Tumoral programmed cell death 1 (PD1) expression in endometrial carcinoma is a prognostic marker for patient outcome.

Objective: Immune checkpoint inhibitors have recently demonstrated benefit in patients with advanced and recurrent endometrial carcinoma. This retrospective study investigated immune checkpoint molecules in endometrial carcinoma as they pertain to the molecular subtypes, clinical outcomes, and predictive value.

Methods: Tumoral RNA expression of genes controlling the immune checkpoint, programmed cell death 1 (PD1, encoded by ), its ligand (PDL1, encoded by ), and interferon gamma () was determined in 239 endometrial carcinoma tissues by quantitative polymerase chain reaction (qPCR) and compared with endometrial tissue from 25 controls.

Crystallization of mixtures of local anesthetics with and without select adjuvants: a semiquantitative light microscopy analysis.

Introduction: Injecting mixtures of local anesthetics with or without adjuvants is a common practise in regional and particularly obstetric anesthesia to decrease block onset time and/or augment epidural analgesia for cesarean section. While evidence on the efficacy of this practise is equivocal, little is known about its safety in terms of the pharmacologic compatibility of local anesthetics.

Methods: We assessed the grade of crystallization in individual mixtures of seven local anesthetics (bupivacaine, ropivacaine, lidocaine, procaine, chloroprocaine, mepivacaine, prilocaine) with or without four adjuvants (sodium bicarbonate, dexamethasone, clonidine, fentanyl) using a semiquantitative light microscopy scale (ranging from 0 to 5), repeatedly for up to 60 min and performed correlation analysis between grade of crystallization and initial solution pH.

A comparison of four technologies for detecting p53 aggregates in ovarian cancer.

The tumor suppressor protein p53 is mutated in half of all cancers and has been described to form amyloid-like structures, commonly known from key proteins in neurodegenerative diseases. Still, the clinical relevance of p53 aggregates remains largely unknown, which may be due to the lack of sensitive and specific detection methods. The aim of the present study was to compare the suitability of four different methodologies to specifically detect p53 aggregates: co-immunofluorescence (co-IF), proximity ligation assay (PLA), co-immunoprecipitation (co-IP), and the p53-Seprion-ELISA in cancer cell lines and epithelial ovarian cancer tissue samples.

A retrospective validation of CanAssist Breast in European early-stage breast cancer patient cohort.

CanAssist Breast (CAB), a prognostic test uses immunohistochemistry (IHC) approach coupled with artificial intelligence-based machine learning algorithm for prognosis of early-stage hormone-receptor positive, HER2/neu negative breast cancer patients. It was developed and validated in an Indian cohort. Here we report the first blinded validation of CAB in a multi-country European patient cohort.

Influence of Pregnancy-Related Conditions on Human Epididymis Protein 4 Serum Levels in Comparison to CA 125 - a Prospective Cohort Trial.

HE4 and CA 125, two established biomarkers for assessing adnexal masses in non-pregnant women, are hardly investigated in pregnancy, especially in pregnancy-associated conditions. The aim was to evaluate HE4 and CA 125 levels in the course of pregnancy and to assess the impact of pregnancy disorders, contractions and rupture of membranes on HE4 and CA 125 serum levels in order to use these parameters for evaluation of adnexal masses in pregnancy. Blood samples (n = 238) of 201 women seen at the Medical University of Innsbruck, Austria, were prospectively obtained during pregnancy and postpartum.

Clinical impact of EZH2 and its antagonist SMARCA4 in ovarian cancer.

SMARCA4 and EZH2 are two functional key players of their respective antagonizing chromatin remodeling complexes SWI/SNF and PRC2. EZH2 inhibitory drugs may abrogate pro-oncogenic features of PRC2 and turn the balance to cell differentiation via SWI/SNF activity in cancers. SMARCA4 and EZH2 expression was assessed by RT-PCR in 238 epithelial ovarian cancers (OCs) and put in relation to clinico-pathological parameters and patients' outcome.

High RIG-I expression in ovarian cancer associates with an immune-escape signature and poor clinical outcome.

Ovarian cancer (OC) is the most lethal gynecological malignancy, with platinum-based chemotherapy remaining the mainstay for adjuvant treatment after surgery. The lack of indication for immunotherapy may at least in part result from the lack of suitable biomarkers allowing stratification of potentially responding patients. In this monocentric study of 141 cases with OC, we used real-time quantitative PCR to assess the expression of retinoic acid-inducible gene-I (RIG-I) in primary tumor and healthy ovarian control tissues.

Glucocorticoid Receptor-Deficient Foxp3 Regulatory T Cells Fail to Control Experimental Inflammatory Bowel Disease.

Activation of the immune system increases systemic adrenal-derived glucocorticoid (GC) levels which downregulate the immune response as part of a negative feedback loop. While CD4 T cells are essential target cells affected by GC, it is not known whether these hormones exert their major effects on CD4 helper T cells, CD4Foxp3 regulatory T cells (Treg cells), or both. Here, we generated mice with a specific deletion of the glucocorticoid receptor (GR) in Foxp3 Treg cells.

NADPH oxidase 4 expression in the normal endometrium and in endometrial cancer.

The aim of this study was to explore the role of NOX4 in the biology of the normal endometrium and endometrial cancer. NOX4 plays a key role in other adenocarcinomas and has been implicated in the pathogenesis of diabetes and obesity, which are important risk factors for endometrial cancer. NOX4 expression was assessed in 239 endometrial cancer and 25 normal endometrium samples by quantitative real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry.

Correction to: Epigenetic regulation of L1CAM in endometrial carcinoma: comparison to cancer-testis (CT-X) antigens.

Following publication of the original article [1], we have been alerted to errors in Figs. 2 and 8. In Fig.

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality.

Breast cancer remains a leading cause of morbidity and mortality worldwide yet methods for early detection remain elusive. We describe the discovery and validation of biochemical signatures measured by mass spectrometry, performed upon blood samples from patients and controls that accurately identify (>95%) the presence of clinical breast cancer. Targeted quantitative MS/MS conducted upon 1225 individuals, including patients with breast and other cancers, normal controls as well as individuals with a variety of metabolic disorders provide a biochemical phenotype that accurately identifies the presence of breast cancer and predicts response and survival following the administration of neoadjuvant chemotherapy.

Evaluation of Vav3.1 as prognostic marker in endometrial cancer.

Purpose: Vav3 is a guanine nucleotide exchange factor that regulates the activity of Rho/Rac family GTPases. In a study on ovarian cancer, we recently demonstrated pronounced prognostic and predictive value of Vav3.1, a specific truncation variant of the parental Vav3 gene.

Development of a novel prognostic score for breast cancer patients using mRNA expression of CHAC1.

Aim: To develop a prognostic score for primary breast cancer patients integrating conventional predictors and the novel biomarker CHAC1 to aid adjuvant chemotherapy decisions.

Patients & Methods: A prognostic score for overall survival was developed using: conventional predictors from a dataset of 1777 patients and the weight of CHAC1 mRNA expression from an independent dataset of 106 patients using multivariate Cox regression.

Results: The new score includes: CHAC1 mRNA expression, age, tumor size, HER2 neu status, lymph node status and degree of malignancy.

Methylome analysis of extreme chemoresponsive patients identifies novel markers of platinum sensitivity in high-grade serous ovarian cancer.

Background: Despite an early response to platinum-based chemotherapy in advanced stage high-grade serous ovarian cancer (HGSOC), the majority of patients will relapse with drug-resistant disease. Aberrant epigenetic alterations like DNA methylation are common in HGSOC. Differences in DNA methylation are associated with chemoresponse in these patients.

Evaluating L1CAM expression in human endometrial cancer using qRT-PCR.

Background: Management of endometrial carcinoma (EC) still needs improvement of risk assessment. Recently, L1CAM immunohistochemical (IHC) evaluation showed a unique value to predict the outcome of early EC. However IHC results are often conflicting for lack of inter-laboratory standardisation.

Reduced mRNA expression levels of NFE2L2 are associated with poor outcome in breast cancer patients.

Background: The transcription factor nuclear factor erythroid 2-related factor 2 (NFE2L2; previously known as NRF2) is a crucial regulator of the intracellular antioxidant response. It controls the expression of genes involved in the detoxification and elimination of reactive oxidants and electrophilic agents. The role of NFE2L2 in cancer is subject of controversial discussion, as it has been reported to have both pro-and anti-tumourigenic functions.

Evaluation of folate receptor 1 (FOLR1) mRNA expression, its specific promoter methylation and global DNA hypomethylation in type I and type II ovarian cancers.

Background: In this retrospective study we evaluated the respective correlations and clinical relevance of FOLR1 mRNA expression, FOLR1 promoter specific methylation and global DNA hypomethylation in type I and type II ovarian cancer.

Methods: Two hundred fifty four ovarian cancers, 13 borderline tumours and 60 samples of healthy fallopian epithelium and normal ovarian epithelium were retrospectively analysed for FOLR1 expression with RT-PCR. FOLR1 DNA promoter methylation and global DNA hypomethylation (measured by means of LINE1 DNA hypomethylation) were evaluated with MethyLight technique.

High prevalence of side population in human cancer cell lines.

Cancer cell lines are essential platforms for performing cancer research on human cells. We here demonstrate that, across tumor entities, human cancer cell lines harbor minority populations of putative stem-like cells, molecularly defined by dye extrusion resulting in the side population phenotype. These findings establish a heterogeneous nature of human cancer cell lines and argue for their stem cell origin.

Clinical impact of L1CAM expression measured on the transcriptome level in ovarian cancer.

Background: High expression of L1 cell adhesion molecules (L1CAM) has been repeatedly shown to be associated with aggressive disease behavior, which translates in poor clinical outcome in various cancer entities. However, in ovarian cancer results based either on immunohistochemistry or cytosolic protein quantifications remained conflicting regarding clinical behavior. In the present work we assessed L1CAM expression on the transcriptome level with the highly sensitive quantitative real-time PCR (qRT-PCR) to define its relevance in ovarian cancer biology.

Expression and promotor hypermethylation of miR-34a in the various histological subtypes of ovarian cancer.

Background: An increasing body of evidence shows that miR-34 family has tumor suppressive properties mediating apoptosis, cell cycle arrest and senescence. In ovarian cancer, miR34 family members were found to be under expressed. Particularly miR-34a has been revealed to be a direct transcriptional target of p53 which is frequently mutated in epithelial ovarian carcinomas especially in high grade serous cancer.

HOTAIR and its surrogate DNA methylation signature indicate carboplatin resistance in ovarian cancer.

Background: Understanding carboplatin resistance in ovarian cancer is critical for the improvement of patients' lives. Multipotent mesenchymal stem cells or an aggravated epithelial to mesenchymal transition phenotype of a cancer are integrally involved in pathways conferring chemo-resistance. Long non-coding RNA HOTAIR (HOX transcript antisense intergenic RNA) is involved in mesenchymal stem cell fate and cancer biology.

Detection of soluble EpCAM (sEpCAM) in malignant ascites predicts poor overall survival in patients treated with catumaxomab.

EpCAM is an attractive target for cancer therapy and the EpCAM-specific antibody catumaxomab has been used for intraperitoneal treatment of EpCAM-positive cancer patients with malignant ascites. New prognostic markers are necessary to select patients that mostly benefit from catumaxomab. Recent data showed that soluble EpCAM (sEpCAM) is capable to block the effect of catumaxomab in vitro.

High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing.

Screening for founder mutations in BRCA1 and BRCA2 has been discussed as a cost-effective testing strategy in certain populations. In this study, comprehensive BRCA1 and BRCA2 testing was performed in a routine diagnostic setting. The prevalence of the BRCA1 stop mutation c.