Immunohistochemical detection of receptors, proteases, tumour suppressor proteins and proliferating markers as prognostic indicators for primary breast cancer patients

Objective: We tested whether immunohistochemical detection of oestrogen and progesterone receptor (ER, PR), the oestrogen-dependent protein pS2, the growth hormone receptors p 185(neu) and EGF-R, the tumour suppressor protein p53, the tissue proteases Cathepsin D and Urokinase, and the proliferation marker PCNA are of prognostic relevance in breast cancer patients. Method: Expression of the proteins listed above was evaluated in formalin-fixed and paraffin-embedded sections of 311 primary breast cancer specimens using modified Avidin-Biotin-Complex methods. Results were correlated to clinical and morphological parameters (age, menopausal status, nodal status, tumour size, tumour grade), and clinical course of disease (complete follow-up in 301 women, median observation time 62 months) utilising univariate and multivariate statistical analyses. Results: If univariate analyses and multivariate regression analyses,according to the Cox-model were applied, only Cathepsin D correlated to an elevated risk for recurrence in nodally negative patients (n=135). In nodally positive women (n=161), increasing tumour size, tumour grade, lack of ER and PR, expression of p185(neu), p53, and PCNA indicated a significantly increased relative risk. Conclusions: Immunohistochemistry allows the detection of parameters which may indicate prognosis in subgroup of breast cancer patients.