The role of E-Cadherin expression in primary site of breast cancer.

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.

Serial Monitoring and Hyperimmunoglobulin versus Standard of Care to Prevent Congenital Cytomegalovirus Infection: A Phase III Randomized Trial.

INTRODUCTION: Nonrandomized studies support the potential of cytomegalovirus hyperimmunoglobulin (CMV-HyperIg) in preventing maternofetal CMV transmission, but prospective interventional studies show equivocal results. We pre-sent a prospective phase-III international randomized open-label trial on the potential effect of CMV-HyperIg following serial monitoring of CMV serostatus. METHODS: CMV-seronegative pregnant women (gestational age [GA] <14 weeks) were 1:1 randomized to monthly CMV-serostatus monitoring and CMV-HyperIg upon seroconversion (treatment), or routine prenatal care with CMV-serostatus testing at end of pregnancy (control). Ethical considerations required that control subjects with confirmed seroconversion be offered Cytotect®. The primary endpoint was the proportion of fetuses/newborns with congenital CMV infection. Secondary endpoints included neonatal CMV disease and safety during the 24-month follow-up. RESULTS: The treatment arm counted 4,800 randomized subjects: 52 seroconverted (median GA 24 [11-35] weeks), of which 45 completed follow-up. The control arm counted 4,735 randomized subjects: 42 seroconverted, of which 34 completed follow-up (evaluable data for 28 newborns) and 8 subjects chose off-label Cytotect®. Congenital CMV rates were 13/28 newborns (46.4% [CI 27.51; 66.13]) vs. 16/45 newborns (35.6% [CI 21.87; 51.22]) in control and treated arms, respectively (p = 0.46). Newborn CMV disease was mostly mild and spontaneously resolving. There were no major safety concerns. The target sample was not reached within an acceptable time frame. CONCLUSIONS: Serial monitoring of CMV serostatus with CMV-HyperIg treatment was associated with a mild nonsignificant reduction in the vertical CMV transmission rate. Studies on the optimal preventive strategy are hampered by epidemiological and ethical challenges and should focus on GA-dependent transmission rates and accurate dating of infection.

Prevention of Cervical Cancer: Guideline of the DGGG and the DKG (S3 Level, AWMF Register Number 015/027OL, December 2017) - Part 1 with Introduction, Screening and the Pathology of Cervical Dysplasia.

Aims Annual opportunistic screening for cervical carcinoma has been carried out in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as the guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany. Methods With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline. Recommendations The first part of this short summary presents the pathological basis and considers various questions related to screening for cervical cancer. As also reported in earlier reviews, the meta-analysis by Kleijnen Systematic Reviews showed that HPV-based screening offers better protection against invasive cervical cancer compared to cytology-based screening. The authors of this guideline therefore recommend - in accordance with the guideline of the Joint National Committee of Germany (Gemeinsamer Bundesauschuss, G-BA) - that women aged 35 and above should be examined at regular intervals (at least every 3 years) and undergo HPV-based screening. Co-testing can also be carried out. Women between the ages of 20 and 35 should have cytological screening every 2 years.

Prevention of Cervical Cancer: Guideline of the DGGG and the DKG (S3 Level, AWMF Register Number 015/027OL, December 2017) - Part 2 on Triage, Treatment and Follow-up.

Aims Annual opportunistic screening for cervical carcinoma has been done in Germany since 1971. The creation of this S3 guideline meets an important need, outlined in the National Cancer Plan, with regard to screening for cervical cancer, as this guideline aims to provide important information and support for planned organized screening for cervical cancer in Germany. Methods With the financial support of German Cancer Aid, 21 professional societies developed evidence-based statements and recommendations (classified using the GRADE system) for the screening, management and treatment of precancerous conditions of the cervix. Two independent scientific institutes compiled systematic reviews for this guideline. Recommendations The second part of this short summary deals with the triage, treatment and follow-up care of cervical dysplasia. With regard to those women who do not participate in screening, the guideline authors recommend sending out repeat invitation letters or an HPV self-collection kit. Colposcopy should be carried out for further investigation if cytology findings are Pap II-p and HPV test results are positive or if the results of an HPV 16 or HPV 18 screening test are positive. A single abnormal Pap smear should be triaged and investigated using HPV testing or p16/Ki67 dual staining.

Delayed interval delivery in multiple gestations: the Munich experience.

OBJECTIVE: To evaluate delayed interval deliveries in multiple gestations in regard of delayed interval and neonatal survival and to provide a protocol. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

TA-MUC1 as detected by the fully humanized, therapeutic antibody Gatipotzumab predicts poor prognosis in cervical cancer.

BACKGROUND: Gatipotuzumab is a fully humanized antibody which was designed to detect a cancer-specific glyco-modification of MUC1 (termed 'TA-MUC1') and which was optimized to effectively trigger antibody-dependent-cell-mediated cytotoxicity (ADCC) in cancer cells. Clinical trials investigating therapeutic efficacy of this antibody have been published recently. The current analysis aimed to determine whether TA-MUC1-as detected by Gatipotuzumab-is expressed in cervical cancer tissue and whether binding of Gatipotuzumab is associated with clinico-pathological variables including recurrence free (RFS) and overall survival (OS). METHODS: Cervical cancer tissue (n = 250) was stained for TA-MUC1 using Gatipotuzumab employing a standardized immunohistochemistry protocol. Staining was scored by applying the IR-score. Results were binarized and tested for association to clinico-pathological parameters. RESULTS: TA-MUC1 as stained by Gatipotuzumab was detected in 188 (75.2%) out of the 250 cervical cancer cases investigated. Expression of TA-MUC1 was restricted to cancer cells and was positively correlated with viral oncoprotein E6. Membrane staining of TA-MUC1 predicted significantly reduced RFS and OS. Importantly, expression of TA-MUC1 at the cell surface identified a group of early stage cervical cancer patients with exceptional short RFS and OS. CONCLUSIONS: We report TA-MUC1-the antigen detected by Gatipotzumab-to be widely expressed in cervical cancer tissue and to localize to the cell membrane. The latter is seen as a pre-requisite to target this epitope by antibody-drug conjugates or antibodies eliciting ADCC. Since especially, membrane localization of TA-MUC1 predicted poor prognosis, evaluating Gatipotuzumab for its therapeutic efficacy in cervical cancer may turn attractive.

The G protein-coupled estrogen receptor (GPER/GPR30) may serve as a prognostic marker in early-stage cervical cancer.

BACKGROUND: Estrogen signalling is transmitted via various receptors and multiple intracellular signalling pathways. Estrogen receptor alpha (ERα)-mediated transcription of target genes has been demonstrated to be closely linked to human papilloma virus (HPV)-induced carcinogenesis in case of cervical cancer. So far, the role of non-genomic estrogen signals in cervical cancer, e.g. transmitted by the G protein-coupled estrogen receptor (GPER) remains to be rather elusive. Today's knowledge on the role of GPER in cervical cancer is sparse and-to the best of our knowledge-GPER has not been investigated in context with clinicopathological parameters or prognosis of cervical cancer. Therefore, the current study investigated whether GPER is expressed in cervical cancer tissue. Further, GPER was correlated to clinicopathological parameters, tissue markers of cervical carcinogenesis and to patient overall and recurrence-free survival. MATERIALS AND METHODS: Cervical cancer tissue was collected from 156 patients during surgery between 1993 and 2002. GPER immunostaining was performed on all the cases and correlated to clinicopathological data. More than half of all patients were diagnosed at advanced stage (FIGO II-IV 93/156; 59.6%) of disease. The large majority of patients presented with tumours of intermediate or high grade (G2-3 140/152, 92.1%). 22 cervical cancer-related deaths (22/156, 14.1%) were documented during the follow-up period. RESULTS: GPER was detected in various subcellular staining patterns. In 129/156 (82.7%) cases GPER was expressed in the tumour cell cytoplasm (GPERcyt). GPER immunopositivity at the cell membrane (GPERmem) was found in 114/156 (73.1%) cases. While co-occurrence of both membrane and cytoplasmic staining (GPERcyt + GPERmem) was detected in the majority of tissue samples (101/156; 64.7%), only few cases (14/156, 9.0%) were classified as not expressing GPER at all. GPERcyt was positively correlated with tumour grade. Statistical associations of GPER and both p16 and p53 were detected. Finally, immunopositivity of GPERcyt was predictive for favourable overall as well as recurrence-free survival in cervical cancer of early stage (FIGO I). CONCLUSION: This retrospective study reports GPERcyt to be associated with improved overall and recurrence-free survival in early-stage cervical cancer. Further investigations are needed thus to determine whether this observation may be of clinical impact. Interestingly, Raloxifene-a GPER-activating selective estrogen receptor modulator-has recently been demonstrated to be preventive for cervical cancer relapse in mice. Whether this effect is only reliant on raloxifene blocking ERα or may also be related to activation of GPER remains to be determined.

Primary Human Cytomegalovirus (HCMV) Infection in Pregnancy.

BACKGROUND: In 0.5-4% of pregnancies, the prospective mother sustains a primary infection with human cytomegalovirus (HCMV). An HCMV infection of the fetus in the first or second trimester can cause complex post-encephalitic impairment of the infant brain, leading to motor and mental retardation, cerebral palsy, epilepsy, retinal defects, and progressive hearing loss. METHODS: This review is based on pertinent publications from January 2000 to October 2016 that were retrieved by a selective search in PubMed employing the terms "cytomegalovirus and pregnancy" and "congenital cytomegalovirus." RESULTS: 85-90% of all neonates with HCMV infection are asymptomatic at birth. The main long-term sequela is hearing impairment, which develops in 8-15% of these affected children. Hygienic measures can lower the risk of primary HCMV infection in pregnancy by 50-85%. The first randomized and controlled trial (RCT) of passive immunization with an HCMV-specific hyper - immune globulin (HIG) preparation revealed a trend toward a lower risk of congenital transmission of the virus (30% versus 44% with placebo, p = 0.13). The effect of HIG was more marked in the initial non-randomized trial (15% versus 40%, p = 0.02). The RCT also showed HIG to be associated with a higher frequency of fetal growth retardation and premature birth (13% versus 2%, p = 0.06). Valaciclovir is a further, non-approved treatment option. CONCLUSION: In the absence of an active vaccine against HCMV, counseling about hygienic measures may currently be the single most effective way to prevent congenital HCMV infection. Moreover, HCMV serologic testing is recommended in the guideline of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF). Further randomized trials of treatment with HIG and with valaciclovir are urgently needed so that the options for the prevention and treatment of congenital HCMV infection can be assessed.

Influence of Circulating Tumour Cells on Production of IL-1α, IL-1ß and IL-12 in Sera of Patients with Primary Diagnosis of Breast Cancer Before Treatment.

BACKGROUND: Circulating tumour cells (CTCs) have been found to be a prognostic marker for reduced disease-free survival (DFS), distant DFS, breast cancer-specific survival, and overall survival (OS) before the start of systemic treatment. Determination of CTCs with the CellSearch System (Veridex, Raritan, NJ, USA) is a valuable but time-consuming and costly method. Therefore, the aim of this study was to evaluate cytokine profiles as a marker for CTC involvement. PATIENTS AND METHODS: Patients chosen for this study were defined as women with breast cancer who agreed to participate in the phase I SUCCESS study. CTC analysis, the blood sampling time points, and the methodology were prospectively designed, and the prognostic value of the CTCs was defined as a scientific objective of the study protocol. A total of 100 patients positive for CTCs and an additional 100 patients negative for CTCs were matched into pairs. Matching criteria were histopathological grading, lymph node status, hormone receptor type, TNM classification and survival vs. tumour associated death. Commercial enzyme-linked immunosorbent assay (ELISA) was used to screen the blood serum samples for the Th1 cytokines: interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 12 (IL-12), IL-1α, IL-1ß, IL-2 and IL-18. The correlation of cytokine levels to the matching criteria listed above were analyzed with the Spearman correlation coefficient and the Mann-Whitney-U rank-sum test. RESULTS: The IL-1α level was significantly lower in the CTC-positive patient group (p=0.043) but significantly higher in the CTC-negative progesterone receptor-positive collective (p=0.029). Furthermore, in patients who survived, significantly higher IL-12p40 levels were found in those with lymph node involvement (p=0.041) and those with triple-negative breast cancer (p=0.043). Of patients who died, those with oestrogen receptor-negative disease had higher IL-1α (p=0.050) and higher IL-1ß (p=0.034) levels. Moreover, of those who died, those with triple-negative breast cancer had significantly higher IL-1α levels (p=0.033). In patients with grade 2 tumour, patients with HER2/neu expression had significantly higher IFN-γ levels (p=0.031) and those with no lymph node involvement had significantly higher IL-1α levels (p=0.014). In the collective with grade 3 tumour, patients with progesterone receptor-negative disease had significantly higher IL12p70 concentrations (p=0.048), while those with triple-negative breast cancer had lower IL12p40 levels (p=0.033). CONCLUSION: Regarding CTC involvement, we speculate that IL-1α might be a marker for the release of tumour cells into the circulation and not into the lymphatic system. In addition, IL-1α like IL-1ß appears to be related to CTC release in patients with breast cancer.

Real-Time qPCR-Based Detection of Circulating Tumor Cells from Blood Samples of Adjuvant Breast Cancer Patients: A Preliminary Study.

BACKGROUND: Circulating tumor cells (CTCs) are cells that detach from a primary tumor, circulate through the blood stream and lymphatic vessels, and are considered to be the main reason for remote metastasis. Due to their origin, tumor cells have different gene expression levels than the surrounding blood cells. Therefore, they might be detectable in blood samples from breast cancer patients by real-time quantitative polymerase chain reaction (RT-qPCR). MATERIALS AND METHODS: Blood samples of healthy donors and adjuvant breast cancer patients were withdrawn and the cell fraction containing white blood cells and tumor cells was enriched by density gradient centrifugation. RNA was isolated and reverse transcribed to cDNA, which was then used in TaqMan real-time PCR against cytokeratin (CK)8, CK18 and CK19. 18S and GAPDH were used as controls. RESULTS: All 3 CKs were, on average, found to be significantly higher expressed in adjuvant breast cancer samples compared to negative controls, probably due to the presence of CTCs. Unfortunately, gene expression levels could not be correlated to tumor characteristics. CONCLUSIONS: RT-qPCR could make up a new approach for the detection of CTCs from blood samples of breast cancer patients, but a correlation of the PCR data to gold standard methods in CTC detection would help to further improve the informative value of the qPCR results.

Determination of Interleukin-4, -5, -6, -8 and -13 in Serum of Patients with Breast Cancer Before Treatment and its Correlation to Circulating Tumor Cells.

BACKGROUND/AIM: Circulating tumor cells (CTCs) in women with breast cancer are an indication of prognosis before starting systemic treatment. The aim of this study was the evaluation of cytokine profiles as marker for CTC involvement. MATERIALS AND METHODS: The analysis of CTCs, the time of blood sampling and the methodology were prospectively designed. There were two groups of patients: 100 women with a positive result for presence of CTCs and 100 women negative for CTCs. These groups were matched into pairs by tumor factors and survival/death. A multi-array ELISA was used to screen T-helper cell (Th) 2 cytokines. The results were analyzed by Spearman correlation coefficient and Mann-Whitney U-test. RESULTS: In patients who were CTC-negative, expression of interleukin-8 (IL-8) and IL-13 was increased (p=0.017 and p=0.045, respectively) if they were negative for progesterone receptor. In patients who died from their tumor, correlation between hormone receptor negativity and an increase in IL-4 was found. IL-5 was increased in patients with lymph node-positive and human epidermal growth factor receptor 2 (HER2)-positive disease (p=0.042). Moreover IL-4 was increased in patients with progesterone receptor-positive and estrogen receptor-negative status (p=0.024). Furthermore, the level of IL-6 was increased in patients with tumor grade G3 without progesterone receptor expression. CONCLUSION: Th2 cytokines are significantly modified in patients who are CTC-negative and progesterone receptor-positive. We suppose that an increase of IL-4 depends on hormone receptor status. In literature, a correlation between IL-4 and resistance to apoptosis is described. We suspect that IL-4 is responsible for the poor outcome of these cases.

FOXP3+ Cells Recruited by CCL22 into Breast Cancer Correlates with Less Tumor Nodal Infiltration.

BACKGROUND: Regulatory T-cells (Tregs) are a T-cell subpopulation with suppressive capacities, which are specifically attracted by C-C motif chemokine 22 (CCL22). Treg infiltration of tumors is associated with a poor prognosis in many patients. We aimed to investigate whether CCL22 is expressed in human breast cancer and whether its presence is associated with Treg infiltration. MATERIALS AND METHODS: Eighty paraffin-embedded human breast cancer samples were stained for CCL22 and for the Treg-specific transcription factor forkhead box P3 (FOXP3). Expression was evaluated in a semi-quantitative manner. RESULTS: FOXP3(+) cells infiltrated 50% of the breast tumors. Moreover, Treg infiltrated 93% of the tertiary lymphoid structures. CCL22 expression positively correlated with FOXP3(+) cell infiltration into the tertiary lymphoid structures. CONCLUSION: Our results demonstrate that CCL22 expression correlates with infiltration by FOXP3(+) cells. Interestingly, Treg presence negatively correlated with positive nodal status. In addition to their unfavorable role as mediators of evasion from antitumor immune response, Tregs might also have a beneficial role by reducing inflammation thereby limiting early tumor growth and spreading.

Expression of the Tumor-associated Mucin 1 Epitope Analyzed with the Humanized PankoMab-GEX™ Antibody in Malignant and Normal Tissues of the Head and Neck.

BACKGROUND: During neoplasia, glycosylation changes. In this setting, mucins, especially mucin 1 (MUC1), become carriers for oncofetal carbohydrates and relieve invasive growth. The recently described tumor-associated MUC1 epitope TA-MUC1 is primarily restricted to malignancies and is overexpressed in these tissues. The humanized monoclonal antibody PankoMab-GEX specifically recognizes TA-MUC1. MATERIALS AND METHODS: Laryngeal cancer specimens (n=125) and normal tissue of head and neck (n=7) were used in this study. Paraffin-embedded sections were incubated with PankoMab-GEX. Staining reaction was carried out using peroxidase (POD) labeling and diaminobenzidine (DAB). Breast cancer tissue was used as positive control and negative control used non-specific mouse IgM. Semi-quantitative evaluation by two independent double-blinded investigators, including a pathologist, used the immunoreactive score (IRS) of Remmele and Stegner. RESULTS: A total of 31 out of 125 laryngeal cancer specimens were classified as G1. Of these, 22 (71%) were completely negative for TA-MUC1, the remaining 9 showed very weak staining, with an IRS of 2. A total of 94 cases of cancer specimens were classified as G2 and G3; 34 of them were also negative, but 60 had an IRS of up to 9. All investigated normal tissue of the upper aerodigestive tract was completely negative for TA-MUC1. CONCLUSION: G1 tumors are completely negative or do not reach an IRS relevant range. The finding that G1 tumors are completely negative for TA-MUC1 or have IRS≤2 can be helpful for histopathological examination, especially concerning tumor grading. Therefore, this antibody holds great potential for use as a therapeutic antibody in laryngeal cancer.

Endometrial Adenocarcinoma: Analysis of Circulating Tumour Cells by RT-qPCR.

BACKGROUND: Endometrial adenocarcinoma is a frequently occurring cancer in women, accounting for 42,000 deaths every year. Despite treatment with standard therapy, occurrence of remote metastases and local recurrences is high. Through help of RT-qPCR minimal residual disease could be detected and characterized, facilitating therapeutic decision making. MATERIALS AND METHODS: A number of marker genes were first tested in model systems and genes that performed best, were consequently used for the examination of 13 blood samples from endometrial carcinoma patients. RESULTS: Cytokeratin 19 and MIG7 were chosen for the analysis in patient samples. Both genes were found up-regulated in small tumours and in one large tumour, but no statistical correlations could be revealed between expression levels of these two genes and tumour characteristics. CONCLUSION: There seems to be a coherence between gene expression and the stage of tumorigenesis, but the number of samples is still too small, to be able to obtain statistical significant differences.

New Marker Genes for Real-Time PCR-based Detection of Circulating Tumour Cells from Blood of Breast Cancer Patients.

BACKGROUND: The detection of circulating tumour cells (CTCs) from peripheral blood of cancer patients can be carried out by real-time PCR approaches using different gene expression levels of tumour cells and surrounding blood cells. MATERIALS AND METHODS: Potential marker genes were first analyzed in a model system and then applied to 20 blood samples of adjuvant breast cancer patients and gene expression levels were correlated to tumour characteristics. RESULTS: The mean of gene expression levels was found elevated for the four genes analyzed in the adjuvant breast cancer patient group in comparison to the samples of the group of healthy donors, but no correlation between gene expression and tumour characteristics could be detected as being statistically significant. CONCLUSION: The results demonstrated, that the employed methodology is functional, but has to be refined by certain approaches like simultaneously running a state-of-the-art system of CTC-detection comparing the results, and by an enlargement of patient collective and number of marker genes.

Immunocytochemical Characterization of Disseminated Tumour Cells from Bone Marrow of Breast Cancer Patients.

BACKGROUND: The occurrence of disseminated tumour cells in bone marrow of patients with breast cancer is linked to a worse prognosis. We present a method for DTC detection from bone marrow samples based on immunocytochemistry, using breast cancer-associated glycosylation molecules as markers for detection and characterization. MATERIALS AND METHODS: A double immunofluorescence staining of a pan-cytokeratin (CK) marker and either Tn or O-Acetyl-GD3 was carried out in artificial and patient bone marrow samples. RESULTS: The sample in which most cells stained positive for CK/Tn and CK/O-AC-GD3, was obtained from a patient who certainly had remote metastases. All other bone marrow samples showed heterogenous staining, so no correlation to tumour characteristics could be revealed. CONCLUSION: A certain characterization of tumour cells can be achieved by a double staining of bone marrow samples with CK and a glycosylation marker. For future studies, analysis should be extended to a larger patient collective and further examination of more glycosylation markers should be carried out.

The Presentation, Diagnosis, and Treatment of Sexually Transmitted Infections.

BACKGROUND: The reported incidence of sexually transmitted infections (STIs) in Germany is rising. For example, the number of new reported cases of syphilis rose from 3034 in 2010 to 4410 in 2012. METHODS: This review is based on pertinent articles retrieved by a selective search in MEDLINE, and on guidelines and systematic reviews from Germany and abroad. RESULTS: We discuss sexually transmitted infections presenting with genital, anal, perianal, or oral ulcers, urethritis, cervicitis, urethral or vaginal discharge, or genital warts. We also discuss sexually transmitted infection with HIV and the hepatitis C virus (HCV). Acquired sexually transmitted infections elevate the risk of transmission of other sexually transmitted infections; thus, patients presenting for the diagnosis or treatment of any kind of sexually transmitted infection should be evaluated for others as well. For most of these diseases, treatment of the patient's sexual partner(s) is indicated. Diagnostic nucleic acid amplification techniques are over 90% sensitive and specific and are generally the best way to detect the responsible pathogen. Factors impeding effective treatment include antibiotic resistance (an increasing problem) and the late diagnosis of HIV and HCV infections. CONCLUSION: Sexually transmitted infections are common around the world, and any such infection increases the patient's risk of contracting other types of sexually transmitted infection. Molecular genetic diagnostic techniques should be made widely available.

The role of TF- and Tn-antigens in breast cancer metastasis.

Almost 40 years ago, researchers found out that the Thomsen-Friedenreich (TF) and the Thomsen nouvelle (Tn) antigens could be detected in carcinoma, but not in healthy tissue. A short time after that it became clear that TF and Tn are precursor molecules of the MN-blood group antigens. In normal tissue TF and Tn are coated by glycosyl structures, thereby forming the glycoproteins which are known to account for the MN-blood group, but in malignant tissue these molecules are uncovered.TF, which has an additional Galectin-residue compared to Tn, is correlated with a more favourable prognosis for patients. On the contrary, patients with Tn-bearing tissues have a worse prognosis for overall and progression-free survival. It is known that TF and Tn are involved in the adhesion of tumour cells to the endothelium via a mechanism recruiting Galectin-3 and MUC-1, which is the first step in metastasis formation. Furthermore, it became clear that this pathway can be blocked by a growing number of molecules, thereby creating ways of therapeutical intervention.