page D. L. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med. 1985 Jan 17;312(3):146–151. doi: 10.1056/NEJM198501173120303. [DOI] [PubMed] [Google Scholar]
  5. Dutta A., Chandra R., Leiter L. M., Lester S. Cyclins as markers of tumor proliferation: immunocytochemical studies in breast cancer. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5386–5390. doi: 10.1073/pnas.92.12.5386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Elston C. W., Ellis I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x. [DOI] [PubMed] [Google Scholar]
  7. Gillett C., Smith P., Gregory W., Richards M., Millis R., Peters G., Barnes D. Cyclin D1 and prognosis in human breast cancer. Int J Cancer. 1996 Apr 22;69(2):92–99. doi: 10.1002/(SICI)1097-0215(19960422)69:2<92::AID-IJC4>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  8. Gretarsdottir S., Tryggvadottir L., Jonasson J. G., Sigurdsson H., Olafsdottir K., Agnarsson B. A., Ogmundsdottir H., Eyfjörd J. E. TP53 mutation analyses on breast carcinomas: a study of paraffin-embedded archival material. Br J Cancer. 1996 Aug;74(4):555–561. doi: 10.1038/bjc.1996.400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hunter T., Pines J. Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell. 1994 Nov 18;79(4):573–582. doi: 10.1016/0092-8674(94)90543-6. [DOI] [PubMed] [Google Scholar]
  10. Isola J., Visakorpi T., Holli K., Kallioniemi O. P. Association of overexpression of tumor suppressor protein p53 with rapid cell proliferation and poor prognosis in node-negative breast cancer patients. J Natl Cancer Inst. 1992 Jul 15;84(14):1109–1114. doi: 10.1093/jnci/84.14.1109. [DOI] [PubMed] [Google Scholar]
  11. Keyomarsi K., Conte D., Jr, Toyofuku W., Fox M. P. Deregulation of cyclin E in breast cancer. Oncogene. 1995 Sep 7;11(5):941–950. [PubMed] [Google Scholar]
  12. Keyomarsi K., O'Leary N., Molnar G., Lees E., Fingert H. J., Pardee A. B. Cyclin E, a potential prognostic marker for breast cancer. Cancer Res. 1994 Jan 15;54(2):380–385. [PubMed] [Google Scholar]
  13. Keyomarsi K., Pardee A. B. Redundant cyclin overexpression and gene amplification in breast cancer cells. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1112–1116. doi: 10.1073/pnas.90.3.1112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Koff A., Giordano A., Desai D., Yamashita K., Harper J. W., Elledge S., Nishimoto T., Morgan D. O., Franza B. R., Roberts J. M. Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle. Science. 1992 Sep 18;257(5077):1689–1694. doi: 10.1126/science.1388288. [DOI] [PubMed] [Google Scholar]
  15. La Thangue N. B. DRTF1/E2F: an expanding family of heterodimeric transcription factors implicated in cell-cycle control. Trends Biochem Sci. 1994 Mar;19(3):108–114. doi: 10.1016/0968-0004(94)90202-x. [DOI] [PubMed] [Google Scholar]
  16. Lagios M. D. Duct carcinoma in situ. Pathology and treatment. Surg Clin North Am. 1990 Aug;70(4):853–871. doi: 10.1016/s0039-6109(16)45185-6. [DOI] [PubMed] [Google Scholar]
  17. Nevins J. R. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science. 1992 Oct 16;258(5081):424–429. doi: 10.1126/science.1411535. [DOI] [PubMed] [Google Scholar]
  18. Nielsen N. H., Arnerlöv C., Emdin S. O., Landberg G. Cyclin E overexpression, a negative prognostic factor in breast cancer with strong correlation to oestrogen receptor status. Br J Cancer. 1996 Sep;74(6):874–880. doi: 10.1038/bjc.1996.451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Norton A. J., Jordan S., Yeomans P. Brief, high-temperature heat denaturation (pressure cooking): a simple and effective method of antigen retrieval for routinely processed tissues. J Pathol. 1994 Aug;173(4):371–379. doi: 10.1002/path.1711730413. [DOI] [PubMed] [Google Scholar]
  20. Ohtsubo M., Theodoras A. M., Schumacher J., Roberts J. M., Pagano M. Human cyclin E, a nuclear protein essential for the G1-to-S phase transition. Mol Cell Biol. 1995 May;15(5):2612–2624. doi: 10.1128/mcb.15.5.2612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pardee A. B. G1 events and regulation of cell proliferation. Science. 1989 Nov 3;246(4930):603–608. doi: 10.1126/science.2683075. [DOI] [PubMed] [Google Scholar]
  22. Rajakariar R., Walker R. A. Pathological and biological features of mammographically detected invasive breast carcinomas. Br J Cancer. 1995 Jan;71(1):150–154. doi: 10.1038/bjc.1995.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tsai L. H., Lees E., Faha B., Harlow E., Riabowol K. The cdk2 kinase is required for the G1-to-S transition in mammalian cells. Oncogene. 1993 Jun;8(6):1593–1602. [PubMed] [Google Scholar]

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

RESOURCES