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PURPOSE: Endometrioid ovarian carcinoma (ENOC) is the second most-common type of ovarian carcinoma, comprising 10%-20% of cases. Recently, the study of ENOC has benefitted from comparisons to endometrial carcinomas including defining ENOC with four prognostic molecular subtypes. Each subtype suggests differential mechanisms of progression, although tumor-initiating events remain elusive. There is evidence that the ovarian microenvironment may be critical to early lesion establishment and progression. However, while immune infiltrates have been well studied in high-grade serous ovarian carcinoma, studies in ENOC are limited. EXPERIMENTAL DESIGN: We report on 210 ENOC, with clinical follow-up and molecular subtype annotation. Using multiplex IHC and immunofluorescence, we examine the prevalence of T-cell lineage, B-cell lineage, macrophages, and populations with programmed cell death protein 1 or programmed death-ligand 1 across subtypes of ENOC. RESULTS: Immune cell infiltrates in tumor epithelium and stroma showed higher densities in ENOC subtypes with known high mutation burden (POLEmut and MMRd). While molecular subtypes were prognostically significant, immune infiltrates were not (overall survival P > 0.2). Analysis by molecular subtype revealed that immune cell density was prognostically significant in only the no specific molecular profile (NSMP) subtype, where immune infiltrates lacking B cells (TILB minus) had inferior outcome (disease-specific survival: HR, 4.0; 95% confidence interval, 1.1-14.7; P < 0.05). Similar to endometrial carcinomas, molecular subtype stratification was generally superior to immune response in predicting outcomes. CONCLUSIONS: Subtype stratification is critical for better understanding of ENOC, in particular the distribution and prognostic significance of immune cell infiltrates. The role of B cells in the immune response within NSMP tumors warrants further study.

Abstract Malignant melanoma, the most aggressive form of skin cancer, is often incurable once metastatic dissemination of cancer cells to distant organs has occurred. We investigated the role of Transcription Factor Activating Enhancer-Binding Protein 2ε (AP2ε) in the progression of metastatic melanoma. Here, we observed that AP2ε is a potent activator of metastasis and newly revealed AP2ε to be an important player in melanoma plasticity. High levels of AP2ε lead to worsened prognosis of melanoma patients. Using a transgenic melanoma mouse model with a specific loss of AP2ε expression, we confirmed the impact of AP2ε to modulate the dynamic switch from a migratory to a proliferative phenotype. AP2ε deficient melanoma cells show a severely reduced migratory potential in vitro and reduced metastatic behavior in vivo. Consistently, we revealed increased activity of AP2ε in quiescent and migratory cells compared to heterogeneously proliferating cells in bioprinted 3D models. In conclusion, these findings disclose a yet-unknown role of AP2ε in maintaining plasticity and migration in malignant melanoma cells.

Abstract Background The German Rivermead Post-Concussion Symptoms Questionnaire (RPQ) can be used to assess post-concussion symptoms (PCS) after traumatic brain injury (TBI) in adults, adolescents, and children. Methods In this study, we examined the psychometric properties of the German RPQ proxy version (N = 146) for children (8—12 years) after TBI at the item, total and scale score level. Construct validity was analyzed using rank correlations with the proxy-assessed Post-Concussion Symptoms Inventory (PCSI-P), the Patient Health Questionnaire 9 (PHQ-9), and the Generalized Anxiety Disorder Scale 7 (GAD-7). Furthermore, sensitivity testing was performed concerning subjects’ sociodemographic and injury-related characteristics. Differential item functioning (DIF) was analyzed to assess the comparability of RPQ proxy ratings for children with those for adolescents. Results Good internal consistency was demonstrated regarding Cronbach’s α (0.81—0.90) and McDonald’s ω (0.84—0.92). The factorial validity of a three-factor model was superior to the original one-factor model. Proxy ratings of the RPQ total and scale scores were strongly correlated with the PCSI-P (ϱ = 0.50—0.69), as well as moderately to strongly correlated with the PHQ-9 (ϱ = 0.49—0.65) and the GAD-7 (ϱ = 0.44—0.64). The DIF analysis revealed no relevant differences between the child and adolescent proxy versions. Conclusions The German RPQ proxy is a psychometrically reliable and valid instrument for assessing PCS in children after TBI. Therefore, RPQ self- and proxy-ratings can be used to assess PCS in childhood as well as along the lifespan of an individual after TBI.

Abstract Malignant melanoma remains the most lethal form of skin cancer, exhibiting poor prognosis after forming distant metastasis. Owing to their potential tumor-suppressive properties by regulating oncogenes and tumor suppressor genes, microRNAs are important player in melanoma development and progression. We defined the loss of miR-101-3p expression in melanoma cells compared with melanocytes and melanoblast-related cells as an early event in tumor development and aimed to understand the tumor suppressive role of miR-101-3p and its regulation of important cellular processes. Reexpression of miR-101-3p resulted in inhibition of proliferation, increase in DNA damage, and induction of apoptosis. We further determined the nuclear structure protein Lamin B1, which influences nuclear processes and heterochromatin structure, ATRX, CASP3, and PARP as an important direct target of miR-101-3p. RNA sequencing and differential gene expression analysis after miR-101-3p reexpression supported our findings and the importance of loss of mir-101-3p for melanoma progression. The validated functional effects are related to genomic instability, as recent studies suggest miRNAs plays a key role in mediating this cellular process. Therefore, we concluded that miR-101-3p reexpression increases the genomic instability, leading to irreversible DNA damage, which leads to apoptosis induction. Our findings suggest that the loss of miR-101-3p in melanoma serves as an early event in melanoma progression by influencing the genomic integrity to maintain the increased bioenergetic demand.

The identification and reduction of methane sources is considered an important part of the fight to stem greenhouse gas (GHG) emissions to the atmosphere. One of the largest industrial contributors to national GHG emissions in Canada is the Alberta Oil Sands Region. To quantify and investigate the spatial distribution and temporal variability of methane emissions from this region, airborne measurements were conducted in 2017 and 2018 with three aircraft. 59 flights were conducted in total to assess emissions for both open-pit and in-situ facilities, in both cold and warm seasons. Derived emission rates were higher than those reported in national inventories by 30%–96% depending on the facility. In-situ facilities had emission rates an order of magnitude lower than surface mining operations and differed significantly from inventory estimates. No statistical differences in CH4 emissions between cold and warm seasons were observed, substantiating the use of simple upscaling to annual emissions within inventories. Rather than confirming a reported decrease in emissions between 2013 and 2018, the measurements suggest essentially no change from the 18 t h−1 for the region observed in 2013. Overall, the results suggest that current methods of CH4 emission determination within the oil sands region, for use in reporting, require improvement.

BackgroundRecently, we showed a >60% difference in 5-year survival for patients with tubo-ovarian high-grade serous carcinoma (HGSC) when stratified by a 101-gene mRNA expression prognostic signature. Given the varied patient outcomes, this study aimed to translate prognostic mRNA markers into protein expression assays by immunohistochemistry and validate their survival association in HGSC.MethodsTwo prognostic genes, FOXJ1 and GMNN, were selected based on high-quality antibodies, correlation with protein expression and variation in immunohistochemical scores in a preliminary cohort (n = 134 and n = 80, respectively). Six thousand four hundred and thirty-four (FOXJ1) and 5470 (GMNN) formalin-fixed, paraffin-embedded ovarian neoplasms (4634 and 4185 HGSC, respectively) represented on tissue microarrays from the Ovarian Tumor Tissue Analysis consortium underwent immunohistochemical staining and scoring, then univariate and multivariate survival analysis.ResultsConsistent with mRNA, FOXJ1 protein expression exhibited a linear, increasing association with improved overall survival in HGSC patients. Women with >50% expression had the most favourable outcomes (HR = 0.78, 95% CI 0.67-0.91, p 35% GMNN expression showed a trend for better outcomes, though this was not significant.ConclusionWe provide foundational evidence for the prognostic value of FOXJ1 in HGSC, validating the prior mRNA-based prognostic association by immunohistochemistry.

A primary sink of air pollutants and their precursors is dry deposition. Dry deposition estimates differ across chemical transport models, yet an understanding of the model spread is incomplete. Here, we introduce Activity 2 of the Air Quality Model Evaluation International Initiative Phase 4 (AQMEII4). We examine 18 dry deposition schemes from regional and global chemical transport models as well as standalone models used for impact assessments or process understanding. We configure the schemes as single-point models at eight Northern Hemisphere locations with observed ozone fluxes. Single-point models are driven by a common set of site-specific meteorological and environmental conditions. Five of eight sites have at least 3 years and up to 12 years of ozone fluxes. The interquartile range across models in multiyear mean ozone deposition velocities ranges from a factor of 1.2 to 1.9 annually across sites and tends to be highest during winter compared with summer. No model is within 50 % of observed multiyear averages across all sites and seasons, but some models perform well for some sites and seasons. For the first time, we demonstrate how contributions from depositional pathways vary across models. Models can disagree with respect to relative contributions from the pathways, even when they predict similar deposition velocities, or agree with respect to the relative contributions but predict different deposition velocities. Both stomatal and nonstomatal uptake contribute to the large model spread across sites. Our findings are the beginning of results from AQMEII4 Activity 2, which brings scientists who model air quality and dry deposition together with scientists who measure ozone fluxes to evaluate and improve dry deposition schemes in the chemical transport models used for research, planning, and regulatory purposes.

Background: Until now, limited clinical significance had been reported for disseminated tumor cells (DTCs) in gynecologic malignancies. DTCs were previously reported not to be associated with established risk factors, L1CAM immunoreactivity, and outcome in endometrial carcinoma (EC). This study’s primary objective was to investigate potential correlations of DTCs in the bone marrow (BM) of EC patients with disease-related survival, and a secondary objective was to evaluate associations between molecular classification of EC and DTCs. Methods: Patients treated for primary EC at Tuebingen University women’s hospital between 2003 and 2016 were identified. A total of 402 patients with a complete set of BM cytology, molecular, and clinical data were evaluable. Results: DTC occurrence was distributed equally among all four molecular groups (p = 0.651). DTC positivity was associated with a less favorable disease-free survival (HR: 1.86, 95% CI: 1.03–3.36, p = 0.036) and progression-free survival (HR: 1.86, 95% CI: 1.01–3.44, p = 0.045). Presence of DTCs was associated with a higher frequency of distant disease recurrence (p = 0.017). Conclusions: In line with our previous findings, tumor cell dissemination is not associated with molecular features in our large cohort of primary EC patients. Since DTCs seem to be associated with survival and location of disease recurrence, further studies are needed to decisively define their role in EC survival.

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p

Abstract Background Breast cancer is a metabolically heterogeneous disease, and although the concept of heterogeneous cancer metabolism is known, its precise role in human breast cancer is yet to be fully elucidated. Methods We investigated in an explorative approach a cohort of 42 primary mamma carcinoma patients with positron emission tomography/magnetic resonance imaging (PET/MR) prior to surgery, followed by histopathology and molecular diagnosis. From a subset of patients, which showed high metabolic heterogeneity based on tracer uptake and pathology classification, tumour centre and periphery specimen tissue samples were further investigated by a targeted breast cancer gene expression panel and quantitative metabolomics by nuclear magnetic resonance (NMR) spectroscopy. All data were analysed in a combinatory approach. Results [18F]FDG (2‐deoxy‐2‐[fluorine‐18]fluoro‐d‐glucose) tracer uptake confirmed dominance of glucose metabolism in the breast tumour centre, with lower levels in the periphery. Additionally, we observed differences in lipid and proliferation related genes between luminal A and B subtypes in the centre and periphery. Tumour periphery showed elevated acetate levels and enrichment in lipid metabolic pathways genes especially in luminal B. Furthermore, serine was increased in the periphery and higher expression of thymidylate synthase (TYMS) indicated one‐carbon metabolism increased in tumour periphery. The overall metabolic activity based on [18F]FDG uptake of luminal B subtype was higher than that of luminal A and the difference between the periphery and centre increased with tumour grade. Conclusion Our analysis indicates variations in metabolism among different breast cancer subtypes and sampling locations which details the heterogeneity of the breast tumours. Correlation analysis of [18F]FDG tracer uptake, transcriptome and tumour metabolites like acetate and serine facilitate the search for new candidates for metabolic tracers and permit distinguishing luminal A and B. This knowledge may help to differentiate subtypes preclinically or to provide patients guide for neoadjuvant therapy and optimised surgical protocols based on individual tumour metabolism.

Abstract Despite tremendous progress in deciphering breast cancer at the genomic level, the pronounced intra- and intertumoral heterogeneity remains a major obstacle to the advancement of novel and more effective treatment approaches. Frequent treatment failure and the development of treatment resistance highlight the need for patient-derived tumor models that reflect the individual tumors of breast cancer patients and allow a comprehensive analyses and parallel functional validation of individualized and therapeutically targetable vulnerabilities in protein signal transduction pathways. Here, we introduce the generation and application of breast cancer patient-derived 3D microtumors (BC-PDMs). Residual fresh tumor tissue specimens were collected from n = 102 patients diagnosed with breast cancer and subjected to BC-PDM isolation. BC-PDMs retained histopathological characteristics, and extracellular matrix (ECM) components together with key protein signaling pathway signatures of the corresponding primary tumor tissue. Accordingly, BC-PDMs reflect the inter- and intratumoral heterogeneity of breast cancer and its key signal transduction properties. DigiWest®-based protein expression profiling of identified treatment responder and non-responder BC-PDMs enabled the identification of potential resistance and sensitivity markers of individual drug treatments, including markers previously associated with treatment response and yet undescribed proteins. The combination of individualized drug testing with comprehensive protein profiling analyses of BC-PDMs may provide a valuable complement for personalized treatment stratification and response prediction for breast cancer.

The emission of SO2 from the Athabasca Oil Sands Region (AOSR) has been shown to impact the surrounding forest area. Recent studies using aircraft-based measurements have demonstrated that deposition of SO2 to the forest is at a rate many times higher than model estimates. Here we use the flux–gradient method to estimate SO2 deposition rates at two tower sites in the boreal forest downwind of AOSR SO2 emissions. We use both continuous and passive sampler measurements and compare the two techniques. The measurements infer SO2 deposition velocities ranging from 2.1–5.9 cm s−1 (when corrections are applied). There are uncertainties associated with the passive sampler flux–gradient analysis, primarily due to an assumed Schmidt number, a required assumption of independent variables, and potential wind effects. We estimate the total uncertainty as ± 2 cm s−1. Accounting for these uncertainties, the range of measurements is approximately double the previous aircraft-based measurements (1.2–3.4 cm s−1) and more than 10 times higher than model estimates for the same measurement periods (0.1–0.6 cm s−1), suggesting that SO2 in the AOSR has a much shorter lifetime in the atmosphere than is currently predicted by models.

Targeted therapies with chemotherapeutic agents and immunotherapy with checkpoint inhibitors are among the systemic therapies recommended in the guidelines for clinicians to treat melanoma. Although there have been constant improvements in the treatment of melanoma, resistance to the established therapies continues to occur. Therefore, the purpose of this study was to explore the function of garcinol with regards to specific cancer properties such as proliferation and apoptosis. Garcinol, a natural compound isolated from the plant also known as mangosteen (Garcinia mangostana), is a newly discovered option for cancer treatment. Numerous pharmaceutical substances are derived from plants. For example, the derivates of camptothecin, extracted from the bark of the Chinese tree of happiness (Camptotheca acuminate), or paclitaxel, extracted from the bark of the Western yew tree (Taxus brevifolia), are used as anti-cancer drugs. Here, we show that garcinol reduced proliferation and induced apoptosis in melanoma cell lines. In addition, we found that those cells that are positive for the expression of the cell–cell adhesion molecule T-cadherin (CDH13) respond more sensitively to treatment with garcinol. After knock-down experiments with an siRNA pool against T-cadherin, the sensitivity to garcinol decreased and proliferation and anti-apoptotic behavior of the cells was restored. We conclude that patients who are T-cadherin-positive could especially benefit from a therapy with garcinol.

Nuclear factor of activated T cells 5 (NFAT5) and cyclooxygenase 2 (COX2; PTGS2) both participate in diverse pathologies including cancer progression. However, the biological role of the NFAT5-COX2 signaling pathway in human endometrial cancer has remained elusive. The present study explored whether NFAT5 is expressed in endometrial tumors and if NFAT5 participates in cancer progression. To gain insights into the underlying mechanisms, NFAT5 protein abundance in endometrial cancer tissue was visualized by immunohistochemistry and endometrial cancer cells (Ishikawa and HEC1a) were transfected with NFAT5 or with an empty plasmid. As a result, NFAT5 expression is more abundant in high-grade than in low-grade endometrial cancer tissue. RNA sequencing analysis of NFAT5 overexpression in Ishikawa cells upregulated 37 genes and downregulated 20 genes. Genes affected included cyclooxygenase 2 and hypoxia inducible factor 1α (HIF1A). NFAT5 transfection and/or treatment with HIF-1α stabilizer exerted a strong stimulating effect on HIF-1α promoter activity as well as COX2 expression level and prostaglandin E2 receptor (PGE2) levels. Our findings suggest that activation of NFAT5—HIF-1α—COX2 axis could promote endometrial cancer progression.

Abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

Measurements of size-resolved aerosol concentration and fluxes were made in a forest in the Athabasca Oil Sands Region (AOSR) of Alberta, Canada, in August 2021 with the aim of investigating (a) particle size distributions from different sources, (b) size-resolved particle deposition velocities, and (c) the rate of vertical mixing in the canopy. Particle size distributions were attributed to different sources determined by wind direction. Air mixed with smokestack plumes from oil sands processing facilities had higher number concentrations with peak number at diameters near 70 nm. Aerosols from the direction of open-pit mine faces showed number concentration peaks near 150 nm and volume distribution peaks near 250 nm (with secondary peaks near 600 nm). Size-resolved deposition fluxes were calculated which show good agreement with previous measurements and a recent parameterization. There is a minimum deposition velocity of vd=0.02 cm s−1 for particles of 80 nm diameter; however, there is a large amount of variation in the measurements, and this value is not significantly different from zero in the 68 % confidence interval. Finally, gradient measurements of aerosol particles (with diameters <1 µm) demonstrated nighttime decoupling of air within and above the forest canopy, with median lag times at night of up to 40 min and lag times between 2 and 5 min during the day. Aerosol mass fluxes (diameters <1 µm) determined using flux–gradient methods (with different diffusion parameterizations) underestimate the flux magnitude relative to eddy covariance flux measurements when averaged over the nearly 1-month measurement period. However, there is significant uncertainty in the averages determined using the flux–gradient method.

Large datasets of greenhouse gas and energy surface-atmosphere fluxes measured with the eddy-covariance technique (e.g., FLUXNET2015, AmeriFlux BASE) are widely used to benchmark models and remote-sensing products. This study addresses one of the major challenges facing model-data integration: To what spatial extent do flux measurements taken at individual eddy-covariance sites reflect model- or satellite-based grid cells? We evaluate flux footprints—the temporally dynamic source areas that contribute to measured fluxes—and the representativeness of these footprints for target areas (e.g., within 250–3000 m radii around flux towers) that are often used in flux-data synthesis and modeling studies. We examine the land-cover composition and vegetation characteristics, represented here by the Enhanced Vegetation Index (EVI), in the flux footprints and target areas across 214 AmeriFlux sites, and evaluate potential biases as a consequence of the footprint-to-target-area mismatch. Monthly 80% footprint climatologies vary across sites and through time ranging four orders of magnitude from 103 to 107 m2 due to the measurement heights, underlying vegetation- and ground-surface characteristics, wind directions, and turbulent state of the atmosphere. Few eddy-covariance sites are located in a truly homogeneous landscape. Thus, the common model-data integration approaches that use a fixed-extent target area across sites introduce biases on the order of 4%–20% for EVI and 6%–20% for the dominant land cover percentage. These biases are site-specific functions of measurement heights, target area extents, and land-surface characteristics. We advocate that flux datasets need to be used with footprint awareness, especially in research and applications that benchmark against models and data products with explicit spatial information. We propose a simple representativeness index based on our evaluations that can be used as a guide to identify site-periods suitable for specific applications and to provide general guidance for data use.

Large datasets of greenhouse gas and energy surface-atmosphere fluxes measured with the eddy-covariance technique (e.g., FLUXNET2015, AmeriFlux BASE) are widely used to benchmark models and remote-sensing products. This study addresses one of the major challenges facing model-data integration: To what spatial extent do flux measurements taken at individual eddy-covariance sites reflect model- or satellite-based grid cells? We evaluate flux footprints—the temporally dynamic source areas that contribute to measured fluxes—and the representativeness of these footprints for target areas (e.g., within 250–3000 m radii around flux towers) that are often used in flux-data synthesis and modeling studies. We examine the land-cover composition and vegetation characteristics, represented here by the Enhanced Vegetation Index (EVI), in the flux footprints and target areas across 214 AmeriFlux sites, and evaluate potential biases as a consequence of the footprint-to-target-area mismatch. Monthly 80% footprint climatologies vary across sites and through time ranging four orders of magnitude from 103 to 107 m2 due to the measurement heights, underlying vegetation- and ground-surface characteristics, wind directions, and turbulent state of the atmosphere. Few eddy-covariance sites are located in a truly homogeneous landscape. Thus, the common model-data integration approaches that use a fixed-extent target area across sites introduce biases on the order of 4%–20% for EVI and 6%–20% for the dominant land cover percentage. These biases are site-specific functions of measurement heights, target area extents, and land-surface characteristics. We advocate that flux datasets need to be used with footprint awareness, especially in research and applications that benchmark against models and data products with explicit spatial information. We propose a simple representativeness index based on our evaluations that can be used as a guide to identify site-periods suitable for specific applications and to provide general guidance for data use.

Abstract Background The SRY-related HMG-box family of transcription factors member SOX2 has been mainly studied in embryonic stem cells as well as early foregut and neural development. More recently, SOX2 was shown to participate in reprogramming of adult somatic cells to a pluripotent stem cell state and implicated in tumorigenesis in various organs. In breast cancer, SOX2 expression was reported as a feature of basal-like tumors. In this study, we assessed SOX2 expression in 95 primary tumors of postmenopausal breast cancer patients. Methods Samples from 95 patients diagnosed and treated at the University of Tuebingen Institute of Pathology and Women's Hospital were analyzed by immunohistochemistry for SOX2 expression in the primary tumor samples and in corresponding lymph node metastasis, where present. Furthermore, SOX2 amplification status was assessed by FISH in representative samples. In addition, eighteen fresh frozen samples were analyzed for SOX2, NANOG and OCT4 gene expression by real-time PCR. Results SOX2 expression was detected in 28% of invasive breast carcinoma as well as in 44% of ductal carcinoma in situ (DCIS) lesions. A score of SOX2 expression (score 0 to 3) was defined in order to distinguish SOX2 negative (score 0) from SOX2 positive samples (score 1-3) and among latter the subgroup of SOX2 high expressors (score 3 > 50% positive cells). Overall, the incidence of SOX2 expression (score 1-3) was higher than previously reported in a cohort of lymph node negative patients (28% versus 16.7%). SOX2 expression was detected across different breast cancer subtypes and did not correlate with tumor grading. However, high SOX2 expression (score 3) was associated with larger tumor size (p = 0.047) and positive lymph node status (0.018). Corresponding metastatic lymph nodes showed higher SOX2 expression and were significantly more often SOX2 positive than primary tumors (p = 0.0432). Conclusions In this report, we show that the embryonic stem cell factor SOX2 is expressed in a variety of early stage postmenopausal breast carcinomas and metastatic lymph nodes. Our data suggest that SOX2 plays an early role in breast carcinogenesis and high expression may promote metastatic potential. Further studies are needed to explore whether SOX2 can predict metastatic potential at an early tumor stage.