18 research outputs found
Immunocytochemical detection of prognostic markers in breast cancer; technical considerations
The value of immunohistochemistry in patients with poorly differentiated adenocarcinomas and undifferentiated carcinomas of unknown primary
Receptors for hormones and growth factors and (onco)-gene amplification in human ovarian cancer
The clinical significance of androgen receptors in breast cancer and their relation to histological and cell biological parameters
To analyse the clinical significance of the presence of androgen receptors (AR) in breast carcinomas, clinical and histological parameters of 153 primary breast carcinomas (median follow-up 46 months) were examined. Oestrogen (ER) and progesterone receptor (PR) levels were determined in cytosol preparations using enzyme immunoassay assays and in cryostat sections by immunohistochemistry. AR and Ki-67 levels were only determined immunohistochemically. Data were analysed by uni- and multivariate models. 94/153 (61%) breast carcinomas were ER+ PR+ AR+, while 14 cases were only positive for AR. All grade III tumours (n = 17) were steroid receptor negative and 14 (76%) of these cases demonstrated high Ki-67 values suggestive of more aggressive behaviour. Strikingly, 14 ductal carcinomas negative for ER and PR were positive for AR. In univariate analysis, AR as well as ER, tumour size, lymph node status, grade and Ki-67 proved to be significant prognostic factors for disease free survival (DFS). Multivariate analysis, however, showed lymph node status, tumour size and ER status to be the only independent prognostic factors for DFS within this model. We conclude that simple histological and cell biological parameters, including AR, can be used to select high- and low-risk patients at the time of primary surgery and can provide valuable information on treatment options
Occurrence of epidermal growth factor receptors in benign and malignant ovarian tumors and normal ovarian tissues: an immunohistochemical study
Epidermal growth factor receptor (EGF-R) was studied with monoclonal antibody 2E9 on 50 ovarian tumors of various histological types and 10 non-tumorous ovarian tissues by immunohistochemistry. Enhanced expression was observed in 26/50 (52%) of the tumors. Only 25 out of 46 epithelial tumors (54%) showed positivity in epithelial tumor cells. Staining was cytoplasmic in all cases. No correlation was established between EGF-R expression and the histological type of the epithelial tumor. Apart from EGF-R expression in tumor cells, low immunoreactivity was also observed in stromal and endothelial cells in both normal and tumorous ovarian tissues. Furthermore in 8/9 specimens containing necrotic areas, EGF-R was noticed in these areas as well. Both of the latter observations may have impact on the evaluation of the prognostic value of EGF-R activity in tumors, when based on EGF-R measurements using biochemical binding studies. We therefore recommend that EGF-R is measured with both methods in studies regarding its clinical value
The urokinase system of plasminogen activation and prognosis in 2780 breast cancer patients
The antigen levels of components of the urokinase-type plasminogen
activator (uPA) system of plasminogen activation are correlated with
prognosis in several types of cancers, including breast cancer. In the
present study involving 2780 patients with primary invasive breast cancer,
we have evaluated the prognostic importance of the four major components
of the uPA system [uPA, the receptor uPAR (CD87), and the inhibitors PAI-1
and PAI-2]. The antigen levels were determined by ELISA in cytosols
prepared from primary breast tumors. The levels of the four factors
significantly correlated with each other; the Spearman rank correlation
coefficients (r(s)) ranged from 0.32 (between PAI-2 and PAI-1 or uPAR) to
0.59 (between uPA and PAI-1). The median duration of follow-up of patients
still alive was 88 months. In the multivariate analyses for relapse-free
survival (RFS) and overall survival (OS), we defined a basic model
including age, menopausal status, tumor size and grade, lymph node status,
adjuvant therapy, and steroid hormone receptor status. uPA, uPAR, PAI-1,
and PAI-2 were considered as categorical variables, each with two cut
points that were established by isotonic regression analysis. Compared
with tumors with low levels, those with intermediate and high levels
showed a relative hazard rate (RHR) and 95% confidence interval (95% CI)
of 1.22 (1.02-1.45) and 1.69 (1.39-2.05) for uPA, and 1.32 (1.14-1.54) and
2.17 (1.74-2.70) for PAI-1, respectively, in multivariate analysis for RFS
in all patients. Compared with tumors with high PAI-2 levels, those with
intermediate and low levels showed a poor RFS with a RHR (95% CI) of 1.30
(1.14-1.48) and 1.76 (1.38-2.24), respectively. Similar results were
obtained in the multivariate analysis for OS in all patients. Furthermore,
uPA and PAI-1 were independent predictive factors of a poor RFS and OS in
node-negative and node-positive patients. PAI-2 also added to the
multivariate models for RFS in node-negative and node-positive patients,
and in the analysis for OS in node-negative patients. uPAR did not further
contribute to any of the multivariate models. A prognostic score was
calculated based on the estimates from the final multivariate model for
RFS. Using this score, the difference between the highest and lowest 10%
risk groups was 66% in the analysis for RFS at 10 years and 61% in the
analysis for OS. Moreover, separate prognostic scores were calculated for
node-negative and node-positive patients. In the 10% highest risk groups,
the proportion of disease-free patients was only 27 +/- 6% and 9 +/- 3% at
10 years for node-negative and node-positive patients, respectively. These
proportions were 86 +/- 4% and 61 +/- 6% for the corresponding 10% lowest
risk groups of relapse. We conclude that several components of the uPA
system are potential predictors of RFS and OS in patients with primary
invasive breast cancer. Knowledge of these factors could be helpful to
assess the individual risk of patients, to select various types of
adjuvant treatment and to identify patients who may benefit from targeted
therapies that are currently being developed
Complete sequencing of TP53 predicts poor response to systemic therapy of advanced breast cancer
TP53 has been implicated in regulation of the cell cycle, DNA repair, and
apoptosis. We studied, in primary breast tumors through direct cDNA
sequencing of exons 2-11, whether TP53 gene mutations can predict response
in patients with advanced disease to either first-line tamoxifen therapy
(202 patients, of whom 55% responded) or up-front (poly)chemotherapy (41
patients, of whom 46% responded). TP53 mutations were detected in 90 of
243 (37%) tumors, and one-fourth of these mutations resulted in a
premature termination of the protein. The mutations were observed in 32%
(65 of 202) of the primary tumors of tamoxifen-treated patients and in 61%
(25 of 41) of the primary tumors of the chemotherapy patients. TP53
mutation was significantly associated with a poor response to tamoxifen
[31% versu