Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Feb;73(3):386–390. doi: 10.1038/bjc.1996.66

Creatine kinase BB isoenzyme levels in tumour cytosols and survival of breast cancer patients.

N Zarghami 1, M Giai 1, H Yu 1, R Roagna 1, R Ponzone 1, D Katsaros 1, P Sismondi 1, E P Diamandis 1
PMCID: PMC2074443  PMID: 8562347

Abstract

Creatinine kinase BB (CK-BB) is elevated in many tumours including those of the breast. We have recently described a new, highly sensitive and specific method for measuring CK-BB, based on monoclonal antibodies and time-resolved fluorometry. Using this method, we quantitated CK-BB in 172 breast tumour cytosols and examined the associations between CK-BB and other clinicopathological variables and patient survival. High CK-BB levels were seen more frequently in tumours from patients who were younger (age < 50 years), patients who qualified for chemotherapy and patients with oestrogen receptor-positive tumours. No association was seen between CK-BB and tumour stage, grade, size, histological type or the progesterone receptor. In univariate analysis, the risk of relapse or death was higher in the group with tumours containing high CK-BB levels but the difference did not reach statistical significance. In multivariate analysis, the risk of death was statistically significantly higher in the high-CK-BB group. Analysis of subsets of patients revealed that patients with oestrogen receptor-negative cancer have higher risk of death if their tumours contain high levels of CK-BB. Our data suggest that, in general, CK-BB is associated with more aggressive tumours but its value as a prognostic indicator is limited. CK-BB content of breast tumours may be more useful as an aid in selecting therapy directed at inhibiting this enzyme activity and thus depriving tumour cells of their energy source.

Full text

PDF
386

Selected References

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

  1. Arenas J., Diaz A. E., Alcaide M. J., Santos I., Martínez A., Culebras J. M. Serum CK-BB as a tumor marker in patients with carcinoma confirmed histologically. Clin Chim Acta. 1989 Jun 30;182(2):183–193. doi: 10.1016/0009-8981(89)90077-6. [DOI] [PubMed] [Google Scholar]
  2. BLOOM H. J., RICHARDSON W. W. Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer. 1957 Sep;11(3):359–377. doi: 10.1038/bjc.1957.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bach F., Bach F. W., Pedersen A. G., Larsen P. M., Dombernowsky P. Creatine kinase-BB in the cerebrospinal fluid as a marker of CNS metastases and leptomeningeal carcinomatosis in patients with breast cancer. Eur J Cancer Clin Oncol. 1989 Dec;25(12):1703–1709. doi: 10.1016/0277-5379(89)90338-6. [DOI] [PubMed] [Google Scholar]
  4. Hopton D. S., Thorogood J., Clayden A. D., MacKinnon D. Observer variation in histological grading of breast cancer. Eur J Surg Oncol. 1989 Feb;15(1):21–23. [PubMed] [Google Scholar]
  5. Kaddurah-Daouk R., Lillie J. W., Daouk G. H., Green M. R., Kingston R., Schimmel P. Induction of a cellular enzyme for energy metabolism by transforming domains of adenovirus E1a. Mol Cell Biol. 1990 Apr;10(4):1476–1483. doi: 10.1128/mcb.10.4.1476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kaye A. M., Hallowes R., Cox S., Sluyser M. Hormone-responsive creatine kinase in normal and neoplastic mammary glands. Ann N Y Acad Sci. 1986;464:218–230. doi: 10.1111/j.1749-6632.1986.tb16006.x. [DOI] [PubMed] [Google Scholar]
  7. Malnick S. D., Shaer A., Soreq H., Kaye A. M. Estrogen-induced creatine kinase in the reproductive system of the immature female rat. Endocrinology. 1983 Nov;113(5):1907–1909. doi: 10.1210/endo-113-5-1907. [DOI] [PubMed] [Google Scholar]
  8. Martin K. J., Chen S. F., Clark G. M., Degen D., Wajima M., Von Hoff D. D., Kaddurah-Daouk R. Evaluation of creatine analogues as a new class of anticancer agents using freshly explanted human tumor cells. J Natl Cancer Inst. 1994 Apr 20;86(8):608–613. doi: 10.1093/jnci/86.8.608. [DOI] [PubMed] [Google Scholar]
  9. McGing P. G., Teeling M., McCann A., Kyne F., Carney D. N. Non-M CK--a practical measure of creatine kinase isoenzymes in cancer patients. Clin Chim Acta. 1990 Mar 15;187(3):309–315. doi: 10.1016/0009-8981(90)90116-a. [DOI] [PubMed] [Google Scholar]
  10. McGuire W. L., Clark G. M. Prognostic factors and treatment decisions in axillary-node-negative breast cancer. N Engl J Med. 1992 Jun 25;326(26):1756–1761. doi: 10.1056/NEJM199206253262607. [DOI] [PubMed] [Google Scholar]
  11. Neri B., Bartalucci S., Cataliotti L., Distante V., Tommasi M., Ciapini A. Clinical utility of the combined use of plurime tumor markers in human breast cancer. Cancer Detect Prev. 1988;13(2):115–121. [PubMed] [Google Scholar]
  12. Pentecost B. T., Mattheiss L., Dickerman H. W., Kumar S. A. Estrogen regulation of creatine kinase-B in the rat uterus. Mol Endocrinol. 1990 Jul;4(7):1000–1010. doi: 10.1210/mend-4-7-1000. [DOI] [PubMed] [Google Scholar]
  13. Reiss N. A., Kaye A. M. Identification of the major component of the estrogen-induced protein of rat uterus as the BB isozyme of creatine kinase. J Biol Chem. 1981 Jun 10;256(11):5741–5749. [PubMed] [Google Scholar]
  14. Rubery E. D., Doran J. F., Thompson R. J. Brain-type creatine kinase BB as a potential tumour marker--serum levels measured by radioimmunoassay in 1015 patients with histologically confirmed malignancies. Eur J Cancer Clin Oncol. 1982 Oct;18(10):951–956. doi: 10.1016/0277-5379(82)90243-7. [DOI] [PubMed] [Google Scholar]
  15. Scambia G., Natoli V., Panici P. B., Sica G., Mancuso S. Estrogen responsive creatine kinase in human breast cancer cells. J Cancer Res Clin Oncol. 1986;112(1):29–32. doi: 10.1007/BF00394935. [DOI] [PubMed] [Google Scholar]
  16. Scambia G., Santeusanio G., Panici P. B., Iacobelli S., Mancuso S. Immunohistochemical localization of creatine kinase BB in primary breast cancer: correlation with estrogen receptor content. J Cancer Res Clin Oncol. 1988;114(1):101–104. doi: 10.1007/BF00390493. [DOI] [PubMed] [Google Scholar]
  17. Thompson R. J., Rubery E. D., Jones H. M. Radioimmunoassay of serum creatine kinase-BB as a tumour marker in breast cancer. Lancet. 1980 Sep 27;2(8196):673–675. doi: 10.1016/s0140-6736(80)92709-9. [DOI] [PubMed] [Google Scholar]
  18. Tsung S. H. Creatine kinase activity and isoenzyme pattern in various normal tissues and neoplasms. Clin Chem. 1983 Dec;29(12):2040–2043. [PubMed] [Google Scholar]
  19. Walker M. D., Kaye A. M. mRNA for the rat uterine estrogen-induced protein. Translation in vitro and regulation by estrogen. J Biol Chem. 1981 Jan 10;256(1):23–26. [PubMed] [Google Scholar]
  20. Wallimann T., Wyss M., Brdiczka D., Nicolay K., Eppenberger H. M. Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. Biochem J. 1992 Jan 1;281(Pt 1):21–40. doi: 10.1042/bj2810021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zarghami N., Yu H., Diamandis E. P., Sutherland D. J. Quantification of creatine kinase BB isoenzyme in tumor cytosols and serum with an ultrasensitive time-resolved immunofluorometric technique. Clin Biochem. 1995 Jun;28(3):243–253. doi: 10.1016/0009-9120(95)00010-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES