[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: There is partially conflicting evidence on the influence of the steroid hormones estrogen (E) and progesterone (P) on the development of ovarian cancer (OC). The aim of this study was to assess the expression of the receptor isoforms ER-alpha/-beta and PR-A/-B in OC tissue and to analyze its impact on clinical and pathological features and patient outcome. METHODS: 155 OC patients were included who had been diagnosed and treated between 1990 and 2002. Patient characteristics, histology and follow-up data were available. ER-alpha/-beta and PR-A/-B expression were determined by immunohistochemistry. RESULTS: OC tissue was positive for ER-alpha/-beta in 31.4% and 60.1% and PR-A/-B in 36.2% and 33.8%, respectively. We identified significant differences in ER-beta expression related to the histological subtype (p=0.041), stage (p=0.002) and grade (p=0.011) as well as PR-A and tumor stage (p=0.03). Interestingly, median receptor expression for ER-alpha and PR-A/-B was significantly higher in G1 vs. G2 OC. Kaplan Meier analysis revealed a good prognosis for ER-alpha positive (p=0.039) and PR-B positive (p<0.001) OC. In contrast, ER-beta negative OC had a favorable outcome (p=0.049). Besides tumor grade and stage, Cox-regression analysis showed PR-B to be an independent prognostic marker for patient survival (p=0.009, 95% CI 0.251-0.823, HR 0.455). CONCLUSION: ER-alpha/-beta and PR-A/-B are frequently expressed in OC with a certain variability relating to histological subtype, grade and stage. Univariate analysis indicated a favorable outcome for ER-alpha positive and PR-B positive OC, while multivariate analysis showed PR-B to be the only independent prognostic marker for patient survival. In conclusion, ER and PR receptors may be useful targets for a more individualized OC therapy.
BMC Cancer 11/2012; 12(1):553. · 3.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: The evaluation of breast implants for rupture is currently the domain of ultrasound and MRI, while mammography is of very limited diagnostic value. Recently, specific visualisation of silicone has become feasible using dual-energy CT. Our objective was to evaluate whether it is feasible to identify silicone in breast implants by dual-energy CT and to reliably diagnose or rule out ruptures. METHODS: Seven silicone breast implant specimens were examined on dual-source CT at 100- and 140-kV tube potential with a 0.8-mm tin filter (collimation 128 × 0.6 mm, current-time products 165 and 140 mAsref with modulation, rotation time 0.28 s, pitch 0.55). Two patients scheduled for implant removal or replacement were examined with identical parameters. RESULTS: The silicone of the implant specimens showed a strong dual-energy signal. In one patient, both implants were intact, while a rupture was identified in the other patient. Ultrasound, MRI, surgical findings and histology confirmed the dual-energy CT diagnosis. CONCLUSION: Dual-energy CT may serve as an alternative technique for speedy evaluation of silicone breast implants. Specific clinical studies are required to determine the diagnostic accuracy and define indications for this technique. KEY POINTS: • Dual-energy CT makes it possible to visualise silicone in breast implants. • Silicone provides a strong photoelectric effect that can be detected. • Initial experience suggests that implant ruptures can be identified or ruled out.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Glycodelin is a cell surface glycoprotein offering a unique gender specific carbohydrate configuration. Sialylated carbohydrate structures, which are unusual for mammals, characterize Glycodelin isolated from amniotic fluid (Glycodelin A, GdA). Glycodelin in general exerts multiple, partly opposing functions ranging from immunosuppression to cell differentiation. As these markedly influence tumorigenesis, this study aimed to clarify whether expression of different Glycodelin isoforms is related to clinicopathological characteristics and prognosis of ovarian cancer patients. Further the use of Glycodelin as a serum marker in benign and malignant ovarian diseases was evaluated. METHODS: Ovarian cancer specimens (n = 152) were stained for Glycodelin with carbohydrate and peptide specific antibodies. Associations between Glycodelin expression and histological grading, FIGO stage as well as patient's prognosis were examined. Glycodelin was correlated to expression of gonadotropin receptors and mucin-1, which are discussed as ovarian cancer tissue markers. In addition, Glycodelin serum concentrations were analyzed in patients suffering from benign (n = 73) or malignant (n = 38) ovarian neoplasias. RESULTS: Glycodelin A was found to be an independent prognostic marker for poor prognosis in advanced ovarian cancer patients. GdA staining correlated with gonadotropin receptor (FSHR and LHCGR) and with hCG expression. Gd expression showed a positive correlation with a tumour-associated epitope of mucin 1 (TA-MUC1). Further, compared to ovarian cancer, serum Gd was increased in patients with benign ovarian tumors. CONCLUSION: Glycodelin A might be related to tumor aggressiveness and poor clinical outcome in advanced epithelial ovarian cancer. Glycodelin serum levels found in patients suffering from benign ovarian tumors, might contribute to a more global attenuation during progression of these precursor lesions.
[Show abstract][Hide abstract] ABSTRACT: Non-steroidal nuclear receptors play a major role in breast cancer development. A correlation among, and possible prognostic function of, the members of the nuclear receptor superfamily has been discussed controversially over the years. Hence, we conducted a quantification of the different expression levels of the thyroid receptor (TR), retinoid X receptor (RXR), peroxisome proliferator-activated receptor (PPAR) and vitamin D receptor (VDR) in malignant breast tumour tissue samples. Patients diagnosed and treated for breast cancer between 1990 and 2000 were included. Receptor expression was detected by immunohistochemical staining. Correlation analyses for the expression of the receptors were performed for the clinical and histopathological data. The paraffin-embedded tissue from 82 breast cancer patients was available. The different steroid receptors showed varying results when correlated with known histopathological markers. TRα2 demonstrated the most significant correlations with steroid hormone receptors. Significant correlations between the major isoforms of TR, and between RXR, PPAR and VDR, were demonstrated in the patient sample. The immunohistochemical association of these receptors may provide the first proof of an interaction on the molecular level. This assumption awaits confirmation in studies with larger cohorts.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the diagnostic efficacy of backscattering intensity measurements in optical coherence tomography in identifying different grades of cervical intraepithelial dysplasia.
OCT images were taken from 153 unsuspicious and suspicious areas of 30 fresh conisation and hysterectomy specimens, evaluated by two blinded investigators using a six-grade classification (normal, inflammation, CIN1, CIN2, CIN3, squamous carcinoma) and later compared to the corresponding histology. Differences between judgments based on either the histology or the OCT images were investigated employing Correspondence Analysis (CA). Further, we explored the extent as to which backscattering intensity profiles of OCT images contained the essential information required for a reliable and valid diagnosis, using Linear Discriminant Analysis (LDA).
The CA of histology- and OCT-based judgments suggests that the diagnostic process may be characterized in terms of two stochastically independent underlying ("latent") variables, the first of them reflecting the definiteness with which CIN classes are identified, the second reflecting a bias towards diagnosing inflammation on the side of the OCT-based judgments. This finding is supported by the results of LDAs, where histology and OCT categorizations differ in particular with respect to the positions of inflammation and CIN1. Possibly, a second canonical variable has to be assumed accounting for the evaluation of carcinoma.
The systematic differences between histology-based and OCT-based diagnoses suggest that the use of available information is influenced by perceptual and/or cognitive biases. Apart from this it seems that the profiles appear to provide a remarkably large amount of information determining the main course of the diagnostic process.
Lasers in Surgery and Medicine 09/2012; 44(1):11-9. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The differential reaction of cytotrophoblast and syncytiotrophoblast towards infection with listeria monocytogenes (LM) is pivotal to its pathogenicity. In this study we tested the cytokine signature upon infection with listeria monocytogenes (LM) in an in vitro model.
We compared two related trophoblastic cell lines (AC-1M32 and ACH1P). The cell line ACH1P showed syncytium formation, whereas AC-1M32 did not fuse, as demonstrated with immunfluorescence E-Cadherin staining. In a Multi-Analyte ELISArray we tested for concentrations of TNFα, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17A, IL-8, MCP1, MIP-1a, MIP-1b, MDC, Eotaxin, IFNγ, G-CSF, TGFβ1 after 8 and 24 hours.
Compared to unstimulated cells, the syncytial cell line ACH1P showed a significant induction of Interleukin-6 (IL-6), Monocyte Chemotactic Protein-1 (MCP-1) and transforming growth factor β-1 (TGFβ1). Incubating AC-1M32 with LM, however, showed significantly reduced IL-6 levels and a massively increased (~300fold) TGFβ1 secretion compared to unstimulated controls.
A functional anti-LM immune response was only induced by the syncytium-forming cell line ACH1P. Using the two sister cell lines AC-1M32 and ACH1P in an in vitro LM-stimulation assay might facilitate research in the area of placental listeria infection.
American Journal Of Reproductive Immunology 08/2012; 68(5):387-91. · 3.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer.
The ADEBAR trial was a multicenter phase III trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4× epirubicin (90 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 3 weeks (q3w), followed by 4× docetaxel (100 mg/m(2)) q3w (EC-Doc arm), or 6× epirubicin (60 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1 and 8 and cyclophosphamide (75 mg/m(2)) on days 1-14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility.
Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009).
The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy.
Breast Care 08/2012; 7(4):289-95. · 0.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Variations in cytokine and immune mediator expression patterns in amniotic fluid due to gestational age, maternal age and fetal gender were investigated.
Amniotic fluid samples were obtained from 192 women, 82 with a mid-trimester amniocentesis (median gestational age 17 weeks) and 110 with a caesarean section not in labor (median gestational age 39 weeks). Amniotic fluid was screened by commercial ELISAs for the TH1/TH2/TH17 cytokines and immune mediators IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF alpha, GRO-alpha, MIP1alpha, MIP1beta, Histone, and IP10. Analysis was by Bonferroni correction for multiple comparisons. None of the 15 examined cytokines revealed any differences in expression patterns regarding fetal gender. Significant differences were found in IL-4, IL-10, IL-12, TNF- alpha, GRO-alpha and MIP1-beta with respect to gestational age and in GRO-alpha regarding maternal age.
Cytokines utilized as biomarkers in the diagnosis of intrauterine infections are not influenced in their expression pattern by fetal gender but may vary with respect to maternal age and gestational age.
[Show abstract][Hide abstract] ABSTRACT: The fungal drug cordycepin (3-deoxyadenosine) is known to exert anti-tumor activities, preferentially by interfering with RNA synthesis. We have investigated the effect of cordycepin on human breast epithelial cell lines, ranging from non-malignant MCF10A cells to highly de-differentiated MDA-MB-435 cancer cells. Treatment of human breast cancer cells with cordycepin caused either apoptosis or persistent cell cycle arrest that was associated with reduced clonal growth of cordycepin-treated breast cancer cells. Highly de-differentiated breast cancer cell lines, such as MDA-MB-231 and MDA-MB-435, reacted more sensitive to cordycepin than less aggressive breast cancer cell lines (MCF7, T47D) or non-malignant breast epithelial cells (MCF10A), which poorly reacted to cordycepin. In cordycepin-sensitive breast cancer cells, a marked induction of the DNA damage response (DDR), including the phosphorylation of ATM, ATR, and histone γH2AX could be observed. These data indicate that cordycepin, which was believed to cause cancer cell death by inhibition of RNA synthesis, induces DNA double strand breaks in breast cancer cells. The genotoxic effect of cordycepin on breast cancer cells indicates a new mechanism of cordycepin-induced cancer cell death, and its activity against highly undifferentiated breast cancer cells provides a new perspective of how cordycepin may be used in the treatment of advanced breast cancer.
Investigational New Drugs 07/2012; 30(5):1917-25. · 3.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Corticotropin-releasing hormone (CRH) and its receptors are expressed in human placenta. Recently, the impaired function of this system has been associated with a number of complications of pregnancy, including pre-eclampsia. The aim of the study was to test the hypothesis that CRH participates in the pathophysiology of pre-eclampsia through the induction of macrophage-mediated apoptosis of extravillous trophoblasts (EVTs). We found that the expression of CRH was increased in the EVT of the placental bed biopsy specimens from pre-eclamptic pregnancies (1.8-fold increase; P < 0.05). In addition, significantly larger numbers of apoptotic EVT were detected in pre-eclamptic placentas compared with normal ones (P < 0.05), and only in pre-eclamptic placentas, decidual macrophages were found to be Fas ligand (FasL)-positive. In vitro studies on the effect of CRH on human macrophages suggested that CRH induced the expression of the FasL protein in human macrophages and potentiated their ability to induce the apoptosis of a Fas-expressing EVT-based hybridoma cell line in co-cultures. These findings demonstrate a possible mechanism by which the aberrant expression of CRH in pre-eclampsia may activate the FasL-positive decidual macrophages, impair the physiological turnover of EVT and eventually disturb placentation.
Molecular Human Reproduction 07/2012; 18(11):535-45. · 4.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the role of the fossa ischioanalis (FI) in functional relations between the levator ani (LA) and gluteus maximus muscles (GM) in healthy female volunteers.
Twenty-three nulliparae were examined. Electromyogramms of LA and GM were simultaneously recorded during voluntary contraction of the pelvic floor muscles (PFM) and at rest in six body positions. The surface areas of LA (LAA), FI (FIA) and GM (GMA) were evaluated using MRI.
Simultaneous LA and GM contractions were electromyographically observed irrespectively of body position in 97.2 %. MRI revealed synchronous movement of all structures: while LAA (-7.4 %) reduced, GMA increased (+6.8 %), FIA changed significantly (+3.4 %).
The LA, FI and GM are morphologically and functionally connected. We recommend considering these structures as the 'LFG-Complex', emphasising the importance of this unit for functional integration of the pelvic floor. The findings of this study may contribute to understanding of urinary continence mechanism and disorders after pelvic floor surgery and obstetrical trauma.
Archives of Gynecology 06/2012; 286(4):931-8. · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Patients with genital prolapse and occult stress urinary incontinence (OSUI) are typically treated with prolapse surgery and anti-incontinence surgery based on either a one-step approach or a two-step approach. The aim of our study was to determine whether anti-incontinence surgery is necessary based on the occurrence of OSUI in a study cohort with a long follow-up period.
Prolapse surgery was performed using a vaginal approach. Preoperatively, a stress test, a pad test and an assessment of the urodynamics were performed with and without prolapse reduction. Over a follow-up period of 2-8 years, the patients with preoperative evidence of OSUI underwent urogynaecological examinations, stress tests and pad tests.
Of 113 patients with preoperative evidence of OSUI, 57 (50.4 %) were followed up for an average of 5.7 years (range 2-8) after prolapse surgery. Of 57 patients, 16 (28.1 %) had objective and/or subjective stress urinary incontinence (SUI) during the follow-up period, but only 3 patients (5.3 %) required subsequent tension-free vaginal tape (TVT) surgery. In 17 of 57 patients (29.8 %), prolapse recurred.
Despite the preoperative evidence of OSUI, the manifestation of SUI rarely occurs, with 28.1 % of patients experiencing SUI over long-term follow-up after vaginal prolapse surgery. Anti-incontinence surgery was necessary in only three cases (5.3 %). These results indicate that with the one-step approach, 54 of 57 patients (94.7 %) would have received prophylactic anti-incontinence surgery unnecessarily. In conclusion, we recommend the two-step approach in the management of vaginal prolapse surgery in patients with OSUI.
International Urogynecology Journal 05/2012; 23(7):851-5. · 2.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Estrogens play a crucial role in maintaining ovarian function. Deregulation of estrogen signals is associated with fertility-impairing disorders. The aim of this study was to investigate whether the G-protein-coupled estrogen receptor (GPER) is present in the human ovary. Additionally, we analyzed the folliculogenesis and ovarian endometriosis in GPER expression. Seventy-nine patients (ovarian endometriosis, n = 26; ovarian pelvic inflammatory disease [PID], n = 10; normal ovaries/endometrium, n = 30/13) were analyzed by immunohistochemistry. Normal ovaries were also assessed by real-time polymerase chain reaction and double immunofluorescence. The most intense expression of GPER was noted in the ovarian surface epithelium. Theca cells and oocytes were also significantly positive. Expression of GPER was more frequent in mature follicles/oocytes than in primordial ones, implying that GPER could be a selector during folliculogenesis. Moreover, GPER was upregulated in ovarian endometriosis and PID. Overexpression of GPER in both inflammation and endometriosis affecting the ovary may prove useful in explaining/predicting the main endometriosis-related symptoms.
[Show abstract][Hide abstract] ABSTRACT: Purpose: Nowadays, most gynaecologists are female and the compatibility of job-related career and family life is an upcoming issue. The working group "Gender and Career" of the German Society for Gynaecology and Obstetrics (DGGG) designed a survey to reflect the present situation with a focus on the compatibility of career and family. Material and Methods: A web-based 74-item survey was filled out by members of the DGGG. In total, there were 1037 replies, 75 % female (n = 775) and 25 % male (n = 261) gynaecologists. Results: 62 % of the female and 80 % of the male respondents had already finished their doctoral theses and 2 % female and 13 % male had finished their PhD. Mean number of children was 1.06 (SD 1.08) in female and 1.68 (SD 1.34) in male gynaecologists. The majority of females desired day care for their children, but only 5 to 13 % of employers offer any day care. 88 % of the female and 72 % of the male physicians think that job-related career and family are not compatible. Conclusion: The majority of female gynaecologists wished to have professional child care, but most employers or other institutions do not offer this. This might be one of the reasons why career and family appear incompatible.
Geburtshilfe und Frauenheilkunde 05/2012; 72(5):403-407. · 0.85 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mucin 1 (MUC1) is a high molecular weight transmembrane glycoprotein with unique properties which is used as a tumour marker in sera of ovarian cancer patients. The common test kit for the cancer antigen 15-3 (CA15-3) is not sufficient for the discrimination between sera from healthy individuals and sera from patients with benign changes of the ovaries. In this study, the newly developed anti-MUC1 antibody PankoMab was tested in normal and patient sera with an ELISA, and the obtained data were compared against data from experiments using the commercial kits for CA15-3 and CA27.29.
Sera of 123 patients diagnosed with benign or malignant changes of the ovaries were obtained before surgery. CA15-3 was analysed with an automated ELISA system (Immulite 2000). CA27.29 was measured with the ST AIA-PACK CA27.29 for the AIA-600II-Analyzer (Tosoh Bioscience, Belgium). The release of MUC1 fragments carrying the TA-MUC1 epitope was analysed with an ELISA using the PankoMab antibody.
Using the already established markers CA15-3 and CA27.29, significant differences between benign and malignant changes of the ovaries were found. The same result was obtained with the newly developed TA-MUC1 test. In contrast to CA15-3 and CA27.29, however, the median of TA-MUC1 was lower in sera from patients with ovarian cancer compared to sera from patients with benign diseases of the ovary. However, sera of patients with benign ovarian diseases had significantly higher TA-MUC1 values compared to sera of healthy individuals. The risk score of TA-MUC1 achieved an area under the curve (AUC) of 78.4% in receiver operating characteristic (ROC) curves and a sensitivity of 37% for the prediction of ovarian disease, at 95% specificity.
In this study we employed an additional marker for MUC1 which recognizes a more tumour-specific MUC1 epitope (TA-MUC1). We obtained results showing significant differences between detection in benign and malignant ovarian diseases. Although the mean MUC1 values were elevated in sera of patients with ovarian cancer compared to values of patients with benign cysts, by using all three test systems, a different result was found by analysing the median TA-MUC1 values. PankoMab could be a useful, additional tool for obtaining conclusive information on the transformation process from benign to malignant state in ovarian tissues.
Anticancer research 05/2012; 32(5):2185-9. · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The carbohydrate molecules Sialyl Lewis X (SLeX), Sialyl Lewis A (SLeA), Lewis Y (LeY) and Thomsen-Friedenreich antigen (TF) are known to mediate the adhesion between tumor cells and endothelium. They are used as serum markers in diagnosis and treatment in a broad spectrum of human carcinomas, but their expression profile and role in the development of cervical cancer remains unclear. The aim of this study was to investigate the expression of SLeX, SLeA, LeY and TF in normal cervical squamous epithelium, cervical dysplasia and cervical cancer. Slides of paraffin-embedded tissue were fixed and incubated with monoclonal antibodies against SLeX, SLeA, LeY and TF. Immunohistochemical staining was evaluated by using a semi-quantitative score (IRS Score). We found a significant difference of SLeA expression in invasive cervical cancer compared to normal epithelium (p=0.006) and all grades of dysplasia (p=0.002). The expression of SLeX in normal epithelium was less intense than in carcinoma in situ (p=0.036). Staining for LeY showed the weakest results of the investigated markers. Significant differences were found when normal epithelium was compared to CIN I (p=0.011), to CIN II (p=0.013) and to invasive cervical cancer (p=0.005). For TF, significant differences were found in normal epithelium compared to CIN I (p=0.011), CIN II (p=0.013) and compared to invasive cervical cancer (p=0.005). This is the first study on the expression of SLeA, SLeX, LeY and TF in normal cervical endothelium, cervical dysplasia, carcinoma in situ and invasive cervical cancer. Further studies and higher numbers are desirable.
Histology and histopathology 04/2012; 27(4):507-14. · 2.28 Impact Factor