Effectiveness and safety of the radiofrequency ablation of single hyperfunctioning parathyroid lesions suggestive of adenomas in primary hyperparathyroidism.

INTRODUCTION: Radiofrequency ablation (RFA) has emerged as a minimally invasive approach to single parathyroid adenoma in primary hyperparathyroidism; however, there is limited evidence on its effectiveness. OBJECTIVE: To evaluate the effectiveness and safety of RFA to treat hyper-functioning parathyroid lesions suggestive of adenomas. MATERIAL AND METHODS: A prospective study was conducted in consecutive patients with primary hyperparathyroidism treated with RFA for single parathyroid lesions in our reference center between November 2017 and June 2021. Pre-treatment (baseline) and follow-up analytical data were gathered on total protein-adjusted calcium, parathyroid hormone [PTH], phosphorus, and 24-h urine calcium. Effectiveness was defined as complete response (normal calcium and PTH), partial response (reduced but not normalized PTH with normal serum calcium), or disease persistence (elevated calcium and PTH). SPSS 15.0 was used for statistical analysis. RESULTS: Four of thirty-three enrolled patients were lost to the follow-up. The final sample comprised 29 patients (22 females) with mean age of 60.93 ± 13.28 years followed up for a mean of 16.29 ± 7.23 months. Complete response was observed in 48.27%, partial response in 37.93%, and hyperparathyroidism persistence in 13.79%. Serum calcium and PTH levels were significantly lower at 1 and 2 years of post-treatment than at baseline. Adverse effects were mild, with two cases of dysphonia (self-limited in one patient) and no cases of hypocalcaemia or hypoparathyroidism. CONCLUSION: RFA may be a safe and effective technique to treat hyper-functioning parathyroid lesions in selected patients.

Radiofrequency ablation for thyroid and parathyroid disease.

Radiofrequency ablation is a well-known, safe, and effective method for treating benign thyroid nodules and recurring thyroid cancer as well as parathyroid adenomas that has yielded promising results in recent years. Since the Korean Society of Thyroid Radiology introduced the devices and the basic techniques for radiofrequency ablation in 2012, radiofrequency ablation has been approved all over the world and both the devices and techniques have improved. This review aims to instruct interventional radiologists who are doing or intend to start doing radiofrequency ablation of thyroid and parathyroid lesions, as well as thyroid and parathyroid specialists who provide pre- and post-operative care, in the training, execution, and quality control for radiofrequency ablation of thyroid nodules and parathyroid adenomas to optimize the efficacy and safety of the treatment.

Radiology volunteers to support a breast cancer screening program in Peru: Description of the project, preliminary results, and impressions.

Breast cancer is the second most common cancer in Peruvian women. Due to limitations in national breast cancer screening programs, especially in rural areas, more than 50% of cases of breast cancer in Peru are diagnosed in advanced stages. In collaboration with a local clinic registered as a nongovernmental organization (CerviCusco), RAD-AID International aims to create a sustainable diagnostic structure to improve breast cancer screening in Cuzco. With the support of local, national, and international partners that have collaborated in analyzing radiological resources, raising awareness in the population, acquiring equipment, training clinical staff, and building referral networks, our teams of radiologists, included in the RAD-AID team, have participated in training CerviCusco staff in breast ultrasound, thus enabling additional training for radiology residents through a regulated international collaboration.

Comprehensive assessment of germline pathogenic variant detection in tumor-only sequencing.

BACKGROUND: Tumor-only sequencing, implemented for the identification of somatic variants, is oftentimes used for the detection of actionable germline variants. We sought to determine whether tumor-only sequencing assays are suitable for detection of actionable germline variants, given their importance for the delivery of targeted therapies and risk-reducing measures. PATIENTS AND METHODS: The detection of germline variants affecting moderate- and high-penetrance cancer susceptibility genes (CSGs) by tumor-only sequencing was compared to clinical germline testing in 21 333 cancer patients who underwent tumor and germline testing using the Food and Drug Administration (FDA)-authorized Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Targets (MSK-IMPACT) assay. Seven homologous recombination deficiency (HRD), two DNA damage response (DDR) and four mismatch repair (MMR) genes, as well as NF1, RB1 and TP53 were included in the analysis. FDA-authorized and New York State Department of Health-approved sequencing methods for germline, tumor/normal and tumor-only sequencing assays and analytical pipelines were employed. RESULTS: In patients who underwent tumor and germline sequencing, as compared to clinical genetic testing, tumor-only sequencing failed to detect 10.5% of clinically actionable pathogenic germline variants in CSGs, including 18.8%, 12.8% and 7.3% of germline variants in MMR, DDR and HRD genes, respectively. The sensitivity for detection of pathogenic germline variants by tumor-only sequencing was 89.5%. Whilst the vast majority of pathogenic germline exonic single-nucleotide variants (SNVs) and small indels were detected by tumor-only sequencing, large percentages of germline copy number variants, intronic variants and repetitive element insertions were not detected. CONCLUSIONS: Tumor-only sequencing is adequate for the detection of clinically actionable germline variants, particularly for SNVs and small indels; however, a small subset of alterations affecting HRD, DDR and MMR genes may not be detected optimally. Therefore, for high-risk patients with negative tumor-only sequencing results, clinical genetic testing could be considered given the impact of these variants on therapy and genetic counseling.

Radiology volunteers to support a breast cancer screening program in Peru: description of the project, preliminary results, and impressions. / Voluntariado radiológico para apoyar un programa de detección precoz del cáncer de mama en Perú: descripción del proyecto, presentación de los primeros resultados e impresiones.

Breast cancer is the second most common cancer in Peruvian women. Due to limitations in national breast cancer screening programs, especially in rural areas, more than 50% of cases of breast cancer in Peru are diagnosed in advanced stages. In collaboration with a local clinic registered as a nongovernmental organization (CerviCusco), RAD-AID International aims to create a sustainable diagnostic structure to improve breast cancer screening in Cuzco. With the support of local, national, and international partners that have collaborated in analyzing radiological resources, raising awareness in the population, acquiring equipment, training clinical staff, and building referral networks, our teams of radiologists, included in the RAD-AID team, have participated in training CerviCusco staff in breast ultrasound, thus enabling additional training for radiology residents through a regulated international collaboration.

Comparison of mortality rate in older adults with and without functional awareness: the Neurological Disorders in Central Spain (NEDICES) population-based study.

OBJECTIVES: The main aim of the study was to compare the rates of mortality in older adults with and without functional unawareness (FU). We also tested a possible interaction effect between levels of awareness and education, as a single cognitive reserve proxy, on mortality. STUDY DESIGN: The study design is a longitudinal population-based cohort study. METHODS: The Neurological Disorders in Central Spain is epidemiological study to detect main age-associated conditions in people aged 65 years and older. Participants were collected from updated population-based registers of residents in three areas of central Spain. Awareness of functional limitations was established in accordance with the discrepancy between two sources of information on functional impairments: reliable informants versus the participants themselves. Three mutually exclusive groups were formed, namely, Functional Limitation Complaints (FCs), FU, and Functional Awareness (FA). Cox's regression models, adjusted by different covariates, were used to calculate the risk of mortality for each group at 5-year follow-up (vs. reference group without limitations). RESULTS: Of 1818 selected individuals, 229 (12.5%) showed FA, 254 (13.9%) showed FC, and 96 (5%) were classified as FU. All these groups showed an increased risk of mortality at 5-year follow-up [adjusted hazard ratio (HR) for FC < FU < FA]. However, the association of FU with mortality remained significant only for highly educated individuals. CONCLUSIONS: Functional impairment was associated with increased mortality rates, regardless of the presence of unawareness. This study extends the role of education in modulating the symptoms and prognosis of individuals at very mild or preclinical dementia stages.

Association between Parkinson's disease and diabetes: Data from NEDICES study.

BACKGROUND: Despite growing evidence showing an association between Parkinson's disease (PD) and diabetes, epidemiological studies have shown conflicting results. AIMS OF THE STUDY: To evaluate the association between PD and diabetes and the impact of diabetes duration in this association in an elderly (≥65 years) Spanish population. METHODS: Data for this cross-sectional population-based analysis were obtained from NEDICES study. Subjects were identified from census list. Diagnosis of PD was confirmed by neurological examination. Diabetes was defined by self-report, being on antidiabetic medication or diagnosis on medical records. Logistic regression analysis adjusted by potential confounders was performed to estimate the association between both conditions and also after dividing patients into short-duration (<10 years) and long-duration (≥10 years) diabetes. RESULTS: A total of 4998 subjects were included (79 PD and 4919 controls). Univariate analysis did not show any association between prevalence of PD and diabetes (OR 1.89, 95% CI 0.90-3.98, P=.09), although subgroup analysis showed a positive association in those with long-duration diabetes (3.27, 95% CI 1.21-8.85, P=.02). CONCLUSIONS: Diabetes duration might be an important factor in the association between PD and diabetes, and the risk might be limited to those with longer disease duration.

Cognition in non-demented Parkinson's disease vs essential tremor: A population-based study.

OBJECTIVES: Patients with Parkinson's disease (PD) and essential tremor (ET) have a higher risk of cognitive impairment than age-matched controls. Only a few small studies (11-18 subjects per group) have directly compared the cognitive profile of these conditions. Our aim was to compare the cognitive profile of patients with these two conditions to each other and to healthy individuals in a population-based study of non-demented participants. MATERIALS AND METHODS: This investigation was part of the NEDICES study, a survey of the elderly in which 2438 dementia-free participants underwent a short neuropsychological battery. We used nonparametric techniques to evaluate whether there are differences and/or a gradient of impairment across the groups (PD, ET, and controls). Also, we performed a head-to-head comparison of ET and PD, adjusting for age and education. RESULTS: Patients with PD (N=46) and ET (N=180) had poorer cognition than controls (N=2212). An impaired gradient of performance was evident. PD scored lower than ET, and then each of these lower than controls, in memory (P<.05) and verbal fluency (P<.001) tasks. When we compared PD and ET, the former had lower scores in verbal fluency (P<.05), whereas the later had a poorer cognitive processing speed (P<.05). CONCLUSIONS: This large population-based study demonstrates that both conditions influence cognitive performance, that a continuum exists from normal controls to ET to PD (most severe), and that although deficits are in many of the same cognitive domains, the affected cognitive domains do not overlap completely.

Alzheimer's disease prevention: A way forward. / Prevención de la enfermedad de Alzheimer: un camino a seguir.

This review proposes a more optimistic view of Alzheimer's disease (AD), in contrast to that contributed by the ageing of the population and the failure of potentially curative therapies (vaccines and others). Treatment failure is likely due to the fact that AD gestates in the brain for decades but manifests in old age. This review updates the concept of AD and presents the results of recent studies that show that primary prevention can reduce the incidence and delay the onset of the disease. Half of all cases of AD are potentially preventable through education, the control of cardiovascular risk factors, the promotion of healthy lifestyles and specific drug treatments. These approaches could substantially reduce the future incidence rate of this disease.

The 37 item Version of the Mini-Mental State Examination: Normative Data in a Population-Based Cohort of Older Spanish Adults (NEDICES).

The 37-item version of the Mini-Mental State Examination (MMSE-37) is an extended version of the original test for individuals with low education, which was adapted for different cultures. Despite its favorable psychometric properties, there is a lack of normative data for this instrument. We provide normative data for the MMSE-37 stratified by age, sex, and education in a large population-based cohort of older Spanish adults. The sample consisted of 3,777 participants without dementia (age range: 65-97 years) from different socioeconomic areas of central Spain. Normative data are presented in percentile ranks and divided into nine overlapping age tables with different midpoints, using the overlapping cell procedure. A hierarchical regression was performed to evaluate the effects of sociodemographic variables on MMSE-37 performance. Results showed that age, sex, and education affect test score. The norms presented herein are important for the correct interpretation of MMSE-37 scores when assessing older adults in Spain.

[Incidence and risk factors of venous thromboembolism in major spinal surgery with no chemical or mechanical prophylaxis]. / Incidencia y factores de riesgo de enfermedad tromboembólica venosa en cirugía mayor espinal, sin profilaxis química o mecánica.

OBJECTIVES: To evaluate the incidence of venous thromboembolism in spine surgery with no chemical and mechanical prophylaxis, and to determine the specific risk factors for this complication. MATERIALS AND METHODS: A historical cohort was analysed. All patients subjected to major spinal surgery, between January 2010 and September 2014, were included. No chemical or mechanical prophylaxis was administered in any patient. Active mobilisation of lower limbs was indicated immediately after surgery, and early ambulation started in the first 24-48 hours after surgery. Clinically symptomatic cases were confirmed by Doppler ultrasound of the lower limbs or chest CT angiography. RESULTS: A sample of 1092 cases was studied. Thromboembolic events were observed in 6 cases (.54%); 3 cases (.27%) with deep venous thrombosis and 3 cases (.27%) with pulmonary thromboembolism. A lethal case was identified (.09%). There were no cases of major bleeding or epidural haematoma. The following risk factors were identified: a multilevel fusion at more than 4 levels, surgeries longer than 130 minutes, patients older than 70 years of age, hypertension, and degenerative scoliosis. DISCUSSION: There is little scientific evidence on the prevention of thromboembolic events in spinal surgery. In addition to the disparity of prophylactic methods indicated by different specialists, it is important to weigh the risk-benefit of intra- and post-operative bleeding, and even the appearance of an epidural haematoma. Prophylaxis should be assessed in elderly patients over 70 years old, who are subjected to surgeries longer than 130 minutes, when 4 or more levels are involved.

Practical application of brief cognitive tests.

INTRODUCTION: Brief cognitive tests (BCT) may help detect cognitive impairment (CI) in the clinical setting. Several BCT have been developed and/or validated in our country, but we lack specific recommendations for use. DEVELOPMENT: Review of studies on the diagnostic accuracy of BCT for CI, using studies conducted in Spain with BCT which take less than 20 min. We provide recommendations of use based on expert consensus and established on the basis of BCT characteristics and study results. CONCLUSION: The Fototest, the Memory Impairment Screen (MIS) and the Mini-Mental State Examination (MMSE) are the preferred options in primary care; other BCT (Clock Drawing Test [CDT], test of verbal fluency [TVF]) may also be administered in cases of negative results with persistent suspected CI or concern (stepwise approach). In the specialised care setting, a systematic assessment of the different cognitive domains should be conducted using the Montreal Cognitive Assessment, the MMSE, the Rowland Universal Dementia Assessment, the Addenbrooke's Cognitive Examination, or by means of a stepwise or combined approach involving more simple tests (CDT, TVF, Fototest, MIS, Memory Alteration Test, Eurotest). Associating an informant questionnaire (IQ) with the BCT is superior to the BCT alone for the detection of CI. The choice of instruments will depend on the patient's characteristics, the clinician's experience, and available time. The BCT and IQ must reinforce - but never substitute - clinical judgment, patient-doctor communication, and inter-professional dialogue.

[Spanish versions of the Minimental State Examination (MMSE). Questions for their use in clinical practice]. / Versiones en español del Minimental State Examination (MMSE). Cuestiones para su uso en la practica clinica.

The Minimental State Examination (MMSE), created in 1975 as a tool for briefly evaluating the patient's mental state, has been widely used and is the most frequently cited cognitive test on Medline, as well as being the one with the most versions in different languages (over 70). Through a review of the Medline database, this paper aims to analyse its virtues and shortcomings, in addition to determining its current clinical usefulness, in both the original version and any of its modifications, although here we are mainly concerned with its Spanish adaptations. The MMSE (original or versions) is the most commonly used test for standardised cognitive assessment in the clinical setting, especially in the case of the elderly. It is the test with the most data for screening, staging and monitoring dementias. Yet, because filling it in may take over 10 minutes, it has to compete with shorter, more specific screening tests in the primary care and community setting. In the hospital and specialised setting, there is a need for broader standardised neuropsychological tests that make it possible to detect subtle cognitive disorders in patients with incipient dementia or mild cognitive impairment, as well as to establish a cognitive profile of the different subtypes of dementia. This study proposes a series of recommendations on the clinical use of the Spanish versions of the MMSE in different contexts of application.

TITLE: Versiones en español del Minimental State Examination (MMSE). Cuestiones para su uso en la practica clinica.El Minimental State Examination (MMSE), creado en 1975 como instrumento para la evaluacion breve del estado mental, ha tenido una gran difusion, y es el test cognitivo mas citado en Medline y con mayor numero de versiones idiomaticas (superiores a 70). Este articulo pretende, mediante una revision en la base de datos Medline, analizar sus virtudes y limitaciones, ademas de precisar su utilidad clinica actual, tanto de la version original como de sus modificaciones, principalmente de las adaptaciones al español. El MMSE (original o versiones) es el test mas utilizado para la evaluacion cognitiva estandarizada en el ambito clinico, sobre todo en el anciano. Es el que dispone de mas datos para el cribado, estadiaje y seguimiento de las demencias. Sin embargo, dado que su cumplimentacion puede requerir mas de 10 minutos, ha de competir con tests de cribado mas cortos y especificos en atencion primaria y el medio comunitario. En el ambito hospitalario y especializado, se precisan evaluaciones neuropsicologicas estandarizadas mas amplias que permitan detectar alteraciones cognitivas sutiles en pacientes con demencia incipiente o alteracion cognitiva leve, ademas de establecer un perfil cognitivo de los diferentes subtipos de demencias. Este trabajo realiza una serie de recomendaciones sobre el uso clinico de las versiones españolas del MMSE en diferentes contextos de aplicacion.

Queratoacantoma de vulva: presentación de un caso / Vulvar keratoacanthoma: presentation of a case

El queratoacantoma de vulva es una entidad rara que podría presentar confusión en su diagnóstico con el carcinoma bien diferenciado de células escamosas. Presentamos un caso de una paciente con diagnóstico de queratoacantoma de vulva tratada con resección quirúrgica de la lesión y su seguimiento posterior.

Vulvar keratoacanthoma is a rare disease that may present confusion in diagnosis with well differentiated squamous cell carcinoma. We report one patient with vulvar keratoacanthoma, treated by resection surgery of the lesion and her outcome.

Tumores virilizantes del ovario: presentación de dos casos manejados mediante cirugía por monopuerto / Virilizing tumors of the ovary: presentation of two cases managed by single-port surgery

Los tumores virilizantes, corresponden al 1% de todos los tumores funcionales del ovario. Estos tipos de tumores virilizantes se originan de las células pluri-potenciales del estroma ovárico, tienen la capacidad de secretar 17-hidroxiprogesterona, testosterona y androstenediona, desencadenando hiperandrogenismo clínico. Son catalogados como de bajo potencial maligno, con un patrón de crecimiento lento, bien diferenciados, diagnosticados en su mayoría en estadío I y II, de buen pronóstico y típicos de mujeres en edad reproductiva. El objetivo de esta comunicación es presentar dos casos clínicos con diagnóstico de tumor virilizante de ovario, tratadas con cirugía laparoscópica por mono puerto.

Virilizing tumors, corresponding to 1% of all functional ovarian tumors. Those type of virilizing tumors originate from pluripotential ovarian stromal cells and have the capacity to secrete 17-hydroxyprogesterone, testosterone and androstenedione, triggering clinical hyperandrogenism. They are classified as low malignant potential, well differentiated, with a pattern of slow growth, mostly diagnosed in stage I and II, with good prognosis and typical of women of reproductive age. The aim of this paper is to present two cases of virilizing ovarian tumor treated by mono port laparoscopic surgery.

Cause of death in mild cognitive impairment: a prospective study (NEDICES).

BACKGROUND AND PURPOSE: Previous studies have reported the occurrence of increased mortality rates among individuals with mild cognitive impairment (MCI), but possible links between MCI subtypes and cause-specific mortality need to be explored. To examine short-term mortality (5 years), long-term mortality (13 years) and cause-specific mortality of individuals over 65 years of age suffering from MCI compared with cognitively unimpaired individuals in the Neurological Disorders in Central Spain (NEDICES) cohort. METHODS: Mild cognitive impairment was classified using standardized psychometric and functional assessment in accordance with diagnostic convention. Cox's proportional hazards models, adjusted by sociodemographics and comorbidity factors, were used to assess the risk of death at 5 and 13 years of MCI subtypes compared with a reference group of older people without cognitive impairment (N = 2329). Causes of death were obtained from the National Population Register of Spain. RESULTS: There were 1484 deceased individuals at 13 years. MCI subtypes were defined as amnestic single domain (N = 259), amnestic multiple domain (N = 197) and non-amnestic (N = 641). After adjusting for covariates, only the amnestic multiple domain MCI subtype showed an increased hazard ratio (HR) for mortality at 5 years versus the reference group. However, the HR for mortality at 13 years was increased for all MCI subtypes. The HR by MCI subtype was 1.19 in the non-amnestic subtype (95% CI 1.05-1.36), 1.31 in the amnestic single domain subtype (95% CI 1.10-1.56) and 1.67 in the amnestic multiple domain subtype (95% CI 1.38-2.02). In terms of cause-specific mortality, the chance of death from dementia was statistically higher in all MCI subtypes. CONCLUSION: Amnestic multiple domain MCI showed the greatest risk of mortality in comparison with other MCI subtypes at different intervals. Dementia was the only cause-specific mortality that was increased in MCI individuals.

Cumulative effect of depression on dementia risk.

Objective. To analyze a potential cumulative effect of life-time depression on dementia and Alzheimer's disease (AD), with control of vascular factors (VFs). Methods. This study was a subanalysis of the Neurological Disorders in Central Spain (NEDICES) study. Past and present depression, VFs, dementia status, and dementia due to AD were documented at study inception. Dementia status was also documented after three years. Four groups were created according to baseline data: never depression (nD), past depression (pD), present depression (prD), and present and past depression (prpD). Logistic regression was used. Results. Data of 1,807 subjects were investigated at baseline (mean age 74.3, 59.3% women), and 1,376 (81.6%) subjects were evaluated after three years. The prevalence of dementia at baseline was 6.7%, and dementia incidence was 6.3%. An effect of depression was observed on dementia prevalence (OR [CI 95%] 1.84 [1.01-3.35] for prD and 2.73 [1.08-6.87] for prpD), and on dementia due to AD (OR 1.98 [0.98-3.99] for prD and OR 3.98 [1.48-10.71] for prpD) (fully adjusted models, nD as reference). Depression did not influence dementia incidence. Conclusions. Present depression and, particularly, present and past depression are associated with dementia at old age. Multiple mechanisms, including toxic effect of depression on hippocampal neurons, plausibly explain these associations.

Obesity and impaired cognitive functioning in the elderly: a population-based cross-sectional study (NEDICES).

BACKGROUND AND PURPOSE: Studies of high body mass index (BMI) and cognition in the elderly have shown conflicting results. While some studies have shown a detrimental effect of high BMI on cognitive function, others have observed beneficial effects on cognition. Our aim was to assess cognitive function in a large population-based sample of overweight (BMI 25-29.9 kg/m(2) ) and obese (BMI ≥ 30 kg/m(2) ) community-dwelling elderly participants compared with their counterparts with BMI < 25 kg/m(2) (i.e. controls) living in the same population. METHODS: One-thousand nine-hundred and forty-nine population-dwelling participants aged ≥ 65 years in central Spain [the Neurological Diseases in Central Spain study (NEDICES)] underwent a neuropsychological assessment, including tests of global cognitive performance [measured with a 37-item version of the Mini-Mental State Examination (37-MMSE)], psychomotor speed, verbal fluency, memory and pre-morbid intelligence. RESULTS: There were 507 with BMI < 25 kg/m(2) , 850 overweight and 592 obese participants. In regression analyses that adjusted for age, gender, educational category, intake of medications that potentially affect cognition function, diabetes mellitus, hypertension, dementia, ever smoker, ever drinker and waist circumference, we found that obese/overweight status was associated with the lowest quartiles of the 37-MMSE, Trail Making Test-A (number of errors; indeed more errors), verbal fluency, delayed free recall, immediate logical memory and pre-morbid intelligence. CONCLUSIONS: In this large population sample, overweight and obese participants performed poorer on formal neuropsychological tests than their counterparts with BMI < 25 kg/m(2) . These results support the hypothesis of a detrimental effect of high BMI on impaired cognition in the elderly.

Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression.

Once stimulated, the epidermal growth factor receptor (EGFR) undergoes self-phosphorylation, which, on the one hand, instigates signaling cascades, and on the other hand, recruits CBL ubiquitin ligases, which mark EGFRs for degradation. Using RNA interference screens, we identified a deubiquitinating enzyme, Cezanne-1, that opposes receptor degradation and enhances EGFR signaling. These functions require the catalytic- and ubiquitin-binding domains of Cezanne-1, and they involve physical interactions and transphosphorylation of Cezanne-1 by EGFR. In line with the ability of Cezanne-1 to augment EGF-induced growth and migration signals, the enzyme is overexpressed in breast cancer. Congruently, the corresponding gene is amplified in approximately one third of mammary tumors, and high transcript levels predict an aggressive disease course. In conclusion, deubiquitination by Cezanne-1 curtails degradation of growth factor receptors, thereby promotes oncogenic growth signals.