IMMUNOCYTOCHEMICAL LOCALIZATION OF FOS PROTEIN IN HUMAN BREAST CANCERS AND ITS RELATIONSHIP TO A SERIES OF PROGNOSTIC MARKERS AND RESPONSE TO ENDOCRINE THERAPY

The nuclear transcription factor Fos is inducible by both steroid hormones and peptide growth factors. It thus forms a potential point of interaction between steroid hormone- and growth factor-directed pathways and may be critical in the subversion of steroid hormone control in breast cancer. In this light, the present study has used immunocytochemistry to demonstrate in clinical primary breast cancer that Fos expression is indeed significantly associated with a failure to respond to endocrine therapy, with preliminary analysis revealing a survival advantage for those patients whose tumours lacked Fos. Sustained elevated levels of Fos expression were significantly associated with further factors, notably peptide growth factors and their receptors (e.g., EGFR, TGF alpha), as well as with the proliferation marker Ki-67, which have been linked previously to endocrine insensitivity in breast cancer. In contrast, there appeared to be a trend for Fos to be absent in those tumours expressing markers of endocrine responsiveness (e.g., oestrogen receptor [ER], and also PR-mediated markers i.e., PR, pS2 or bcl-2). Interestingly, many of these trends were maintained in ER(+) patients, suggesting that Fos may be of importance in directing loss of endocrine sensitivity in ER(+) disease. (C) 1995 Wiley-Liss, Inc.