Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Dec 8;82(1):167–170. doi: 10.1054/bjoc.1999.0895

Histamine, mast cells and tumour cell proliferation in breast cancer: does preoperative cimetidine administration have an effect?

P F Bowrey 1, J King 1, C Magarey 1, P Schwartz 1, P Marr 2, E Bolton 1, D L Morris 1
PMCID: PMC2363200  PMID: 10638985

Abstract

Endogenous histamine has been shown to effect growth mechanisms in experimental mammary carcinomas via H2 membrane receptors (Cricco et al, 1994). Both H1 and H2 binding sites are present in human mammary glands but only 75% malignant carcinomas express H2 receptors (Lemos et al, 1995). The presence of mast cells around tumour tissue raises questions concerning the source of histamine in breast tumour tissue. While cimetidine, an H2 antagonist, has been shown to influence the presence of tumour infiltrating lymphocytes (TIL) in colorectal cancer (Adams and Morris, 1994, 1997) that was not found to be the case in breast cancer (Ng et al, 1995). In recent studies tumour cell proliferation, as measured by Ki-67 antibody labelling, has been seen as an additional prognostic indicator in breast cancer (Railo et al, 1993, 1997; Ferno, 1998; Schauer et al, 1998). We investigated the possibility that cimetidine may influence tumour proliferation by blocking the growth-promoting effects of histamine. No relationship between preoperative cimetidine administration and tumour cell proliferation was seen overall. A weak correlation was seen between tissue histamine content and mast cell count which was not influenced by cimetidine. Tumour cell proliferation correlated well with other prognostic indicators such as grade and differentiation. © 2000 Cancer Research Campaign

Keywords: histamine, mast cell, proliferation index, Ki-67

Full Text

The Full Text of this article is available as a PDF (104.9 KB).

Selected References

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

  1. Aaltomaa S., Lipponen P., Papinaho S., Kosma V. M. Mast cells in breast cancer. Anticancer Res. 1993 May-Jun;13(3):785–788. [PubMed] [Google Scholar]
  2. Adams W. J., Lawson J. A., Morris D. L. Cimetidine inhibits in vivo growth of human colon cancer and reverses histamine stimulated in vitro and in vivo growth. Gut. 1994 Nov;35(11):1632–1636. doi: 10.1136/gut.35.11.1632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Adams W. J., Morris D. L. Pilot study--cimetidine enhances lymphocyte infiltration of human colorectal carcinoma: results of a small randomized control trial. Cancer. 1997 Jul 1;80(1):15–21. doi: 10.1002/(sici)1097-0142(19970701)80:1<15::aid-cncr3>3.0.co;2-e. [DOI] [PubMed] [Google Scholar]
  4. Bouzubar N., Walker K. J., Griffiths K., Ellis I. O., Elston C. W., Robertson J. F., Blamey R. W., Nicholson R. I. Ki67 immunostaining in primary breast cancer: pathological and clinical associations. Br J Cancer. 1989 Jun;59(6):943–947. doi: 10.1038/bjc.1989.200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Cricco G. P., Davio C. A., Martin G., Engel N., Fitzsimons C. P., Bergoc R. M., Rivera E. S. Histamine as an autocrine growth factor in experimental mammary carcinomas. Agents Actions. 1994 Nov;43(1-2):17–20. doi: 10.1007/BF02005757. [DOI] [PubMed] [Google Scholar]
  7. Davio C. A., Cricco G. P., Martin G., Fitzsimons C. P., Bergoc R. M., Rivera E. S. Effect of histamine on growth and differentiation of the rat mammary gland. Agents Actions. 1994 Jun;41(Spec No):C115–C117. doi: 10.1007/BF02007792. [DOI] [PubMed] [Google Scholar]
  8. Davio C., Baldi A., Mladovan A., Cricco G., Fitzsimons C., Bergoc R., Rivera E. Expression of histamine receptors in different cell lines derived from mammary gland and human breast carcinomas. Inflamm Res. 1995 Apr;44 (Suppl 1):S70–S71. doi: 10.1007/BF01674401. [DOI] [PubMed] [Google Scholar]
  9. Fernö M. Prognostic factors in breast cancer: a brief review. Anticancer Res. 1998 May-Jun;18(3C):2167–2171. [PubMed] [Google Scholar]
  10. Gerdes J., Li L., Schlueter C., Duchrow M., Wohlenberg C., Gerlach C., Stahmer I., Kloth S., Brandt E., Flad H. D. Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol. 1991 Apr;138(4):867–873. [PMC free article] [PubMed] [Google Scholar]
  11. Lemos B., Davio C., Gass H., Gonzalez P., Cricco G., Martin G., Bergoc R., Rivera E. Histamine receptors in human mammary gland, different benign lesions and mammary carcinomas. Inflamm Res. 1995 Apr;44 (Suppl 1):S68–S69. doi: 10.1007/BF01674400. [DOI] [PubMed] [Google Scholar]
  12. Leonardi E., Girlando S., Serio G., Mauri F. A., Perrone G., Scampini S., Dalla Palma P., Barbareschi M. PCNA and Ki67 expression in breast carcinoma: correlations with clinical and biological variables. J Clin Pathol. 1992 May;45(5):416–419. doi: 10.1136/jcp.45.5.416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. McCormick D., Yu C., Hobbs C., Hall P. A. The relevance of antibody concentration to the immunohistological quantification of cell proliferation-associated antigens. Histopathology. 1993 Jun;22(6):543–547. doi: 10.1111/j.1365-2559.1993.tb00174.x. [DOI] [PubMed] [Google Scholar]
  14. Railo M., Lundin J., Haglund C., von Smitten K., von Boguslawsky K., Nordling S. Ki-67, p53, Er-receptors, ploidy and S-phase as prognostic factors in T1 node negative breast cancer. Acta Oncol. 1997;36(4):369–374. doi: 10.3109/02841869709001282. [DOI] [PubMed] [Google Scholar]
  15. Railo M., Nordling S., von Boguslawsky K., Leivonen M., Kyllönen L., von Smitten K. Prognostic value of Ki-67 immunolabelling in primary operable breast cancer. Br J Cancer. 1993 Sep;68(3):579–583. doi: 10.1038/bjc.1993.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Reynolds J. L., Akhter J. A., Magarey C. J., Schwartz P., Adams W. J., Morris D. L. Histamine in human breast cancer. Br J Surg. 1998 Apr;85(4):538–541. doi: 10.1046/j.1365-2168.1998.00625.x. [DOI] [PubMed] [Google Scholar]
  17. Schauer A., Korabiowska M., Kellner S., Schumacher M., Sauer R., Bojar H., Rauschecker H. Grading system for breast cancer. Anticancer Res. 1998 May-Jun;18(3C):2139–2144. [PubMed] [Google Scholar]
  18. Thomas M., Noguchi M., Kitagawa H., Kinoshita K., Miyazaki I. Poor prognostic value of proliferating cell nuclear antigen labelling index in breast carcinoma. J Clin Pathol. 1993 Jun;46(6):525–528. doi: 10.1136/jcp.46.6.525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tubiana M., Courdi A. Cell proliferation kinetics in human solid tumors: relation to probability of metastatic dissemination and long-term survival. Radiother Oncol. 1989 May;15(1):1–18. doi: 10.1016/0167-8140(89)90113-8. [DOI] [PubMed] [Google Scholar]
  20. Veronese S. M., Gambacorta M. Detection of Ki-67 proliferation rate in breast cancer. Correlation with clinical and pathologic features. Am J Clin Pathol. 1991 Jan;95(1):30–34. doi: 10.1093/ajcp/95.1.30. [DOI] [PubMed] [Google Scholar]
  21. Vielh P., Chevillard S., Mosseri V., Donatini B., Magdelenat H. Ki67 index and S-phase fraction in human breast carcinomas. Comparison and correlations with prognostic factors. Am J Clin Pathol. 1990 Dec;94(6):681–686. doi: 10.1093/ajcp/94.6.681. [DOI] [PubMed] [Google Scholar]

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

RESOURCES