Gene expression markers in peripheral blood and outcome in patients with platinum-resistant ovarian cancer: A study of the European GANNET53 consortium.

Disease progression is a major problem in ovarian cancer. There are very few treatment options for patients with platinum-resistant ovarian cancer (PROC), and therefore, these patients have a particularly poor prognosis. The aim of the present study was to identify markers for monitoring the response of 123 PROC patients enrolled in the Phase I/II GANNET53 clinical trial, which evaluated the efficacy of Ganetespib in combination with standard chemotherapy versus standard chemotherapy alone. In total, 474 blood samples were collected, comprising baseline samples taken before the first administration of the study drugs and serial samples taken during treatment until further disease progression (PD). After microfluidic enrichment, 27 gene transcripts were analyzed using quantitative polymerase chain reaction and their utility for disease monitoring was evaluated. At baseline, ERCC1 was associated with an increased risk of PD (hazard ratio [HR] 1.75, 95% confidence interval [CI]: 1.20-2.55; p = 0.005), while baseline CDH1 and ESR1 may have a risk-reducing effect (CDH1 HR 0.66, 95% CI: 0.46-0.96; p = 0.024; ESR1 HR 0.58, 95% CI: 0.39-0.86; p = 0.002). ERCC1 was observed significantly more often (72.7% vs. 53.9%; p = 0.032) and ESR1 significantly less frequently (59.1% vs. 78.3%; p = 0.018) in blood samples taken at radiologically confirmed PD than at controlled disease. At any time during treatment, ERCC1-presence and ESR1-absence were associated with short PFS and with higher odds of PD within 6 months (odds ratio 12.77, 95% CI: 4.08-39.97; p < 0.001). Our study demonstrates the clinical relevance of ESR1 and ERCC1 and may encourage the analysis of liquid biopsy samples for the management of PROC patients.

Prognostic significance of circulating tumor cells and tumor related transcripts in small cell lung cancer: A step further to clinical implementation.

Small-cell lung cancer (SCLC) is a fatal disease with limited treatment options. Circulating tumor cells (CTCs) in liquid biopsy samples may serve as predictive and prognostic biomarkers; but the analysis of CTCs is still challenging. By using microfluidic or density gradient CTC enrichment in combination with immunofluorescent (IF) staining or qPCR of CTC-related transcripts, we achieved a 60.8% to 88.0% positivity in SCLC blood samples. Epithelial and neuroendocrine transcripts including the druggable target DLL3 were associated with shorter overall survival (OS), indicating the clinical value of these markers in terms of differential diagnosis and treatment decisions. High CTC counts and the presence of CTC duplets detected by IF staining were prognostic for OS, and thus may serve as indicators of disease progression or therapy failure. In patient samples with high CTC load detected by IF staining, a concordance of the transcripts positivity in circulating free plasma RNA and CTCs was observed. Our data emphasize the role of CTCs and CTC-related transcripts and underline the clinical value of liquid biopsy analysis in SCLC.

Association of Four Interleukin-8 Polymorphisms (-251 A>T, +781 C>T, +1633 C>T, +2767 A>T) with Ovarian Cancer Risk: Focus on Menopausal Status and Endometriosis-Related Subtypes.

Interleukin-8 (IL-8) is involved in the regulation of inflammatory processes and carcinogenesis. Single-nucleotide polymorphisms (SNPs) within the IL-8 gene have been shown to alter the risks of lung, gastric, or hepatocellular carcinomas. To date, only one study examined the role of IL-8 SNPs in ovarian cancer (OC), suggesting an association between two IL-8 SNPs and OC risk. In this study, we investigated four common IL-8 SNPs, rs4073 (-251 A>T), rs2227306 (+781 C>T), rs2227543 (+1633 C>T), and rs1126647 (+2767 A>T), using the restriction fragment length polymorphism (PCR-RFLP) technique. Our study included a cohort of 413 women of Central European descent, consisting of 200 OC patients and 213 healthy controls. The most common (73.5%) histological type was high-grade serous OC (HGSOC), whereas 28/200 (14%) patients had endometriosis-related (clear cell or endometrioid) OC subtypes (EROC). In postmenopausal women, three of the four investigated SNPs, rs4073 (-251 A>T), rs2227306 (+781 C>T), and rs2227543 (+1633 C>T), were associated with OC risk. Furthermore, we are the first to report a significant relationship between the T allele or TT genotype of SNP rs1126647 (+2767 A>T) and the EROC subtype (p = 0.02 in the co-dominant model). The TT homozygotes were found more than twice as often in EROC compared to other OC subtypes (39% vs. 19%, p = 0.015). None of the examined SNPs appeared to influence OC risk in premenopausal women, nor were they associated with the aggressive HGSOC subtype or the stage of disease at the initial diagnosis.

Amyloid-like p53 as prognostic biomarker in serous ovarian cancer-a study of the OVCAD consortium.

TP53 is the most commonly mutated gene in cancer and has been shown to form amyloid-like aggregates, similar to key proteins in neurodegenerative diseases. Nonetheless, the clinical implications of p53 aggregation remain unclear. Here, we investigated the presence and clinical relevance of p53 aggregates in serous ovarian cancer (OC). Using the p53-Seprion-ELISA, p53 aggregates were detected in 46 out of 81 patients, with a detection rate of 84.3% in patients with missense mutations. High p53 aggregation was associated with prolonged progression-free survival. We found associations of overall survival with p53 aggregates, but they did not reach statistical significance. Interestingly, p53 aggregation was significantly associated with elevated levels of p53 autoantibodies and increased apoptosis, suggesting that high levels of p53 aggregates may trigger an immune response and/or exert a cytotoxic effect. To conclude, for the first time, we demonstrated that p53 aggregates are an independent prognostic marker in serous OC. P53-targeted therapies based on the amount of these aggregates may improve the patient's prognosis.

Comparison of RNA Marker Panels for Circulating Tumor Cells and Evaluation of Their Prognostic Relevance in Breast Cancer.

Liquid biopsy is a promising tool for therapy monitoring of cancer patients, but a need for further research in this field exists in order to improve sensitivity, specificity, standardization and minimize costs. In our present study, we evaluated two panels of transcripts related with the presence of circulating tumor cells (CTCs) (Panel 1: CK19, EpCAM, SCGB2A2 and Panel 2: EMP2, SLC6A8, HJURP, MAL2, PPIC and CCNE2) in two cohorts of breast cancer patients (metastatic and early). A blood cell fraction possibly containing CTCs was isolated with density gradient centrifugation, followed by RNA isolation and qPCR using TaqMan® or RT-qPCR using hybridization probes. The positivity rates of the investigated panels were similar, albeit higher in metastatic (69.4% Panel 1, 75.0% Panel 2; total 86.1%) compared to early (18.9% Panel 1, 23.3% Panel 2; total 31.1%) breast cancer patients. CK19, SCGB2A2, EMP2, HJURP, MAL2, and CCNE2 individually correlated with shorter overall survival in the metastatic patient cohort. The findings highlight the additional value of Panel 2 markers, which are in contrast to CK19 and EpCAM not solely linked to an epithelial phenotype.

Effect of short-term storage of blood samples on gene expression in lung cancer patients.

OBJECTIVES: The stability of gene transcripts associated with the presence of circulating tumor cells (CTCs) has been predominantly studied in cultured cancer cell lines added to blood samples under artificial conditions. In the present study the effect of storage on CTC-related transcripts was assessed in blood samples taken from patients with non-small lung cancer (n=58). METHODS: The blood samples were split in two equal parts to compare the gene expression with and without storage for 24 h at ambient temperature without preservative added. After enrichment using the microfluidic Parsortix® technology, the expression levels of selected genes were assessed using quantitative PCR following a gene-specific pre-amplification. The prognostic relevance of each gene in fresh and stored blood samples was evaluated using the R-package Survminer. RESULTS: Some genes were either not affected (TWIST1, CDH5, CK19) or upregulated upon storage (NANOG, MET, UCHL1) but still associated with poor prognosis. In contrast, ERBB3, PTHLH, EpCAM, and TERT were no longer associated with the overall survival of the patients. CONCLUSIONS: The study demonstrates the surprising stability of CTC-related transcripts, which makes overnight shipping of native blood samples possible. Careful verification is required when using model systems - such as normal blood spiked with tumor cells - or other CTC-related markers, as individual transcripts may respond differently to storage.

Comparison of microfluidic platforms for the enrichment of circulating tumor cells in breast cancer patients.

PURPOSE: Circulating tumor cells (CTCs) hold promise to be a non-invasive measurable biomarker in all cancer stages. Because the analysis of CTCs is still a technical challenge, we compared different types of microfluidic enrichment protocols to isolate these rare cells from the blood. METHODS: Blood samples from patients with early and metastatic breast cancer (BC) were processed using the microfluidic Parsortix® technology employing (i) a single-step cell separation using the standard GEN3D6.5 microfluidic cassette, (ii) a two-step separation with an upfront pre-enrichment, and (iii) a two-step separation with a different type of cassette. In the enriched cells, the gene expression levels of CTC-related transcripts were assessed using quantitative real-time PCR (qPCR) by Taqman® and Lightcycler (LC) technology. RESULTS: 23/60 (38.3%) BC samples were assigned as positive due to the presence of at least one gene marker beyond the threshold level. The prevalence of epithelial markers was significantly higher in metastatic compared to early BC (EpCAM: 31.3% vs. 7.3%; CK19: 21.1% vs. 2.4%). A high level of concordance was observed between CK19 assessed by Taqman® and LC technology, and for detection of the BC-specific gene SCGB2A2. An upfront pre-enrichment resulted in lower leukocyte contamination, at the cost of fewer tumor cells captured. CONCLUSION: The Parsortix® system offers both reasonable recovery of tumor cells and depletion of contaminating leukocytes when the single-step separation using the GEN3D6.5 cassette is employed. Careful selection of suitable markers and cut-off thresholds is an essential point for the subsequent molecular analysis of the enriched cells.

Cancer Stem Cell-Like Circulating Tumor Cells Are Prognostic in Non-Small Cell Lung Cancer.

Despite recent advances in the treatment of non-small cell lung cancer (NSCLC), less than 10% of patients survive the first five years when the disease has already spread at primary diagnosis. METHODS: Blood samples were taken from 118 NSCLC patients at primary diagnosis or at progression of the disease before the start of a new treatment line and enriched for circulating tumor cells (CTCs) by microfluidic Parsortix™ (Angle plc, Guildford GU2 7AF, UK) technology. The gene expression of epithelial cancer stem cell (CSC), epithelial to mesenchymal (EMT), and lung-related markers was assessed by qPCR, and the association of each marker with overall survival (OS) was evaluated using log-rank tests. RESULTS: EpCAM was the most prevalent transcript, with 53.7% positive samples at primary diagnosis and 25.6% at recurrence. EpCAM and CK19, as well as NANOG, PROM1, TERT, CDH5, FAM83A, and PTHLH transcripts, were associated with worse OS. However, only the CSC-specific NANOG and PROM1 were related to the outcome both at primary diagnosis (NANOG: HR 3.21, 95%CI 1.02-10.14, p = 0.016; PROM1: HR 4.23, 95% CI 0.65-27.56, p = 0.007) and disease progression (NANOG: HR 4.17, 95%CI 0.72-24.14, p = 0.025; PROM1: HR 4.77, 95% CI 0.29-78.94, p = 0.032). CONCLUSIONS: The present study further underlines the relevance of the molecular characterization of CTCs. Our multi-marker analysis highlighted the prognostic value of cancer stem cell-related transcripts at primary diagnosis and disease progression.

[Erratum to: Strategy for university emergency room management at the beginning of an epidemic using COVID-19 as an example]. / Erratum zu: Strategie einer universitären Notaufnahme für das COVID-19-Management im Rahmen einer beginnenden Epidemie.

[This corrects the article DOI: 10.1007/s10049-020-00759-8.].

[Strategy for university emergency room management at the beginning of an epidemic using COVID-19 as an example]. / Strategie einer universitären Notaufnahme für das COVID-19-Management im Rahmen einer beginnenden Epidemie.

Due to the increasing number of COVID-19 infections worldwide, all hospitals are faced with the challenge associated with the pandemic. In particular, emergency rooms must prepare and implement completely new workflows. This applies in particular to patient screening and selection (triage). Close cooperation with other specialist areas such as hygiene, infectiology or virology is also necessary in order to implement appropriate treatment concepts before, during and after the diagnosis is completed. In addition, communication and quality and risk management are highly relevant in addition to the clinical aspects. This article uses COVID-19 as an example to describe how emergency rooms can prepare for a pandemic.

Molecular Characterization of Circulating Tumor Cells Enriched by A Microfluidic Platform in Patients with Small-Cell Lung Cancer.

At initial diagnosis, most patients with small-cell lung cancer (SCLC) present with metastatic disease with a high number of tumor cells (CTCs) circulating in the blood. We analyzed RNA transcripts specific for neuroendocrine and for epithelial cell lineages, and Notch pathway delta-like 3 ligand (DLL3), the actionable target of rovalpituzumab tesirine (Rova-T) in CTC samples. Peripheral blood samples from 48 SCLC patients were processed using the microfluidic Parsortix™ technology to enrich the CTCs. Blood samples from 26 healthy donors processed in the same way served as negative controls. The isolated cells were analyzed for the presence of above-mentioned transcripts using quantitative PCR. In total, 16/51 (31.4%) samples were CTC-positive as determined by the expression of epithelial cell adhesion molecule 1 (EpCAM), cytokeratin 19 (CK19), chromogranin A (CHGA), and/or synaptophysis (SYP). The epithelial cell lineage-specific EpCAM and/or CK19 gene expression was observed in 11 (21.6%) samples, and positivity was not associated with impaired survival. The neuroendocrine cell lineage-specific CHGA and/or SYP were positive in 13 (25.5%) samples, and positivity was associated with poor overall survival. DLL3 transcripts were observed in four (7.8%) SCLC blood samples and DLL3-positivity was similarly associated with poor overall survival (OS). CTCs in SCLC patients can be assessed using epithelial and neuroendocrine cell lineage markers at the molecular level. Thus, the implementation of liquid biopsy may improve the management of lung cancer patients, in terms of a faster diagnosis, patient stratification, and on-treatment therapy monitoring.

The 811 C/T polymorphism in the 3' untranslated region of the selenoprotein 15-kDa (Sep15) gene and breast cancer in Caucasian women.

The 15-kDa selenoprotein (Sep15) is a selenocysteine-containing oxidoreductase in the endoplasmic reticulum that participates in disulfide-bond formation and protein folding control. The 3'-untranslated region (3'-UTR) contains two exclusively linked, polymorphic sites at positions 811 (C/T) and 1125 (G/A), which result in two functional haplotypes: 811C/1125G or 811T/1125A. The 811T/1125A variant occurs significantly more often in African-Americans as compared to Caucasians and has been linked to increased breast cancer risk in black women. We studied the 811C/T (rs5845) Sep15 gene polymorphism in 182 Caucasian women-83 breast cancer cases and 99 healthy controls-by pyrosequencing and polymerase chain reaction. Associations between allelic variants and clinico-pathological variables (e.g., age, stage of disease, tumor type, grading, and receptor status) were investigated. The genotype distribution in breast cancer patients (CC 63.9 %, CT 33.7 %, TT 2.4 %) and controls (69.7 %, CT 28.3 %, TT 2 %) showed no significant difference (OR 0.77, 95 % CI 0.41-1.42, p = 0.4). The overall low prevalence of the T allele was in accordance with that reported for Caucasians in previous studies. There was no significant association between 811C/T Sep15 polymorphism and any of clinico-pathological parameters. In conclusion, we are the first to report on 811C/T SEP 15 polymorphism in white breast cancer patients. Genotype variation within the 3'-UTR of the SEP 15 gene showed no association with breast cancer risk or clinico-pathological parameters in Caucasian women.

Association of HER2 codon 655 polymorphism with ovarian cancer.

The role of the human epidermal growth factor receptor 2 (HER2) codon 655 (Ile655Val) polymorphism in ovarian cancer is not fully understood. Two studies indicated a possible association between the Val allele and elevated risk or reduced prognosis of ovarian cancer. We investigated the HER2 codon 655 (rs1136201) polymorphism in 242 Austrian women-142 ovarian cancer patients and 100 healthy controls-by polymerase chain reaction and pyrosequencing. Associations between Ile655Val polymorphism and clinicopathological variables (e.g., age, FIGO stage, grading, serous vs. non-serous histology) were evaluated. The genotype distributions in ovarian cancer patients and controls were: AA; 66.2 %, AG; 25.35 %, GG; 8.45 %, and AA; 63 %, AG; 34 %, GG; 3.7 %, respectively (OR 1.15, CI 95 % 0.67-1.96). We observed a non-significant trend toward elevated cancer risk in Val/Val genotype (OR 2.98, CI 95 % 0.82-10.87, p = 0.10). Of note, 11 out of 12 Val/Val homozygotes were postmenopausal. The link between the Val/Val homozygosity and age over 50 years at diagnosis (OR 0.15, CI 95 % 0.02-1.2) was barely significant (p = 0.056). Summarizing, our data indicated a non-significant trend toward increased ovarian cancer risk in the Val/Val homozygosity, especially in women aged above 50 years. Further large-cohort studies focusing on the role of the HER2 codon 655 Val allele are needed.

HER2 Codon 655 (Ile/Val) Polymorphism and Breast Cancer in Austrian Women.

BACKGROUND: The overexpression of the human epidermal growth factor receptor 2 (HER2) in breast cancer (BC) is associated with impaired prognosis. Data concerning the HER2 codon 655 polymorphism (Ile/Val) and BC risk are conflicting. MATERIALS AND METHODS: We studied the HER2 codon 655 (rs1136201) polymorphism in 80 Austrian patients with BC and 100 healthy volunteers by pyrosequencing and polymerase chain reaction. Associations between codon 655 allelic variants and clinicopathological variables (e.g. age, stage of disease, tumor type, grading, and receptor status) were studied with 2×2 tables. RESULTS: The genotypic distributions in patients with BC (AA: 63.75%, AG: 32.5%, GG: 3.75%) and controls (AA: 63%, AG: 34%, GG: 3.7%) were virtually identical (odds ratio=1.03, 95% confidence interval=0.56-1.90). A non-significant link between carrying at least one G allele and more aggressive tumor type (estrogen receptor-negative p=0.08, G3 tumor p=0.19) was observed. CONCLUSION: Genotypic variation within the codon 655 of HER2 does not alter the BC risk in Caucasian Austrian women. The association between the G allele and more aggressive tumor types requires further investigation.

[Osteolysis of the hip joint in an eastern river cooter (Pseudemys concinna concinna)]. / Osteolyse des Hüftgelenks bei einer Hieroglyphen-Schmuckschildkröte (Pseudemys concinna concinna).

Lameness in freshwater turtles is rarely seen and is mostly caused by bite injuries, other traumata or inflammatory processes. A 17 year old female eastern river cooter which was pretreated for disseminated shell necrosis a few months ago was presented due to acute lameness of the right hind limb. Diagnostic imaging revealed complete lysis of the hip joint and was classified as necrotizing osteomyelitis by histopathology. Septicemic spreading of pathogens and thus a link to the previous shell necrosis could not be identified. The patient developed wound complications and died a few days after the surgical procedure. Postmortem, a pronounced subacute pneumonia was diagnosed as presumed cause of death, which has not been clinically manifest during the whole medical history.

HER2 Codon 655 (Ile/Val) Polymorphism and Breast Cancer in Austrian Women.

BACKGROUND: The overexpression of the human epidermal growth factor receptor 2 (HER2) in breast cancer (BC) is associated with impaired prognosis. Data concerning the HER2 codon 655 polymorphism (Ile/Val) and BC risk are conflicting. MATERIALS AND METHODS: We studied the HER2 codon 655 (rs1136201) polymorphism in 80 Austrian patients with BC and 100 healthy volunteers by pyrosequencing and polymerase chain reaction. Associations between codon 655 allelic variants and clinicopathological variables (e.g. age, stage of disease, tumor type, grading, and receptor status) were studied with 2×2 tables. RESULTS: The genotypic distributions in patients with BC (AA: 63.75%, AG: 32.5%, GG: 3.75%) and controls (AA: 63%, AG: 34%, GG: 3.7%) were virtually identical (odds ratio=1.03, 95% confidence interval=0.56-1.90). A non-significant link between carrying at least one G allele and more aggressive tumor type (estrogen receptor-negative p=0.08, G3 tumor p=0.19) was observed. CONCLUSION: Genotypic variation within the codon 655 of HER2 does not alter the BC risk in Caucasian Austrian women. The association between the G allele and more aggressive tumor types requires further investigation.

Measurement of intraocular pressure in healthy unanesthetized inland bearded dragons (Pogona vitticeps).

OBJECTIVE: To evaluate the use of rebound and applanation tonometry for the measurement of intraocular pressure (IOP) and to assess diurnal variations in and the effect of topical anesthesia on the IOP of healthy inland bearded dragons (Pogona vitticeps). ANIMALS: 56 bearded dragons from 4 months to 11 years old. PROCEDURES: For each animal following an initial ophthalmic examination, 3 IOP measurements were obtained on each eye between 9 AM and 10 AM, 1 PM and 2 PM, and 5 PM and 7 PM by use of rebound and applanation tonometry. An additional measurement was obtained by rebound tonometry for each eye in the evening following the application of a topical anesthetic to evaluate changes in the tolerance of the animals to the tonometer. Descriptive data were generated, and the effects of sex, time of day, and topical anesthesia on IOP were evaluated. RESULTS: Bearded dragons did not tolerate applanation tonometry even following topical anesthesia. Median daily IOP as determined by rebound tonometry was 6.16 mm Hg (95% confidence interval, 5.61 to 6.44 mm Hg). The IOP did not differ significantly between the right and left eyes. The IOP was highest in the morning, which indicated that the IOP in this species undergoes diurnal variations. Topical anesthesia did not significantly affect IOP, but it did improve the compliance for all subjects. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that rebound tonometry, but not applanation tonometry, was appropriate for measurement of IOP in bearded dragons. These findings provided preliminary guidelines for IOP measurement and ophthalmic evaluation in bearded dragons.

Consolidating the State of Knowledge: A Synoptical Review of Wind Energy's Wildlife Effects.

Wind energy development contributes substantially to achieve climate protection goals. Unintended side effects, especially on wildlife, have long been discussed and substantial research has evolved over the last decade. At this stage, it is important to identify what we have learnt so far, as well as which predominant uncertainties and gaps remain. This review article aims to consolidate the state of knowledge, providing a qualitative analysis of the main effects of wind energy development on- and offshore, focusing on frequently studied species groups (bats, breeding and resting birds, raptors, migratory birds, marine mammals). We reviewed over 220 publications from which we identified predominant hypotheses that were summarized and displayed in tables. Journal publications, conference contributions, and further studies have been considered. We found that research focusing on offshore wind energy within the last couple of years has increased significantly as well, catching up with the vast amount of onshore studies. Some hypotheses have been verified by numerous publications and a consensus has been reached (e.g., correlation between bat activity and weather factors), while others are still being debated more (e.g., determination of migratory corridors) or remain unknown (e.g., effect on population level). Factors influencing potential effects were mainly related to species characteristics (morphology, phenology, abundance, behavior, and response to turbines) or site characteristics (landscape features, weather, and habitat quality). Consolidating the state of research provides the groundwork for the identification of mitigation measures and advanced planning approaches. However, the quantification of effects remains challenging and uncertainties will always persist.

Cautious but committed: moving toward adaptive planning and operation strategies for renewable energy's wildlife implications.

Wildlife planning for renewable energy must cope with the uncertainties of potential wildlife impacts. Unfortunately, the environmental policies which instigate renewable energy and those which protect wildlife are not coherently aligned-creating a green versus green dilemma. Thus, climate mitigation efforts trigger renewable energy development, but then face substantial barriers from biodiversity protection instruments and practices. This article briefly reviews wind energy and wildlife interactions, highlighting the lively debated effects on bats. Today, planning and siting of renewable energy are guided by the precautionary principle in an attempt to carefully address wildlife challenges. However, this planning attitude creates limitations as it struggles to negotiate the aforementioned green versus green dilemma. More adaptive planning and management strategies and practices hold the potential to reconcile these discrepancies to some degree. This adaptive approach is discussed using facets of case studies from policy, planning, siting, and operational stages of wind energy in Germany and the United States, with one case showing adaptive planning in action for solar energy as well. This article attempts to highlight the benefits of more adaptive approaches as well as the possible shortcomings, such as reduced planning security for renewable energy developers. In conclusion, these studies show that adaptive planning and operation strategies can be designed to supplement and enhance the precautionary principle in wildlife planning for green energy.

Role of miR-34a as a suppressor of L1CAM in endometrial carcinoma.

L1CAM promotes cell motility, invasion and metastasis formation in various human cancers and can be considered as a driver of tumor progression. Knowledge about genetic processes leading to the presence of L1CAM in cancers is of considerable importance. Experimentally, L1CAM expression can be achieved by various means. Over-expression of the transcription factor SLUG or treatment of cells with TGF-ß1 can induce or augment L1CAM levels in cancer cells. Likewise, hypomethylation of the L1CAM promoter on the X chromosome correlates with L1CAM expression. However, presently no mechanisms that might control transcriptional activity are known. Here we have identified miR-34a as a suppressor of L1CAM. We observed that L1CAM positive endometrial carcinoma (EC) cell lines HEC1B and SPAC1L lost L1CAM protein and mRNA by treatment with demethylating agents or knock-down of the DNA-methyltransferase-1 (DNMT1). Concomitantly, several miRNAs were up-regulated. Using miRNA profiling, luciferase reporter assays and mutagenesis, we identified miR-34a as a putative binder to the L1CAM-3'UTR. Over-expression of miR-34a in HEC1B cells blocked L1CAM expression and inhibited cell migration. In ECC1 cells (wildtype p53) the activation of p53 caused miR-34a up-regulation and loss of L1CAM expression that was miR-34a dependent. We observed an inverse correlation between L1CAM and miR-34a levels in EC cell lines. In primary tumor sections areas expressing high amounts of L1CAM had less miR-34a expression than those with low L1CAM levels. Our data suggest that miR-34a can regulate L1CAM expression by targeting L1CAM mRNA for degradation. These findings shed new light on the complex regulation of L1CAM in human tumors.