BackgroundThere is partially conflicting evidence on the influence of the steroid hormones estrogen (E) and progesterone (P) on the development of ovarian cancer (OC). The aim of this study was to assess the expression of the receptor isoforms ER-α/-β and PR-A/-B in OC tissue and to analyze its impact on clinical and pathological features and patient outcome.Methods155 OC patients were included who had been diagnosed and treated between 1990 and 2002. Patient characteristics, histology and follow-up data were available. ER-α/-β and PR-A/-B expression were determined by immunohistochemistry.ResultsOC tissue was positive for ER-α/-β in 31.4% and 60.1% and PR-A/-B in 36.2% and 33.8%, respectively. We identified significant differences in ER-β expression related to the histological subtype (p=0.041), stage (p=0.002) and grade (p=0.011) as well as PR-A and tumor stage (p=0.03). Interestingly, median receptor expression for ER-α and PR-A/-B was significantly higher in G1 vs. G2 OC. Kaplan Meier analysis revealed a good prognosis for ER-α positive (p=0.039) and PR-B positive (p<0.001) OC. In contrast, ER-β negative OC had a favorable outcome (p=0.049). Besides tumor grade and stage, Cox-regression analysis showed PR-B to be an independent prognostic marker for patient survival (p=0.009, 95% CI 0.251-0.823, HR 0.455).ConclusionER-α/-β and PR-A/-B are frequently expressed in OC with a certain variability relating to histological subtype, grade and stage. Univariate analysis indicated a favorable outcome for ER-α positive and PR-B positive OC, while multivariate analysis showed PR-B to be the only independent prognostic marker for patient survival. In conclusion, ER and PR receptors may be useful targets for a more individualized OC therapy.

al. Transforming growth factor beta1 regulates melanocyte proliferation and differentiation in mouse neural crest cells via stem cell factor ⁄ KIT signaling.Sir: As ovaries are the target organs of gonadotropins, a relationship with the development or growth of ovarian cancer has been postulated. 1 However, there are few data, obtained with small patient numbers, for folliclestimulating hormone (FSH) receptor (FSH-R) and luteinizing hormone (LH) receptor (LH-R) expression in ovarian cancer tissue, and hardly any data on their prognostic relevance. Therefore, we conducted this study to quantify LH-R and FSH-R expression in ovarian cancer tissue and to analyse their impact on relapse and survival.Immunohistochemical (IHC) staining was performed for LH-R and FSH-R expression in 156 ovarian cancer tissue samples. Most patients presented with advanced Table 1. Patient characteristics Patients (n) 156 Age at primary diagnosis (a) [years (range)] 58 (18-88) Histology (%) Serous 70.5 Mucinous 13.5 Endometrioid 7.7 Clear cell 8.3 Tumour grading (%) Low grade 27.2 Intermediate 36.5 High grade 36.3 Tumor stage (FIGO) (%) I 22.6 II 5.8 III 70.3 IV 1.3 Median follow-up time (a) [years (range)] 7.3 (0.3-16.8) Median relapse-free survival (a) [years (range)] 2.1 (0.9-7.2) Median overall survival (a) [years (range)] 5.9 (0.3-16.6)

Hand osteoarthritis (OA) is a common degenerative joint disorder leading to substantial pain and disability. The most severe subtype is erosive hand OA characterized by an abrupt onset, local inflammation, subchondral erosions and worse outcomes than non-erosive disease. Biomarkers of hand OA could help to diagnose the disease earlier, to distinguish patients with erosive and non-erosive forms, to assess disease severity or to predict its future progression. The objective of this review was to summarize the role of potential biomarkers of hand OA. A PubMed search for soluble biomarkers associated with hand OA was performed from inception to June 2017. In total, 21 relevant publications were found and reviewed. These publications identified 20 potential biomarkers of hand OA. C-terminal cross-linking telopeptide of type II collagen, cartilage oligomeric matrix protein, osteocalcin, hyaluronan, urinary pentosidine, vascular cell adhesion molecule 1, monocyte chemotactic protein 1, osteoprotegerin and interleukin 1 have been shown as potential biomarkers for assessing disease severity. C-terminal cross-linking telopeptide of type I collagen, hyaluronan, urinary pentosidine and myeloperoxidase were shown to differentiate between erosive and non-erosive hand OA patients. A number of biomarkers reflecting joint tissue metabolism and inflammation have been studied in hand OA. Some were identified as potential biomarkers of disease severity and progression, others were shown to differentiate between erosive and non-erosive disease. However, further research is necessary to assess the value of biomarkers for use in clinical practice.

BackgroundClusterin (apolipoprotein J) is an extracellular chaperone involved in the number of biological processes, such as inflammation and apoptosis. Recent data suggest its protective role in autoimmune diseases. The aim of this study was to analyse the serum levels of clusterin and its expression in skeletal muscle specimens in patients with idiopathic inflammatory myopathies (IIM) vs healthy controls, and to investigate the association of clusterin with disease activity.Materials and methodsClusterin serum levels were measured by ELISA (Biovendor) in 65 patients with IIM (27 dermatomyositis (DM), 28 polymyositis (PM), 10 immune-mediated necrotizing myopathy (IMNM)) and in 54 healthy individuals. Clusterin mRNA expression was analysed in skeletal muscle samples obtained from muscle biopsy (mini-invasive Bergstrom technique) in 10 patients with IIM (DM/PM) and 10 healthy controls by RT-PCR. Disease activity was assessed using myositis disease activity assessment visual analogue scales (MYOACT), myositis intention to treat index (MITAX), health assessment questionnaire (HAQ) and global disease assessment evaluated by patient and doctor. Data are presented as mean ± SD.ResultsSerum concentrations of clusterin were significantly higher in all patients with IIM compared with healthy controls (87.1±22.8 vs 68.4±12.4, p<0.0001). There were no differences in the clusterin levels among particular myositis subtypes. Clusterin levels in all IIM patients positively correlated with MITAX (r=0.357, p=0.004), MYOACT (r=0.337, p=0.008) and doctor global disease assessment (r=0.309, p=0.015), but not with muscle enzymes. Moreover, mRNA expression of clusterin in muscle tissues was almost three-times higher in patients with IIM than in healthy individuals (p=0.029).ConclusionsWe demonstrate here for the first time increased clusterin expression in myositis patients than in healthy subjects and its association with clinical disease activity.AcknowledgementSupported by the project of MHCR for conceptual development of research organisation 00023728 and project NV16-33746A.

BackgroundClusterin (also known as apolipoprotein J) is a molecular chaperone that participates in inflammatory and apoptotic processes. Recent data indicate its possible protective role in the development of chronic autoimmune disorders.ObjectivesThe aim of this study was to analyse the skeletal muscle expression of clusterin and its serum levels in patients with idiopathic inflammatory myopathies (IIM) and in healthy donors, and to examine the association of clusterin with disease activity.MethodsClusterin mRNA expression in skeletal muscle specimens, obtained by muscle biopsy (mini-invasive Bergstrom technique), was determined using qPCR in 10 patients with IIM and 10 healthy subjects. Serum concentrations of clusterin were measured by ELISA (Biovendor) in 65 patients with IIM (27 dermatomyositis (DM), 28 polymyositis (PM), 10 immune-mediated necrotizing myopathy (IMNM)) and in 54 healthy individuals. Disease activity was assessed using myositis intention to treat index (MITAX), myositis disease activity assessment visual analogue scales (MYOACT), health assessment questionnaire (HAQ) and global disease assessment evaluated by doctor and patient. Data are presented as mean ± SD.ResultsClusterin mRNA expression in skeletal muscles was increased in patients with IIM compared to healthy donors (p=0.029). In addition, serum clusterin levels were significantly higher in all IIM patients than in healthy subjects (87.1±22.8 vs 68.4±12.4, p<0.0001) and also in individual subsets of patients in comparison to the control group (DM: 87.7±24.7, PM: 86.1±23.2, IMNM: 88.15±18.0, p<0.0001 for all). Clusterin levels in all patients with IIM positively correlated with MYOACT (r=0.337, p=0.008), MITAX (r=0.357, p=0.004) and global disease assessment evaluated by doctor (r=0.309, p=0.015). In patients with DM, positive correlations with MYOACT (r=0.499, p=0.009), MITAX (r=0.491, p=0.009), HAQ (r=0.470, p=0.014), global disease assessment evaluated by doctor (r=0.559, p=0.004), γ-glutamyl transpeptidase and asparate aminotransferase were found (r=0.504, p=0.007; r=0.429, p=0.025, respectively). PM and IMNM subsets showed no significant association.ConclusionsWe demonstrate increased local and systemic expression of clusterin in IIM patients compared to healthy individuals and its association with disease activity, especially in dermatomyositis.AcknowledgementsSupported by the project of MHCR for conceptual development of research organization 00023728 and project NV16–33746A.Disclosure of InterestNone declared