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BackgroundThe gold standard to evaluate treatment efficacy in oncology clinical trials is Overall Survival (OS). Its utility, however, is limited by the need for long trial duration and large sample sizes. Thus methods such as Progression-Free Survival (PFS) are applied to obtain early OS estimates across clinical trial phases, particularly to decide on further development of new molecular entities. Especially for cancer-immunotherapy, these established methods may be less suitable. Therefore, alternative approaches to obtain early OS estimates are required. In this work, we present a first evaluation of a new method, ΔRisk. ΔRisk uses the ROPRO, a state-of-the-art pan-cancer OS prognostic score, or DeepROPRO to predict OS benefit by measuring the patient’s improvement since baseline.Patients and methodsWe modeled the ΔRisk using Joint Models and tested whether a significant ΔRisk decrease correlated with OS improvement. We studied this hypothesis by comparing classical OS analysis against ΔRisk in a retrospective analysis of 12 real-world data emulated clinical trials, and 3 additional recent phase III immunotherapy clinical trials.ResultsOur new ΔRisk method correlated with the final OS readout in 14 out of 15 clinical trials. The ΔRisk, however, identified the treatment benefit up to seven months earlier than the OS log-rank test. Additionally, in two immunotherapy trials where PFS would have failed as an early OS estimate, the ΔRisk correctly predicted the treatment benefit.ConclusionsWe introduced a new method, ΔRisk, and demonstrated its correlation with OS. In retrospective analysis, ΔRisk is able to identify OS benefit earlier than standard methodology, and we show examples of lung cancer trials, where it maintains its predictive relevance whereas PFS does not correlate with OS. ΔRisk may prove useful for early decision support resulting in reduced need of resources. We also show the potential of ΔRisk as a candidate to define surrogate endpoints. To this purpose, more methodological work and further investigation of treatment-specific performance will be done in the future.

Introduction: Breast cancer (BC) is the most common cancer in women worldwide. Despite screening and information efforts, about 10% of patients present with tumor size T3 or T4 at primary diagnosis. Late presentation is associated with more advanced tumor stage and consecutively with worse survival rates. Objective: This study aimed to evaluate whether patients with a late presentation at primary BC diagnosis differ in their personality from those with early diagnosis. Methods: In this bicentric, observational study, personality traits, positive and negative affectivity, anxiety, spirituality, illness beliefs, and sociodemographic characteristics were assessed in BC patients who presented with T-stages 3 or 4 (late presenters) and T-stages 1 or 2 (controls) at initial diagnosis. Results: Forty patients (20 controls, 20 late presenters) were interviewed. “Late presenters” perceived their disease as long lasting and had significantly more “positive affectivity” in the current trait. Although no significant associations were found, there was a trend for late presenters to have higher education levels, less spiritual longing, less accurate explanation of their illness, less anxiety in the trait scale, and more conscientiousness than the controls. Conclusion: As patients with late presentation for BC differ in specific psychological and sociodemographic characteristics from patients with early BC, the findings of this pilot project warrant additional investigations to identify further specific characteristics and motivations. Identifying patients at risk for late presentation and encouraging them to accept an earlier diagnosis could help to improve their therapy and, finally, their outcome.

Purpose Ligand-dependent corepressor (LCoR) and receptor-interacting protein 140 (RIP140/NRIP1) play an important role in the regulation of multiple oncogenic signaling pathways and the development of cancer. LCoR and RIP140 form a nuclear complex in breast cancer cells and are of prognostic value in further prostate and cervical cancer. The purpose of this study was to analyze the regulation of these proteins in the development of cervical intraepithelial neoplasia (CIN I–III). Methods Immunohistochemical analysis was obtained to quantify RIP140 and LCoR expression in formalin-fixed paraffin embedded tissue sections of cervical intraepithelial neoplasia samples. Tissue (n = 94) was collected from patients treated in the Department of Gynecology and Obstetrics, Ludwig-Maximilians-University of Munich, Germany, between 2002 and 2014. Correlations of expression levels with clinical outcome were carried out to assess for prognostic relevance in patients with CIN2 progression. Kruskal–Wallis test and Mann–Whitney U test were used for data analysis. Results Nuclear LCoR overexpression correlates significantly with CIN II progression. Nuclear RIP140 expression significantly increases and nuclear LCoR expression decreases with higher grading of cervical intraepithelial neoplasia. Cytoplasmic RIP140 expression is significantly higher in CIN III than in CIN I or CIN II. Conclusion A decrease of nuclear LCoR expression in line with an increase of dedifferentiation of CIN can be observed. Nuclear LCoR overexpression correlates with CIN II progression indicating a prognostic value of LCoR in cervical intraepithelial neoplasia. Nuclear and cytoplasmic RIP140 expression increases significantly with higher grading of cervical intraepithelial neoplasia underlining its potential role in the development of pre-cancerous lesions. These findings support the relevance of LCoR and RIP140 in the tumorigenesis indicating a possible role of LCoR and RIP140 as targets for novel therapeutic approaches in cervical intraepithelial neoplasia and cervical cancer.

Purpose Galectins are carbohydrate-binding proteins with multiple effects on cell biology. Research shows that they play an important role in tumor development and progression. Therefore, in this study, the presence of Galectin-8 and -9 (Gal), both already known as prognostic factors in other tumor entities, were investigated in cervical cancer. Our aim was to examine the association of Gal-8 and -9 expression with histopathological markers and survival of the patients. Methods Gal-8 and -9 expression was investigated in 250 cervical cancer samples by immunohistochemistry. The staining was evaluated using the immunoreactive score (IRS). The results were correlated to clinical and pathological data. The correlation of Gal-8 and -9 expression with overall and relapse-free survival was analyzed. Results Expression of Gal-8 was associated with negative N-status and lower FIGO status. Detection of Gal-9 was connected to negative N-status and lower grading regarding all specimens. A correlation of Gal-9 with lower FIGO status was detected for squamous cell carcinoma (SCC) only. Expression of Gal-8 was associated with relapse-free survival of SCC patients in a positive manner. Gal-9 expression was associated with better overall survival. Conclusion Our results suggest that expression of both galectins is inversely associated with tumor stage and progression. Gal-8 expression is associated with relapse-free survival of patients with SCC, while presence of Gal-9 in cervical cancer is associated with a better prognosis in regard of overall survival.

The aim of this study was to analyze the expression of peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor α (RxRα), a binding heterodimer playing a pivotal role in the successful trophoblast invasion, in the placental tissue of preeclamptic patients. Furthermore, we aimed to characterize a possible interaction between PPARγ and H3K4me3 (trimethylated lysine 4 of the histone H3), respectively H3K9ac (acetylated lysine 9 of the histone H3), to illuminate the role of histone modifications in a defective trophoblast invasion in preeclampsia (PE). Therefore, the expression of PPARγ and RxRα was analyzed in 26 PE and 25 control placentas by immunohistochemical peroxidase staining, as well as the co-expression with H3K4me3 and H3K9ac by double immunofluorescence staining. Further, the effect of a specific PPARγ-agonist (Ciglitazone) and PPARγ-antagonist (T0070907) on the histone modifications H3K9ac and H3K4me3 was analyzed in vitro. In PE placentas, we found a reduced expression of PPARγ and RxRα and a reduced co-expression with H3K4me3 and H3K9ac in the extravillous trophoblast (EVT). Furthermore, with the PPARγ-antagonist treated human villous trophoblast (HVT) cells and primary isolated EVT cells showed higher levels of the histone modification proteins whereas treatment with the PPARγ-agonist reduced respective histone modifications. Our results show that the stimulation of PPARγ-activity leads to a reduction of H3K4me3 and H3K9ac in trophoblast cells, but paradoxically decreases the nuclear PPARγ expression. As the importance of PPARγ, being involved in a successful trophoblast invasion has already been investigated, our results reveal a pathophysiologic connection between PPARγ and the epigenetic modulation via H3K4me3 and H3K9ac in PE.

Purpose: Differential efficacy of newly registered therapies in subgroups of metastatic breast cancer (MBC) is an important consideration for subsequent use in clinical practice. Unfortunately, such subgroup analyses often are exploratory and rarely statistically adequately powered and may thus be misleading. This analysis aimed to explore a potentially different treatment response to i.v. therapies between visceral and non-visceral MBC. Methods: In a systematic literature analysis (PubMed) comprising phase III registration studies for MBC from 1994 to 2014, differences in outcome were evaluated regarding progression-free survival, time to progression, overall survival (OS), and visceral versus non-visceral disease. The impact of HER2 and hormone receptor status was also considered. A total of 16 studies comprising 13,083 patients were selected by considering the information given in the medical product’s professional information and the decision of the US Food and Drug Administration or the European Medicine Agency for approval of the respective therapeutic agents now used in the treatment of MBC. Results: No statistically significant differences regarding treatment response and therapy benefit were found in MBC patients with visceral versus non-visceral metastases based on reported hazard ratios and confidence intervals in registration trials. Interesting but nonsignificant differences were found regarding a distinct therapy benefit regarding different metastasis locations in 4 studies. Conclusion: For targeted i.v. therapies based on biomarker selection, there is a trend – although not significant – toward a benefit (OS) from combination therapies favoring visceral disease. However, at the present time, metastasis localization should not be used as a predictive marker for choice of systemic therapy in MBC.

Purpose: COX-2 overexpression and elevated levels of prostaglandin E2 (PGE2) play an important role in breast cancer carcinogenesis. Recently, expression of the PGE2 receptor EP3 has been shown to be a positive prognostic factor in breast cancer. This study analyzes the functional aspects of targeting EP3 in breast cancer cell lines. Material and methods: EP3 and EP1 expressions were determined in five breast cancer cell lines on the mRNA- and the protein-level. The selected cell lines were subsequently stimulated for 24-72 hrs with 10-1,000 nM of PGE2, the EP1/EP3 agonist sulprostone and the EP3 antagonist L798,106. Cell proliferation was determined via BrdU-assay, migration via scratch assay, EP3, Gi-protein and p-ERK1/2 expressions via Western blot and cAMP concentrations via ELISA. The Mann-Whitney-U-test was used to test for statistical significance. Results: The cell lines T-47D (EP3 expression 77.7%) and SK-BR-3 (EP3 expression 48.7%) were chosen. EP3 antagonism reduced its expression on SK-BR-3 significantly, while no effect was observed on T-47D. The proliferation and migration of SK-BR-3 cells were significantly reduced due to treatment with the EP1/3 agonist, the EP3 antagonist or a combination of both. Neither agonism nor antagonism influenced cell proliferation or migration in T-47D. In SK-BR-3, EP3 antagonism showed a significant decrease in Gi-protein levels, an increase in cAMP levels, and no significant change in p-ERK1/2 expression. Conclusion: Antagonism of the EP3 receptor results in a reduced proliferation and migration of SK-BR-3 breast cancer cells, potentially mediated via a Gi-protein-cAMP pathway. The results suggest that EP3 plays a role in tumorigenesis. This is in accordance with the cell culture data of other gynecological tumors, but it is conflicting in so far, as positive EP3 expression is clinically a positive prognostic marker in breast cancer. Therefore, other factors may be important in explaining this contradiction.

Breast cancer (BC) is the most frequent cancer in women and the leading cause of cancer death in females worldwide. Rapid research advancements add to the complexity of treatment options for this disease. It is known that the quality of patients’ care is deeply affected by healthcare professionals following these advancements. There is a growing need for academic education to increase clinical knowledge and skills of physicians treating BC patients. The certificate of Competence in Breast Cancer Program (CCB) is a Certificate in Advanced Studies (CAS) organized by the European School of Oncology in cooperation with Ulm University (Germany), which focuses on both the clinical and scientific competence required for improving quality in the management of BC patients. This paper describes the experience of the second CCB cohort (CCB2), which brought together 24 physicians from four continents who shared the common will to improve their competence and skills in BC treatment.

Background Maternal immunological rejection of the semi-allogenic fetus is discussed as one of the significant factors involved in early pregnancy loss. An array of cytokines secreted by both maternal and fetal cells is involved in generating a delicate maternal immune tolerance. Interleukin 7 (IL-7) is discussed to play a key role in pro-inflammatory processes, but there is still limited insight into the pathophysiological input on placentation and embryonic development in early pregnancy loss. Patients and methods Cytokine level differences were identified with quantitative real-time PCR in placental tissue from spontaneous abortions (SA) (n=18), recurrent spontaneous abortions (RSA) (n=15), and healthy pregnancies (n = 15) at gestational weeks 7 to 14. Protein expression of IL-7 in the decidua was investigated by immunohistochemistry. IL-7 expressing cells were identified with double-immunofluorescence. Results Decidua of women with RSA expressed almost 51-times higher values of IL-7 in gene expression analysis. Immunohistochemistry identified a significant upregulation of IL-7 in the decidua of RSA specimens (p = 0.013) and in the decidua of women with SA (p = 0.004). Double-immunofluorescence confirmed decidual stroma cells as IL-7 expressing cells. Conclusion Significantly elevated IL-7 values in the decidua of spontaneous and recurrent miscarriages imply a crucial role of the cytokine in the signaling at the feto-maternal interface of the placenta. An overexpression of IL-7 could result in early pregnancy loss by inducing a pro-inflammatory environment. Proven to be valuable in other autoimmune diseases, targeting IL-7 signaling therapeutically may prove to be a very beneficial treatment option for RSA patients.

ObjectiveOvarian cancer is the most lethal gynecologic cancer. Resveratrol (RSV) is known to alter metabolism in cancer. It affects the nuclear retinoid-X-receptor (RXR), which implies a modulating effect of RXR to gynaecologic cancers. Furthermore, RSV targets Sirtuin1 (Sirt1), a histone deacetylase.Study design123 tissue samples of patients with serous or mucinous ovarian cancer were examined for expression of Sirt1 and RXR. Ovarian cell lines were treated with RSV and consequences on viability and apoptosis were evaluated. The influence of RSV to Sirt1 and RXR expression was analyzed by western blottingResultsA correlation of nuclear Sirt1 and RXRα expression could be detected (p = 0.006). Co-expression of nuclear RXRα and cytoplasmic (p = 0.026) or nuclear (p = 0.041) Sirt1 was associated with significantly increased overall survival in advanced tumour stages. Viability was decreased in all cell lines after stimulation with resveratrol, while cell apoptosis was increased. RSV treatment led to significant lower Sirt1 expression in A2780 cells (p = 0.025) and significant increased RXR expression in cisA2780 cells (p = 0.012)ConclusionIn order to use RSV as medical target, studies could be developed to improve the understanding of drug resistance mechanisms and consequently improve treatment outcome.

Purpose The tumour’s ability to metastasize is the major cause for fatal outcomes in cancer diseases. In breast cancer, aberrant E-Cadherin expression has been linked to invasiveness and poor prognosis. Method We assessed expression of E-Cadherin by immunohistochemistry in primary tumour tissue from 125 female breast cancer patients. Staining intensities were analysed using the immunoreactive score (IRS). We investigated E-Cadherin expression and its associations with clinicopathological parameters (age, tumour size, lymph node status, grade, hormone receptors, Her2 Status) as well as with recurrence and survival. Results Increased, rather than aberrant E-Cadherin expression was found and was associated with poor outcome (p = 0.046). Our data show an association between elevated E-Cadherin in primary tumour tissue and an unfavourable negative prognosis in patients. Conclusion This association was somehow unexpected as loss of E-Cadherin has long been regarded as a prerequisite for development of invasiveness and metastases. Our findings support the notion that E-Cadherin promotes, rather than suppresses, development of metastasis and invasiveness.

Gestational diabetes mellitus (GDM) is known to increase the risk for feto-maternal complications during pregnancy. A state of low-grade inflammation, with elevated levels of proinflammatory molecules, similar to patients with obesity or diabetes mellitus type 2 has also been partly described in GDM. The placenta, as unique interface between mother and fetus, is not only passively affected by changes in one of these organisms, but also acts as a modulator by expressing hormones and cytokines. This study aimed to investigate the expression of the proinflammatory cytokines Interleukin (IL) 7, 8 and 15 in GDM in placental tissue. A total number of 80 placentas were included (40 GDM/40 control group). The expression of IL-7, 8 and 15 was investigated in extravillous trophoblast (EVT) and syncytiotrophoblast (SCT) by immunohistochemistry and immunofluorescence double staining. The immunohistochemical staining was evaluated with the semiquanitfied immunoreactive score (IRS). While the expression IL-15 was significantly upregulated in EVTs of women with GDM. The expression of IL-8 was significantly decreased in EVT of the GDM group. Furthermore, significant fetal sex specific differences were detectable in all three cytokines. Our findings suggest an involvement of the investigated cytokines in the maintenance of a state of chronic low-grade inflammation on placental level in patients suffering from GDM.

Several risk factors like obesity and hyperlipidemia were described for endometrial cancer. Here, the nuclear NAD-dependent histone-deacetylase Sirtuin1 (SIRT1) seems to be important. SIRT1 is also involved in cell regulatory mechanisms and can serve as tumor promotor or suppressor. Its role in tumor biology is not clear yet. In this study, we evaluated and correlated the SIRT1 expression with patients’ tumor characteristics in endometrioid and clear-cell cancer of the uterus. 65 paraffin-embedded samples of patients with endometrial and clear-cell cancer of the uterus were immunohistochemically stained and SIRT1 expression was evaluated by immunoreactive score. The results were correlated to clinical and pathological tumor characteristics as well as to the expression of ARID1A and β-Catenin. The staining was significantly more intensive in uterine endometrioid carcinoma compared to uterine clear-cell carcinoma (p = 0.007). The expression of SIRT1 correlated significantly with the membranous expression of β-Catenin (p = 0.028) and ARID1A (p = 0.021). Patients with positive Sirtuin1 expression had a significantly better progression-free survival (p = 0.042), the overall survival showed a trend towards a better prognosis (p = 0.070). SIRT1 expression seems to be associated with improved progression-free survival in uterine cancer (endometrioid and clear-cell) and is correlated to the tumor suppressors β-Catenin and ARID1A. Further studies are necessary to elucidate the role of SIRT1 in uterine and ovarian cancer and its potential as a therapeutic target.

Purpose Breast cancer is the leading cause of cancer death in females. Histone modifications have been shown to have an influence on the gene expression. This study focusses on the histone modifications H3K9ac and H3K4me3 in breast cancer and their impact on survival Methods H3K4me3 and H3K9ac expression was immunohistochemically examined in 235 tissue samples. Results Positive estrogen receptor status was correlated with a higher IRS of the nuclear (p = 0.033), and of the cytoplasmic H3K4me3 staining (p = 0.009). H3K9ac intensity was associated to the Her2 status (p = 0.045) and to poor prognosis in cells with positive Ki67 status (p = 0.013). A high intensity of nuclear H3K4me3 staining was found to be correlated with a lower 10-year-survival (p = 0.026) and with lower breast cancer-specific survival (p = 0.004). High percentage score (> 190) of H3K9ac expression was correlated to worse breast cancer-specific survival (p = 0.005). Shorter progression-free survival was found in patients with nuclear (p = 0.013) and cytoplasmic H3K4me3expression (p = 0.024) and H3K9ac expression (p = 0.023). Conclusion This analysis provides new evidence of histone modifications in breast cancer. High H3K4me3 and H3K9ac expression was correlated with survival rates. Further investigation of histone modifications in breast cancer could lead to a more profound understanding of the molecular mechanisms of cancer development and could result in new therapeutic strategies.

To evaluate delayed interval deliveries in multiple gestations in regard of delayed interval and neonatal survival and to provide a protocol. Data of multiple pregnancies with delayed interval delivery at a tertiary maternity unit between 2002 and 2017 were collected. Contraindications for evaluation of a delay of the delivery of the remaining child were: severe maternal blood loss, poor maternal general condition, preeclampsia, placental abruption, fetal distress, serious congenital malformations of the remaining child, chorioamnionitis, and premature rupture of membranes of the second fetus. A total of 14 cases was included in this retrospective monocentric analysis. The cohort comprised nine twin and five triplet pregnancies. Mean gestational age at delivery of the first fetus was 21 + 6 and 26 + 0 of the retained fetus, respectively. The earliest delivery of the first fetus was at 15 + 2 weeks. The mean interval of the delay was 29.3 days (2–82 days). Mortality of the first fetuses was 53.3%, while it was 17.6% for the retained fetuses. Maternal outcome was good in general: two cases of major blood loss occurred with the necessity of a blood transfusion. Delayed interval delivery is a reasonable approach in cases of an imminent preterm birth in multiple gestations which can be performed with a good fetal outcome and limited maternal risks. The situation when this procedure may be an option always comes unexpected. Therefore, the team of perinatologists should keep it in mind as one potential therapeutic approach. In addition, a standard protocol for the procedure should be established in the perinatal center.

The aim of this study was to evaluate the effect of a pilot interdisciplinary inhouse training in palliative care (PC) for gynecological oncologists. Competencies of participants from a gynecological university department were evaluated taking part in an interdisciplinary PC course in a pre and post design. The multiprofessional course covered basic principles of PC, symptom management and communication taught by PC specialists. Competencies were evaluated using self-designed questionnaires before (ISPG-1), right after (ISPG-2), and 6 months after the training (ISPG-3) (inhouse seminar palliative care in gynecology: ISPG). 31 persons from the department of gynecology took part in the course, of which 27 answered the first questionnaire (seven nurses (26%), 19 doctors (71%), one profession not indicated (3%), median working experience in gynecological oncology: 5 years). Return rates were: ISPG-1 27/31 (87.1%), ISPG-2 20/31 (64.5%) and IPSG-3 14/31 (45.2%). A more positive attitude towards PC could be observed in the majority of participants after the course (ISPG-2 62%, ISPG-3 71%). They felt more competent in the care of palliative patients (46%). PC would be initiated earlier and the interaction with other disciplines was improved (ISPG-2 85%, ISPG-3 100%). The participants assessed a significant improvement of their skills in all palliative fields which were analyzed. PC inhouse training improves the understanding of PC and the interdisciplinary approach in the management of patients with advanced disease. It is a feasible and useful instrument to improve the competencies in generalist PC of specialists in gynecological oncology.

The Fas-antigen is a cell surface receptor that transduces apoptotic signals into cells. The purpose of this study was to evaluate FasL expression in breast cancer and to elucidate the role of its signaling in different breast cancer cell lines. T47D and MCF7 cells were used and cultured in Dulbecco’s modified Eagle’s medium. FasL translocation to the membrane was achieved by culturing the cells in the presence of human interferon-γ (IFNγ). Translocation was detected by immunofluorescence. The ability of a Fas:Fc fusion protein to trigger apoptosis in these cells was investigated by cell death detection ELISA. After incubation with IFNγ for 4 h and 18 h, apoptosis was assessed in response to treatment with Fas:Fc. Immunofluorescence revealed that the used cell lines were positive for FasL which was increased and changed to more membrane-bound FasL expression after IFNγ stimulation. After stimulation with 50 IU/ml IFNγ, Fas:Fc significantly increased MCF7 apoptosis (1.39 ± 0.06-fold, p = 0.0004) after 18 h. After stimulation with 100 IU/ml, Fas:Fc significantly increased apoptosis both after 4 h (1.49 ± 0.15-fold, p = 0.018) and 18 h (1.30 ± 0.06-fold, p = 0.013). In T47D cells this effect was seen after 4 h of stimulation with 50 IU/ml and addition of Fas:Fc (1.6 ± 0.08-fold, p = 0.03). Membrane-bound FasL expression could be induced by IFNγ in a breast cancer cell model. More importantly, in the presence of IFNγ the Fas:Fc fusion protein was able to transmit pro-apoptotic signals to T47D and MCF7 cells, significantly inducing apoptosis. The current findings support further in vivo studies regarding FasL activation as a potential target for therapeutic intervention in breast cancer.

Purpose of the investigation: Vulvovaginal candidosis (VVC) is a common vaginal infection affecting almost 75% of all women once per lifetime. Vaginal associated immunity is important in the protection against VVC. The purpose of this study was to evaluate a potential role of IL-23, IFN-alpha, and IFN-beta in the local immune response against VVC. Materials and Methods: The study included 202 non-pregnant women;71 patients with clinical symptoms of VVC and 131 asymptomatic patients served as control. IL-23, IFN-alpha, and IFN-beta were measured in the vaginal fluid by ELISA. Microbiological cultures were used for Candida detection. Results: C. albicans was detected in 67.6% of patients, C. glabrata in 21.1% of patients, and 5.6% were infected with C. krusei or coinfected with C. albicans and C. krusei. Levels of IL-23 (p < 0.001) and IFN-beta (p < 0.017) were significantly lower in the VVC group. IFN-alpha was elevated in the VVC group compared to the asymptomatic patients (p < 0.001). Conclusion: IL-23 and IFN-beta seem to play a protective role against VVC. Decreased levels in VVC patients suggest a compromised local immune response at the time of occurrence of symptoms. In contrast, IFN-alpha seems to be released once the infection has occurred. These cytokines may be prospective targets in the treatment and prevention of primary and recurrent vaginal infections with Candida species.

Prostaglandin induced signalling is involved in different cancers. As previously described, the EP3 receptor expression decreases with increasing stage of cervical intraepithelial lesions (CIN). In addition, in cervical cancer EP3 is an independent prognosticator for overall survival and correlates with FIGO stages. Currently the role of Prostaglandin 2 receptor 2 (EP2) in CIN is unknown. The aim of this study was to analyse the expression of EP2 for potential prognostic value for patients with cervical dysplasia. EP2 expression was analysed by immunohistochemistry in 33 patient samples (CIN1–3) using the immune-reactivity scoring system (IRS). Expression levels were correlated with clinical outcome to analyse prognostic relevance in patients with CIN2. Data analysis was performed using non parametric Kruskal–Wallis and Spearman rank sum test. Cytoplasmic expression levels of EP2 correlated significantly (p n = 8), 3 in CIN2 (n = 9) and 6 in CIN3 (n = 16). Comparing regressive (n = 3, median IRS = 2) to progressive (n = 6, median IRS = 4) CIN2 cases the median IRS differed significantly (p = 0.017). Staining intensity (p = 0.009) and IRS (p = 0.005) of EP2 and EP3 correlate inversely. EP2 expression level significantly increases with higher grade of CIN and could qualify as a potential prognostic marker for the regressive or progressive course in CIN2 lesions. These findings emphasize the significant role of PGE2 signalling in CIN and could help to identify targets for future therapies.

Aim: Cervical intraepithelial neoplasia (CIN) is commonly divided into three grades. Guidelines increasingly recommend surgery only in CIN 3 lesions. We investigated markers to evaluate differences in CIN 2 and 3 lesions as well as possible predictors for regression/progression in CIN 2 lesions. Materials & methods: Biopsies (n = 128) of healthy cervical tissue and CIN 1–3 were stained for Sialyl Lewis a, Sialyl Lewis x, Lewis y, Gal-3, Gal-7, STMN1 and p16. Results: We observed significant differences between CIN 2 and 3 lesions for Sialyl Lewis a, Sialyl Lewis x, Gal-3, Gal-7, STMN1 and p16. Expression of Sialyl Lewis a was significantly higher in CIN 2 patients who progressed during follow-up. Conclusion: Significant differences in marker expression support the differentiation of CIN 2 and 3. Lewis a may help to predict progression/regression in CIN 2 patients.