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