10 research outputs found
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
Ki-67 staining in benign, borderline, malignant primary and metastatic ovarian tumors: Correlation with steroid receptors, epidermal-growth-factor receptor and cathepsin D
Ki-67 immunoreactivity was studied in relation to immunohistochemically assessed expression of epidermal-growth-factor receptor (EGFR), estrogen receptor (ER) progesterone receptor (PgR) and cytosolic levels of cathepsin D in advanced human ovarian adenocarcinomas, borderline and benign cystadenomas and normal ovaries. A significantly higher number of Ki-67-positive cells were found in metastatic tumors vs. primary adenocarcinomas and in the total group of adenocarcinomas vs. benign/borderline cystadenomas. Cathepsin-D levels were also significantly higher in metastatic tumors than in primary adenocarcinomas, which in turn presented higher levels than were found in normal ovaries. However, no significant difference was observed between cathepsin-D levels in malignant adenocarcinomas and borderline/benign cystadenomas. Immunohistochemically assessed expression of ER and PgR was detected in variable percentages of epithelial tumor cells, and stromal cells were occasionally positive as well. In the group of primary adenocarcinomas, 46% were ER-positive and 34% were PgR-positive, although there was no significant difference between primary and metastatic lesions with respect to ER or PgR expression. Concordance between immunohistochemically assessed ER or PgR data and cytosolic ER and PgR levels measured with enzyme immunoassay was relatively low. EGFR, immunohistochemically assessed with MAb-EGFRI, was positive in 76% of the primary and in 78% of the metastatic adenocarcinomas. A strong positive association was detected between ER and PgR, and EGFR was observed to present a weak positive correlation with Ki-67 and ER. Cathepsin-D levels were not found to be significantly correlated with the expression of ER, PgR, EGFR or Ki-67. © 1994 Wiley-Liss, Inc
The prognostic value of epidermal growth factor receptor, determined by both immunohistochemistry and ligand binding assays, in primary epithelial ovarian cancer: A pilot study
After our previous studies on the incidence of epidermal growth factor receptors (EGF-R) and its relationships with other tumour characteristics in more than 100 ovarian tumours, in the present study we investigated the prognostic value of EGF-R with respect to progression-free survival in 50 patients with primary ovarian cancer and sufficient follow-up (median 26 months, range 10–33 months). EGF-R was measured by both biochemical and two immunohistochemical methods, using two monoclonal antibodies (MAb), in addition to oestrogen receptors (ER) and progesterone receptors (PgR). EGF-R by ligand binding assay and Scatchard analysis were detectable in 63% of the tumours, by immunohistochemistry with MAb 2E9 in 82% and with MAb EGF-R1 in 78% of the tumours. ER-positivity was found in 58% and PgR-positivity in 38% of the patients. The results of the three measurements of EGF-R showed only weak to moderate associations with Spearman rank correlations (Rs) between 0.13 and 0.46. ER and PgR were only weakly correlated (Rs = 0.20) and they showed no significant association with EGF-R status. There was no clear evidence of the existence of correlations between receptor values and FIGO stage and tumour rest. Univariate Cox regression analyses showed that a higher FIGO stage and larger tumour rest were associated with shorter progression-free survival (P = 0.001) while PgR positivity was associated with a longer progression-free survival (P = 0.02). The level of EGF-R (irrespective of the method of determination used) showed a positive correlation with the risk of progression, but this correlation was not statistically significant
Increased transplant-related morbidity and mortality in CMV-seropositive patients despite highly effective prevention of CMV disease after allogeneic T-cell-depleted stem cell transplantation
We evaluated the efficacy, toxicity, and outcome of preemptive ganciclovir
(GCV) therapy in 80 cytomegalovirus (CMV)-seropositive patients
allografted between 1991 and 1996 and compared their outcome to 35
seronegative patients allografted during the same period. Both cohorts
were comparable with respect to diagnosis and distribution of high- versus
standard-risk patients. All patients received a stem cell graft from an
HLA-identical sibling donor, and grafts were partially depleted of T cells
in 109 patients. Patients were monitored for CMV antigenemia by leukocyte
expression of the CMV-pp65 antigen. Fifty-two periods of CMV reactivation
occurring in 30 patients were treated preemptively with GCV. A favorable
response was observed in 48 of 50 periods, and only 2 patients developed
CMV disease: 1 with esophagitis and 1 with pneumonia. Ten of 30 treated
patients developed GCV-related neutropenia (less than 0.5 x 10(9)/L),
which was associated with a high bilirubin at the start of GCV therapy.
Overall survival at 5 years was 64% in the CMV-seronegative cohort and 40%
in the CMV-seropositive cohort (P =.01). Increased treatment-related
mortality accounted for inferior survival. CMV seropositivity proved an
independent risk factor for developing acute graft-versus-host disease,
and acute graft-versus-host disease predicted for higher treatment-related
mortality and worse overall survival in a time-dependent analysis. We
conclude that, although CMV disease can effectively be prevented by
preemptive GCV therapy, CMV seropositivity remains a strong adverse risk
factor for survival following partial T-cell-depleted allogeneic stem cell
transplantation