K Friese

Technische Universität München, München, Bavaria, Germany

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Publications (835)1467.42 Total impact

  • A Kölbl · F Liesche · U Jeschke · K Friese · U Andergassen

    No preview · Article · Sep 2014 · Geburtshilfe und Frauenheilkunde

  • No preview · Article · Sep 2014 · Geburtshilfe und Frauenheilkunde
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    ABSTRACT: Ovarian granulosa cell tumors (GCTs) are thought to arise from cells of the ovarian follicle and comprise a rare entity of ovarian masses. We recently identified the G-protein-coupled estrogen receptor (GPER/GPR30) to be present in granulosa cells, to be regulated by gonadotropins in epithelial ovarian cancer and to be differentially expressed throughout folliculogenesis. Thus, supposing a possible role of GPER in GCTs, this study aimed to analyze GPER in GCTs. GPER immunoreactivity in GCTs (n = 26; n (primary diagnosis) = 15, n (recurrence) = 11) was studied and correlated with the main clinicopathological variables. Positive GPER staining was identified in 53.8% (14/26) of GCTs and there was no significant relation of GPER with tumor size or lymph node status. Those cases presenting with strong GPER intensity at primary diagnosis showed a significant reduced overall survival (p = 0.002). Due to the fact that GPER is regulated by estrogens, as well as gonadotropins, GPER may also be affected by endocrine therapies applied to GCT patients. Moreover, with our data supposing GPER to be associated with GCT prognosis, GPER might be considered as a possible confounder when assessing the efficacy of hormone-based therapeutic approaches in GCTs.
    Full-text · Article · Aug 2014 · International Journal of Molecular Sciences
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    ABSTRACT: Purpose: Ovarian carcinoma is the third most common gynecological cancer and only short recurrence-free survival and overall survival times are achieved. The role of the estrogen receptor expression is well studied in breast cancer and breast cancer cell lines. Patients with positive estrogen receptor expression have a lower risk for recurrence and a better overall survival. Previous studies have shown that ESR1 methylation influences ovarian cancer development and might thus play a role regarding prognosis of ovarian carcinoma. Methods: A total of 75 patients were identified that were treated for ovarian carcinoma by debulking surgery and adjuvant standard chemotherapy. Isolation and bisulfite treatment of genomic DNA from serial sections of surgically resected ovarian carcinoma tissue was performed using commercially available kits. For the detection of methylated ESR1 promoter sequences, real-time methylation-specific PCR was used. Results: Promoter methylation did not show a correlation between clinical-pathological data for all patients. However, within the subgroup of low-grade ovarian carcinoma patients and patients with an ovarian tumor of low malignant potential methylation of the ESR1 promoter inversely correlated with survival (p = 0.031). Conclusions: Although small numbers of ovarian carcinoma patients were analyzed, methylation status might be useful as a prognostic marker within the subgroup of low-grade ovarian carcinoma patients. Further studies should investigate a larger cohort and also address the use of demethylation agents with respect to improve patient's prognosis in this subgroup of ovarian carcinoma patients.
    No preview · Article · Jun 2014 · Journal of Cancer Research and Clinical Oncology
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    ABSTRACT: Circulating tumor cells (CTCs) have been shown to predict reduced survival outcomes in metastatic breast cancer. CTCs were analyzed in 2026 patients with early breast cancer before adjuvant chemotherapy and in 1492 patients after chemotherapy using the CellSearch System. After immuno-magnetic enrichment for cells expressing the epithelial-cell adhesion molecule, CTCs were defined as nucleated cells expressing cytokeratin and lacking CD45. The patients were followed for a median of 35 months (range = 0-54). Kaplan-Meier analyses and the log-rank test were used for survival analyses. All statistical tests were two-sided. Before chemotherapy, CTCs were detected in 21.5% of patients (n = 435 of 2026), with 19.6% (n = 136 of 692) of node-negative and 22.4% (n = 299 of 1334) of node-positive patients showing CTCs (P < .001). No association was found with tumor size, grading, or hormone receptor status. After chemotherapy, 22.1% of patients (n = 330 of 1493) were CTC positive. The presence of CTCs was associated with poor disease-free survival (DFS; P < .0001), distant DFS (P < .001), breast cancer-specific survival (P = .008), and overall survival (OS; P = .0002). CTCs were confirmed as independent prognostic markers in multivariable analysis for DFS (hazard ratio [HR] = 2.11; 95% confidence interval [CI] = 1.49 to 2.99; P < .0001) and OS (HR = 2.18; 95% CI = 1.32 to 3.59; P = .002). The prognosis was worst in patients with at least five CTCs per 30mL blood (DFS: HR = 4.51, 95% CI = 2.59 to 7.86; OS: HR = 3.60, 95% CI = 1.56 to 8.45). The presence of persisting CTCs after chemotherapy showed a negative influence on DFS (HR = 1.12; 95% CI = 1.02 to 1.25; P = .02) and on OS (HR = 1.16; 95% CI = 0.99 to 1.37; P = .06) CONCLUSIONS: These results suggest the independent prognostic relevance of CTCs both before and after adjuvant chemotherapy in a large prospective trial of patients with primary breast cancer.
    Full-text · Article · May 2014 · Journal of the National Cancer Institute
  • U Andergassen · A Kölbl · RA Hiller · U Jeschke · K Friese

    No preview · Article · May 2014 · Senologie - Zeitschrift für Mammadiagnostik und -therapie

  • No preview · Article · May 2014 · Senologie - Zeitschrift für Mammadiagnostik und -therapie
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    ABSTRACT: Background. Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
    Full-text · Article · Apr 2014 · BioMed Research International
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    ABSTRACT: Background: Evidence is accumulating that circulating tumor cells (CTC) out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC). Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and methods: We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA) and a manual immunocytochemistry (MICC). The cut-off value for positivity was ≥1 CTC. Results: The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972) and 20.6% (247 out of 1198) of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598) and 16.6% (177 out of 1066) of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P = 0.749), while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P < 0.001). Conclusion: Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.
    Full-text · Article · Apr 2014
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    ABSTRACT: Background The invoicing of inpatient cases in Germany is carried out via the German diagnosis-related groups (G-DRG) system which is annually adapted corresponding to changes in costs and provision of services. In this process the DRG Institute (InEK, Institute for the Remuneration System in Hospitals) of the self-governing partners evaluates the data of the hospital services. The DRG-InEK is therefore entrusted to annually make the DRG calculations corresponding to the available data and to develop the system further. Cooperation from the hospital services is therefore an indispensible prerequisite. Aim Within the framework of the DRG evaluation project for 2012 the Deutsche Gesellschaft für Gynäkologie und Geburtshilfe (DGGG, German Society for Gynecology and Obstetrics) decided to take on the responsibility of ensuring a greater distributional justice in the discipline of gynecology and obstetrics. Material and methods On behalf of the DGGG from February 2012 to July 2012 gynecology departments in German clinics were contacted and asked if they were willing to participate in this project. In addition to financial participation they were asked to deliver data on costs and services provided in 2011 corresponding to the data provided to the InEK by the hospitals. Within the framework of evaluation of the collated data examples of underfinancing in the DRG system were uncovered, disproportionately compensated DRGs were identified and corresponding proposals for a fairer redistribution were submitted to the InEK. Additionally, alterations to the codes of the operations and procedures key (OPS) and the International Statistical Classification of Diseases and Related Health Problems (ICD) were necessary in order to be able to more easily depict the severity and assignment of cases to defined DRGs. Results These proposals were passed on to the Deutsche Institut für Medizinische Dokumentation und Information (DIMDI, German Institute for Medical Documentation and Information). A decision on the implementation of these adjustment proposals for the G-DRG system was made by the InEK in September 2013 and the majority of proposals were accepted completely or in modified form. The discipline has clearly profited from a fairer distribution and also in the sense of additional revenue. Further proposals which have partly arisen from the implementation and suggestions which could not be dealt with due to the lack of time will be resubmitted next year by the DGGG. Conclusion The financial pressure on gynecological obstetric clinics will not be reduced by the further development of the G-DRG system.
    No preview · Article · Apr 2014 · Der Gynäkologe
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    ABSTRACT: Lipocalins are a large protein family with only little sequence homology but highly conserved structural similarity. Many lipocalins play crucial roles in the generation of epithelial cancer, influencing pathways which regulate cell motility, cell differentiation and neovascularisation. Thereby they can be used as biomarkers of cancer, in most cases for a rather good prognosis. Glycodelin is a lipocalin existing in three isoforms which differ only by glycosylation, but which have different functions. In breast cancer, glycodelin A is known to contribute to a more differentiated cell morphology and is a biomarker for a favourable prognosis, but also plays a role in angiogenesis. Glycodelin A is a useful prognostic marker as it can be detected in serum samples, but is also a target for therapeutical interventions.
    No preview · Article · Mar 2014 · Anticancer research

  • No preview · Article · Mar 2014 · Journal of Reproductive Immunology
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    ABSTRACT: Objectives An association between malnutrition and poor patient outcome has been established in various medical fields, but there is a general lack of data on the prevalence of malnutrition among gynecologic patients. Therefore an assessment of malnutrition is needed to detect malnourished patients in gynecology and initiate nutritional therapy if needed. Study design: Between 2011 and 2012 at our gynecologic department of a German university hospital, 397 patients were evaluated regarding the risk of malnutrition and occurrence of complications during the time of hospitalization. The Nutritional Risk Screening (NRS) 2002 system was used to estimate the risk level for malnutrition. Of the 397 patients, 336 received surgery and 61 were treated conservatively. Patients were included independently of surgical intervention or age. The parameters for the clinical outcome were complications and time of hospitalization. Results A severe risk of malnutrition was diagnosed in 142 patients (35.8%) according to an NRS score of ≥ 3. Furthermore, a significantly higher complication rate among those patients who were at risk for malnutrition (NRS 1-2) (7.8%) or who were malnourished (NRS ≥ 3) (22.8%) was found (p < 0.001 χ2). Regarding the length of stay (LOS) in hospital, the medial hospitalisation time increased from 7 to 10 days when patients were malnourished (NRS score≥ 3) (p <0.001). Conclusions Malnutrition occurs frequently among gynecologic patients. Adequate perioperative nutritional supportive therapy should be considered in malnourished patients to improve their clinical outcome.
    Preview · Article · Mar 2014 · European journal of obstetrics, gynecology, and reproductive biology

  • No preview · Article · Mar 2014 · Journal of Reproductive Immunology
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    ABSTRACT: Background/Aim: Estrogen receptor-alpha is usually expressed in normal cervical tissue, but its presence is decreased or absent in invasive cervical cancer indicating that its expression is lost during development of invasive cervical cancer. The aim of the present study was to investigate ESR1 promoter methylation in cervical cancer and correlate methylation status with clinico-pathological parameters. Fifty patients treated for cervical cancer were included in the study. Isolation and bisulfite treatment of genomic DNA from cervical cancer tissue was performed by commercially-available kits. Methylated ESR1 promoter sequences were detected by quantitative real-time methylation-specific PCR. Methylation status did not present differences regarding age at-diagnosis, FIGO stage, grade, BMI and overall survival for all patients, but within the subgroup of non-keratinizing squamous cell cancer methylation status correlated with grading (p=0.047). Methylation of the ESR1 promoter does not seem to be of any prognostic relevance, but is associated with higher tumor grading of cervical cancer patients.
    No preview · Article · Feb 2014 · Anticancer research
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    ABSTRACT: Disseminated tumour cells (DTCs) in the bone marrow derive from many primary tumours, such as breast cancer. Their mere existence hints to present or future metastasis and implicates a worse prognosis for the patient. DTCs may possess different characteristics in comparison to the primary tumour due to events like Epithelial-Mesenchymal-Transition. Therefore, these cells might be able to survive chemotherapy and cause relapses of the disease at a later point. We aimed to detect and further characterise DTCs by an immunostaining approach with three different antigen markers (Her-2, MUC-1 and TF, also known as CD 176). For that reason, bone marrow of 41 breast cancer patients was obtained during surgery; DTCs were enriched by density gradient centrifugation and cytospins were prepared. After fixation, immunofluorescent double-stainings were carried out with antibodies against CD176 in combination with HER-2 or MUC-1. Cells co-expressing two antigens were found in all staining combinations (Her-2 and CD176: 46.14%; MUC-1 and CD176: 18.15% of all cases). Cells that stained for a single antigen only were also found (Her-2: 36.86%; MUC-1: 34.45%; CD176: 29.65% of all cases). Significant correlations between the stainings of all markers could be shown (p⟨0,001). In conclusion, Thomsen-Friedenreich Antigen (TF, CD176) is a promising marker in combination with the established marker Her-2 and other markers like MUC-1. These results may serve as a basis for future DTC detection routines and help to individualize medical treatment, reducing side effects and increasing the efficiency of the therapy.
    No preview · Article · Jan 2014 · Histology and histopathology
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    ABSTRACT: Breast reconstruction with salpingo-oophorectomy can easily be performed in patients with genetic mutations increasing the risk for mammary and ovarian carcinoma. However, many patients are skeptical about having several surgeries, as they may result in additional anesthesiological risks as well as multiple visible scars. Therefore, the purpose of this study was to evaluate the feasibility of prophylactic mastectomy and breast reconstruction combined with simultaneous transmammary salpingo-oophorectomy for BRCA carriers. Of the six patients (1 %) who chose prophylactic mastectomy with salpingo-oophorectomy at our hospital four patients had BRCA-1 mutations, one patient had a BRCA-2 mutation and one patient had a family inheritance pattern with no mutations. All patients chose to reduce their risk for mammary and ovarian cancer by undergoing bilateral mastectomy and bilateral salpingo-oophorectomy. Prophylactic mastectomy with immediate reconstruction was performed, followed by bilateral salpingo-oophorectomy with a procedure that relies on transmammary access and reduces the number of necessary surgeries without compromising cosmetic results, surgical risks and operating time. The mean age of the patients was 46.7 ± 1.8 years (SD). The mean operative time was 190.2 ± 13.7 min. No complications were observed during the operations. The mean intra-operative loss of blood was 363.3 ± 77.9 ml. The operative method was successful in all six cases and was performed with no complications. All of the patients were satisfied with the cosmetic results. In conclusion, prophylactic mastectomy and breast reconstruction combined with simultaneous laparoscopic salpingo-oophorectomy via transmammary access is feasible, easy to perform and provides an intriguing and novel approach to female BRCA carriers who desire operative prophylactic measures in one surgical session with no visible abdominal scars and no additional risks and complications.
    No preview · Article · Jan 2014 · Archives of Gynecology
  • W. Kirschner · I. Mylonas · K. Friese
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    ABSTRACT: Although preterm birth rates are showing a downward trend or are at least remaining constant in some developed countries, preterm delivery remains a major challenge in obstetrics. In Germany the current preterm birth rate is 8 % and 9 % of newborns are born preterm. Thus, Germany is still the country with the highest rates in Europe. Epidemiological knowledge on the risk factors of preterm birth is quite satisfactory even though there are some grey areas that need to be addressed; however, currently there is no program worldwide which reduces the number of preterm deliveries in the total population of pregnant women, while reductions can be seen in several study groups. This paper outlines the essential requirements for the design and implementation of targeted interventions and gives two examples. Additionally, for targeted interventions a revision of the current risk classification of pregnant women is necessary to identify women at actual risk as it is totally unusable for practical interventions by gynecologists. Furthermore, a substantial promotion of healthcare research and respective evaluations are necessary. When looking at the risk factors of nutrition and body weight in the mid-term and long-term, the prevention of preterm birth also has to be more intensively organized from preconception aspects.
    No preview · Article · Jan 2014
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    ABSTRACT: Knowledge on immunosuppressive factors in the pathogenesis of endometrial cancer is scarce. The aim of this study was to assess Glycodelin (Gd) and its immunosuppressive isoform Glycodelin A (GdA) in endometrial cancer tissue and to analyze its impact on clinical and pathological features and patient outcome. 292 patients diagnosed and treated for endometrial cancer were included. Patient characteristics, histology and follow-up data were available. Gd and GdA was determined by immunohistochemistry and in situ hybridization was performed for Gd mRNA. Endometrial cancer shows intermediate (52.2%) or high (20.6%) expression for Gd in 72.8%, and GdA in 71.6% (intermediate 62.6%, high 9.0%) of all cases. The glycolysation-dependent staining of GdA is tumour specific and correlates with the peptide-specific Gd staining though neither of the two is associated with estrogen receptor, progesterone receptor or clinic-pathological features. Also Gd protein positively correlates with Gd mRNA as quantified by in situ hybridization. Gd positive cases have a favourable prognosis (p = 0.039), while GdA positive patients have a poor outcome (p = 0.003). Cox-regression analysis proofed GdA to be an independent prognostic marker for patient survival (p = 0.002), besides tumour stage, grade and the concomitant diagnosis of hypertension. Gd and GdA are commonly expressed in endometrial cancer tissue and seem to be of relevance in tumourigenesis. They differ not only in glycolysation but also in their biological activity, since only GdA holds prognostic significance for a poor overall survival in endometrial cancer patients. This finding might be explained by GdAs immunosuppressive capacity.
    No preview · Article · Dec 2013 · BMC Cancer
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    ABSTRACT: Breast cancer is still the most frequent cause of cancer-related death in women worldwide. Often death is not caused only by the primary tumour itself, but also by metastatic lesions. Today it is largely accepted, that these remote metastases arise out of cells, which detach from the primary tumour, enter circulation, settle down at secondary sites in the body and are called Circulating Tumour Cells (CTCs). The occurrence of such minimal residual diseases in the blood of breast cancer patients is mostly linked to a worse prognosis for therapy outcome and overall survival. Due to their very low frequency, the detection of CTCs is, still a technical challenge. RT-qPCR as a highly sensitive method could be an approach for CTC-detection from peripheral blood of breast cancer patients. This assumption is based on the fact that CTCs are of epithelial origin and therefore express a different gene panel than surrounding blood cells. For the technical approach it is necessary to identify appropriate marker genes and to correlate their gene expression levels to the number of tumour cells within a sample in an in vitro approach. After that, samples from adjuvant and metastatic patients can be analysed. This approach may lead to new concepts in diagnosis and treatment.
    Full-text · Article · Dec 2013 · Cancers

Publication Stats

6k Citations
1,467.42 Total Impact Points

Institutions

  • 2005-2015
    • Technische Universität München
      München, Bavaria, Germany
    • Karl-Franzens-Universität Graz
      Gratz, Styria, Austria
    • Robert-Bosch Krankenhaus
      Stuttgart, Baden-Württemberg, Germany
  • 2003-2015
    • Ludwig-Maximilians-University of Munich
      • Clinic and Polyclinic for Obstetrics and Gynecology
      München, Bavaria, Germany
    • University Hospital München
      München, Bavaria, Germany
  • 2013
    • Universitätsklinikum Erlangen
      Erlangen, Bavaria, Germany
  • 2012
    • University of Ioannina
      • Division of Obstetrics-Gynaecology
      Yannina, Epirus, Greece
    • Klinikum Stuttgart
      Stuttgart, Baden-Württemberg, Germany
  • 2010
    • University of Cologne
      Köln, North Rhine-Westphalia, Germany
    • Otto-Friedrich-Universität Bamberg
      Bamberg, Bavaria, Germany
  • 1998-2010
    • University of Rostock
      • Faculty of Medicine
      Rostock, Mecklenburg-Vorpommern, Germany
  • 2009
    • Heinrich-Heine-Universität Düsseldorf
      Düsseldorf, North Rhine-Westphalia, Germany
  • 2008
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • Department of Clinical Chemistry
      Amsterdamo, North Holland, Netherlands
  • 2007
    • Charité Universitätsmedizin Berlin
      • Department of Obstetrics
      Berlin, Land Berlin, Germany