F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología
Abstract
S100P - low molecular weight acidic protein
has been shown to be involved in processes of
proliferation, survival, angiogenesis, multidrug
resistance and metastasis in various human
malignancies. In breast cancer, S100P expression is
associated with immortalization of neoplastic cells and
aggressive tumour behaviour, indicating that this protein
may have adverse prognostic value. We analyzed nuclear
and cytoplasmic expression of S100P in 85 stage II
breast cancer patients with a median follow up of 17
years. Immunohistochemical reactions were performed
on paraffin sections of primary tumours, using
monoclonal antibodies against S100P. We also studied
prognostic value of S100P mRNA expression using the
KM plotter which assessed the effect of 22,277 genes on
survival in 2422 breast cancer patients. Moreover, the
relationship was examined between expression of S100P
in cells of four breast cancer cell lines and their
sensitivity to the 11 most frequently applied cytotoxic
drugs. Univariate and multivariate analyses showed that
higher expression of nuclear S100P (S100Pn) was
typical for cases of a shorter overall survival and
disease-free time. KM plotter analysis showed that
elevated S100P expression was specific for cases of a
relapse-free survival and distant metastases-free
survival. No relationship could be documented between
expression of S100P and sensitivity of breast cancer
cells to cytostatic drugs. We demonstrated that a high
S100Pn expression level was associated with poor
survival in early stage breast cancer patients. Since
preliminary data indicated that expression of S100P was
up-regulated by activation of glucocorticoid receptor and
several agents manifested potential to activate or inhibit
S100P promoter activity, this protein might become a
therapy target and warrants further studies with respect
to its prognostic, predictive and potentially therapeutic
value