Alternative promoters and splicing create multiple functionally distinct isoforms of oestrogen receptor alpha in breast cancer and healthy tissues.

BACKGROUND: Oestrogen receptor alpha (ER) is involved in cell growth and proliferation and functions as a transcription factor, a transcriptional coregulator, and in cytoplasmic signalling. It affects, for example, bone, endometrium, ovaries and mammary epithelium. It is a key biomarker in clinical management of breast cancer, where it is used as a prognostic and treatment-predictive factor, and a therapeutical target. Several ER isoforms have been described, but transcript annotation in public databases is incomplete and inconsistent, and functional differences are not well understood. METHODS: We have analysed short- and long-read RNA sequencing data from breast tumours, breast cancer cell lines, and normal tissues to create a comprehensive annotation of ER transcripts and combined it with experimental studies of full-length protein and six alternative isoforms. RESULTS: The isoforms have varying transcription factor activity, subcellular localisation, and response to the ER-targeting drugs tamoxifen and fulvestrant. Antibodies differ in ability to detect alternative isoforms, which raises concerns for the interpretation of ER-status in routine pathology. CONCLUSIONS: Future work should investigate the effects of alternative isoforms on patient survival and therapy response. An accurate annotation of ER isoforms will aid in interpretation of clinical data and inform functional studies to improve our understanding of the ER in health and disease.

Efficacy of Chest CT for COVID-19 Pneumonia Diagnosis in France.

Background The role and performance of chest CT in the diagnosis of the coronavirus disease 2019 (COVID-19) pandemic remains under active investigation. Purpose To evaluate the French national experience using chest CT for COVID-19, results of chest CT and reverse transcription polymerase chain reaction (RT-PCR) assays were compared together and with the final discharge diagnosis used as the reference standard. Materials and Methods A structured CT scan survey (NCT04339686) was sent to 26 hospital radiology departments in France between March 2, 2020, and April 24, 2020. These dates correspond to the peak of the national COVID-19 epidemic. Radiology departments were selected to reflect the estimated geographic prevalence heterogeneities of the epidemic. All symptomatic patients suspected of having COVID-19 pneumonia who underwent both initial chest CT and at least one RT-PCR test within 48 hours were included. The final discharge diagnosis, based on multiparametric items, was recorded. Data for each center were prospectively collected and gathered each week. Test efficacy was determined by using the Mann-Whitney test, Student t test, χ2 test, and Pearson correlation coefficient. P < .05 indicated a significant difference. Results Twenty-six of 26 hospital radiology departments responded to the survey, with 7500 patients entered; 2652 did not have RT-PCR test results or had unknown or excess delay between the RT-PCR test and CT. After exclusions, 4824 patients (mean age, 64 years ± 19 [standard deviation], 2669 male) were included. With final diagnosis as the reference, 2564 of the 4824 patients had COVID-19 (53%). Sensitivity, specificity, negative predictive value, and positive predictive value of chest CT in the diagnosis of COVID-19 were 2319 of 2564 (90%; 95% CI: 89, 91), 2056 of 2260 (91%; 95% CI: 91, 92), 2056 of 2300 (89%; 95% CI: 87, 90), and 2319 of 2524 (92%; 95% CI: 91, 93), respectively. There was no significant difference for chest CT efficacy among the 26 geographically separate sites, each with varying amounts of disease prevalence. Conclusion Use of chest CT for the initial diagnosis and triage of patients suspected of having coronavirus disease 2019 was successful. © RSNA, 2021 Online supplemental material is available for this article.

COVID-19 impact assessment on the French radiological centers: a nationwide survey.

PURPOSE: To determine the impact of the COVID-19 on the CT activities in French radiological centers during the epidemic peak. MATERIALS AND METHODS: A cross-sectional prospective CT scan survey was conducted between March 16 and April 12, 2020, in accordance with the local IRB. Seven hundred nine radiology centers were invited to participate in a weekly online survey. Numbers of CT examinations related to COVID-19 including at least chest (CTcovid) and whole chest CT scan activities (CTchest) were recorded each week. A sub-analysis on French departments was performed during the 4 weeks of the study. The impact of the number of RT-PCRs (reverse transcriptase polymerase chain reactions) on the CT workflow was tested using two-sample t test and Pearson's test. RESULTS: Five hundred seventy-seven structures finally registered (78%) with mean response numbers of 336 ± 18.9 (323; 351). Mean CTchest activity per radiologic structure ranged from 75.8 ± 133 (0-1444) on week 12 to 99.3 ± 138.6 (0-1147) on week 13. Mean ratio of CTcovid on CTchest varied from 0.36 to 0.59 on week 12 and week 14 respectively. There was a significant relationship between the number of RT-PCR performed and the number of CTcovid (r = 0.73, p = 3.10-16) but no link with the number of positive RT-PCR results. CONCLUSION: In case of local high density COVID-19, CT workflow is strongly modified and redirected to the management of these specific patients. KEY POINTS: • Over the 4-week survey period, 117,686 chest CT (CTtotal) were performed among the responding centers, including 61,784 (52%) CT performed for COVID-19 (CTcovid). • Across the country, the ratio CTcovid/CTtotal varied from 0.36 to 0.59 and depended significantly on the local epidemic density (p = 0.003). • In clinical practice, in a context of growing epidemic, in France, chest CT was used as a surrogate to RT-PCR for patient triage.

Occurrence of Incomplete Endothelialization Causing Residual Permeability After Left Atrial Appendage Closure.

AIMS: Percutaneous left atrial appendage (LAA) occlusion is occasionally incomplete, with residual permeability of the LAA on cardiac computed tomography. The cause for this is unclear. Our objective was to determine if residual permeability was related to incomplete endothelialization. METHODS: A total of 35 consecutive patients contraindicated for anticoagulant therapy admitted for LAA occlusion were included; 12 patients received a Watchman device (Boston Scientific) and 23 patients received an Amplatzer Cardiac Plug (St. Jude Medical). Incomplete endothelialization was defined as residual permeability on cardiac computed tomography without peridevice leak on transesophageal echocardiography at follow-up. RESULTS: Five patients did not receive cardiac computed tomography. After 10 ± 6 months of follow-up, residual permeability of the LAA (at least partial) was recorded on cardiac computed tomography in 21 of 30 patients (70%). Seven of 30 patients presented with a peridevice leak on transesophageal echocardiography. Among the remaining 23 patients, 14 (61%) presented with incomplete endothelialization and 9 (39%) presented with complete endothelialization. There was no statistical difference between the patients presenting with complete vs incomplete endothelialization. CONCLUSION: We found that incomplete endothelialization, defined as residual permeability on cardiac computed tomography without peridevice leak on transesophageal echocardiography, occurred in 61% of the patients after 10 ± 6 months of percutaneous LAA closure. Predisposing factors and appropriate monitoring of LAA patients remain to be determined in larger cohorts.

Volatile organic compounds (VOCs) in exhaled breath of patients with breast cancer in a clinical setting.

BACKGROUND: Carcinogenic products in the exhaled breath of cancer patients are of growing medical interest as they can serve as noninvasive disease markers. Breath analysis can be used as an alternative or complementary diagnostic tool in breast cancer patients who have a different pattern of chemical composition in their breath. This study aims to verify the existence of specific volatile organic compounds (VOCs) in the breath of breast cancer patients. METHODS: This prospective study included ten patients suffering from breast cancer and ten healthy pair-matched women. Breath samples of each member of the two respective groups were taken and scanned by gas chromatography/mass spectometry for the presence of volatile organic compounds such as alkanes, ketones, halogenated hydrocarbon, aldehydes, and esters. RESULTS: The spectrum of VOCs differed significantly within the two groups. Five specific VOCs could be identified as typical discriminatory markers in the breath samples. Four VOCs were elevated in the healthy controls, one specific VOC was found to be elevated in women affected by breast cancer CONCLUSIONS: This pilot study revealed a specific VOC pattern using gas chromatography in the breath of breast cancer patients. Five specific breast cancer-VOCs were identified. At relatively low cost the identification of VOCs may be used to detect breast cancer.

Expression and localization of e-cadherin in epithelial ovarian cancer.

BACKGROUND: Findings for the role of E-cadherin in ovarian cancer (OC) are controversial. The aim of this study was to analyze the expression and prognostic role of E-cadherin in OC. MATERIALS AND METHODS: Expression analysis of E-cadherin was performed by immunohistochemistry in 36 patients (12 primary OC, 15 recurrent OC, 9 benign ovarian lesions). Tumor specimens were collected within OC. Correlation analysis with clinicopathological factors and survival was performed. RESULTS: E-Cadherin was significantly reduced in OC compared to benign ovarian lesions (p=0.024). In primary OC, E-cadherin was comparable in ovarian tumor and corresponding metastatic tumor tissue. E-Cadherin showed no association with clinicopathological factors. A significant correlation between increased volume of ascites and higher E-cadherin immunoexpression was found in primary OC (p=0.029). E-Cadherin expression showed no statistically prognostic significance for survival (p=0.856). CONCLUSION: The function of E-cadherin in OC remains controversial and needs to be elucidated further in larger studies.