Anderson Cancer Center Madrid

Spain

Anderson Cancer Center Madrid

Spain
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PubMed | Health Research Institute of Santiago IDIS, Autonomous University of Barcelona, University of Lleida, Autonomous University of Madrid and 4 more.
Type: Journal Article | Journal: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | Year: 2016

Endometrial cancer is the most common cancer of the female genital tract in developed countries. Although the majority of endometrial cancers are diagnosed at early stages and the 5-year overall survival is around 80%, early detection of these tumors is crucial to improve the survival of patients given that the advanced tumors are associated with a poor outcome. Furthermore, correct assessment of the pre-clinical diagnosis is decisive to guide the surgical treatment and management of the patient. In this sense, the potential of targeted genetic sequencing of uterine aspirates has been assessed as a pre-operative tool to obtain reliable information regarding the mutational profile of a given tumor, even in samples that are not histologically classifiable. A total of 83 paired samples were sequenced (uterine aspirates and hysterectomy specimens), including 62 endometrioid and non-endometrioid tumors, 10 cases of atypical hyperplasia and 11 non-cancerous endometrial disorders. Even though diagnosing endometrial cancer based exclusively on genetic alterations is currently unfeasible, mutations were mainly found in uterine aspirates from malignant disorders, suggesting its potential in the near future for supporting the standard histologic diagnosis. Moreover, this approach provides the first evidence of the high intra-tumor genetic heterogeneity associated with endometrial cancer, evident when multiple regions of tumors are analyzed from an individual hysterectomy. Notably, the genetic analysis of uterine aspirates captures this heterogeneity, solving the potential problem of incomplete genetic characterization when a single tumor biopsy is analyzed.


PubMed | Hospital del Mar and Institute Josep Carreras IJC, Hospital del Mar, Hospital Clinico Of Salamanca, Hospital Xeral Cies and 14 more.
Type: Journal Article | Journal: Leukemia | Year: 2014

Splenic marginal zone lymphoma (SMZL) is a B-cell neoplasm whose molecular pathogenesis remains fundamentally unexplained, requiring more precise diagnostic markers. Previous molecular studies have revealed 7q loss and mutations of nuclear factor B (NF-B), B-cell receptor (BCR) and Notch signalling genes. We performed whole-exome sequencing in a series of SMZL cases. Results confirmed that SMZL is an entity distinct from other low-grade B-cell lymphomas, and identified mutations in multiple genes involved in marginal zone development, and others involved in NF-B, BCR, chromatin remodelling and the cytoskeleton.


PubMed | The Royal Marsden NHS Foundation Trust, University of Lyon, Innsbruck Medical University, Leiden University and 6 more.
Type: | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2016

Traditionally, BRCA genetic testing has been undertaken to identify patients and family members at future risk of developing cancer and patients have been referred for testing based on family history. However, the now recognised risk of ovarian cancer (OC) patients, even those with no known family history, harbouring a mutation in BRCA1/2, together with the first poly adenosine diphosphateribose polymerase inhibitor (PARPi; olaparib [Lynparza]) being licenced for the treatment of BRCA-mutated OC, has led to reconsideration of referral criteria for OC patients. Provided here is a review of the existing data and guidelines in the European Union, relating to recommendations, as well as considerations, for the referral of OC patients for BRCA genetic testing. Based on this review of newly updated guidance and up-to-date evidence, the following is recommended: all patients with invasive epithelial OC (excluding borderline or mucinous), including those with fallopian tube and peritoneal cancers, should be considered as candidates for referral for BRCA genetic testing, irrespective of age; genetic testing should ideally be offered at diagnosis, although patients can be referred at any stage; retrospective testing should be offered to patients in long-term follow-up because of the implications for family members and individual future breast cancer risk; and germline BRCA testing of a blood/saliva sample should initially be conducted and, if negative, tumour tissue should be tested (to identify non-germline [somatic] BRCA PARPi therapy candidates).


Cascon A.,Hereditary Endocrine Cancer Group | Cascon A.,Research Center Biomedica En Red Of Enfermedades Raras | Comino-Mendez I.,Hereditary Endocrine Cancer Group | Curras-Freixes M.,Hereditary Endocrine Cancer Group | And 31 more authors.
Journal of the National Cancer Institute | Year: 2015

Disruption of the Krebs cycle is a hallmark of cancer. IDH1 and IDH2 mutations are found in many neoplasms, and germline alterations in SDH genes and FH predispose to pheochromocytoma/paraganglioma and other cancers. We describe a paraganglioma family carrying a germline mutation in MDH2, which encodes a Krebs cycle enzyme. Whole-exome sequencing was applied to tumor DNA obtained from a man age 55 years diagnosed with multiple malignant paragangliomas. Data were analyzed with the two-sided Student's t and Mann-Whitney U tests with Bonferroni correction for multiple comparisons. Between six-and 14-fold lower levels of MDH2 expression were observed in MDH2-mutated tumors compared with control patients. Knockdown (KD) of MDH2 in HeLa cells by shRNA triggered the accumulation of both malate (mean ± SD: wild-type [WT] = 1±0.18; KD = 2.24±0.17, P =. 043) and fumarate (WT = 1±0.06; KD = 2.6±0.25, P =. 033), which was reversed by transient introduction of WT MDH2 cDNA. Segregation of the mutation with disease and absence of MDH2 in mutated tumors revealed MDH2 as a novel pheochromocytoma/paraganglioma susceptibility gene. © 2015 © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.


Cubillo E.,Autonomous University of Madrid | Cubillo E.,Instituto Nacional Of Toxicologia Y Ciencias Forenses Intcf | Diaz-Lopez A.,Autonomous University of Madrid | Cuevas E.P.,Autonomous University of Madrid | And 8 more authors.
PLoS ONE | Year: 2013

E12/E47 proteins (encoded by E2A gene) are members of the class I basic helix-loop-helix (bHLH) transcription factors (also known as E proteins). E47 has been described as repressor of E-cadherin and inducer of epithelial-mesenchymal transition (EMT). We reported previously that EMT mediated by E47 in MDCK cells occurs with a concomitant overexpression of Id1 and Id3 proteins. Id proteins belong to class V of HLH factors that lack the basic domain; they dimerise with E proteins and prevent their DNA interaction, thus, acting as dominant negative of E proteins. Here, we show that E47 interacts with Id1 in E47 overexpressing MDCK cells that underwent a full EMT as well as in mesenchymal breast carcinoma and melanoma cell lines. By conducting chromatin immunoprecipitation assays we demonstrate that E47 binds directly to the endogenous E-cadherin promoter of mesenchymal MDCK-E47 cells in a complex devoid of Id1. Importantly, our data suggest that both E47 and Id1 are required to maintain the mesenchymal phenotype of MDCK-E47 cells. These data support the collaboration between E47 and Id1 in the maintenance of EMT by mechanisms independent of the dominant negative action of Id1 on E47 binding to E-cadherin promoter. Finally, the analysis of several N0 breast tumour series indicates that the expression of E47 and ID1 is significantly associated with the basal-like phenotype supporting the biological significance of the present findings. © 2013 Cubillo et al.


PubMed | Complexo Hospitalario Universitario Of runa, Vithas Nuestra Senora Of America Hospital, Henares University Hospital, Mostoles University and 2 more.
Type: Journal Article | Journal: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery | Year: 2016

The minimally invasive total laryngectomy avoids a wide surgical field and so it has the potential benefit of reducing the local morbidity, especially on radiated patients. This approach has been previously described on a robotic basis, the transoral robotic total laryngectomy (TORS-TL). We have designed a minimally invasive approach for total laryngectomy (TL) using the transoral ultrasonic surgery technique (TOUSS). TOUSS is a transoral, endoscopic, non-robotic approach for laryngeal and pharyngeal tumors, based on the ultrasonic scalpel as a resection tool. Two patients with a laryngeal squamous cell carcinoma with indication for total laryngectomy were surgically treated: one primary TL for a subglottic carcinoma and one salvage TL with partial pharyngectomy for a local relapse after chemoradiotherapy of a glottic carcinoma. The tumors were completely removed with free surgical margin in both patients. The functional recovery was satisfactory in terms of swallowing and speech (a tracheoesophageal puncture and voice prosthesis placement were done in the same procedure). No intraoperative complications were observed. The patient with previous chemoradiotherapy had a pharyngocutaneous fistula which closed spontaneously without additional surgery. We have demonstrated that transoral endoscopic approach to the larynx and pharynx is feasible without a robotic platform. TOUSS-TL can easily spread the transoral endoscopic philosophy as well as the benefits of a minimally invasive way to remove the entire larynx. Further research will show the advantages in terms of complications and functional outcomes.


Moreno-Bueno G.,Research Institute Biomedicas Alberto Sols | Moreno-Bueno G.,Anderson Cancer Center Madrid | Salvador F.,Research Institute Biomedicas Alberto Sols | Martin A.,Research Institute Biomedicas Alberto Sols | And 15 more authors.
EMBO Molecular Medicine | Year: 2011

Basal-like breast carcinoma is characterized by the expression of basal/myoepithelial markers, undifferentiated phenotype, highly aggressive behaviour and frequent triple negative status (ESR-, PR-, Her2neu-). We have previously shown that epithelial-mesenchymal transition (EMT) occurs in basal-like breast tumours and identified Lysyl-oxidase-like 2 (LOXL2) as an EMT player and poor prognosis marker in squamous cell carcinomas. We now show that LOXL2 mRNA is overexpressed in basal-like human breast carcinomas. Breast carcinoma cell lines with basal-like phenotype show a specific cytoplasmic/perinuclear LOXL2 expression, and this subcellular distribution is significantly associated with distant metastatic incidence in basal-like breast carcinomas. LOXL2 silencing in basal-like carcinoma cells induces a mesenchymal-epithelial transition (MET) associated with a decrease of tumourigenicity and suppression of metastatic potential. Mechanistic studies indicate that LOXL2 maintains the mesenchymal phenotype of basal-like carcinoma cells by a novel mechanism involving transcriptional downregulation of Lgl2 and claudin1 and disorganization of cell polarity and tight junction complexes. Therefore, intracellular LOXL2 is a new candidate marker of basal-like carcinomas and a target to block metastatic dissemination of this aggressive breast tumour subtype. © 2011 EMBO Molecular Medicine.


We aimed to define the clinicopathological characteristics of 29 primary sinonasal diffuse large B cell lymphoma (DLBCLIn the training set, 82% had a non-germinal center B-cell-like (Hans Classifier) (non-GCB) phenotype and 18% were Epstein-Barr virus-encoded small RNAs (EBER)DLBCL


Chiva L.M.,Anderson Cancer Center Madrid | Gonzalez-Martin A.,Anderson Cancer Center Madrid
Gynecologic Oncology | Year: 2014

Objective: Our objective was to review the published experiences of the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of advanced and recurrent ovarian cancer with a focus on survival outcomes. Methods: A search of the PubMed database (2008-2014) for articles specifically addressing the topic “HIPEC and ovarian cancer“ was performed. We found a total of 22 publications that included 1450 patients. A final group of eleven studies (248 patients with advanced ovarian cancer) and eight publications (499 patients with recurrent sensitive ovarian cancer) that included information about survival were reviewed. Results: Among patients with primary ovarian cancer who were treated with primary debulking and HIPEC, the weighted median overall survival was 37.3. months (range 27-78), the median disease-free survival was 14.4. months (range 12-30), and the 5-yr-survival rate was 40% (range 28-72). In the recurrent cohort, the overall survival after HIPEC was 36.5. months (range 23-62), and the median disease-free survival was 20.2. months (range 11-29). The rates of severe morbidity were 25 and 19% in the primary and recurrent groups, respectively. Conclusion: Although randomized trials are ongoing, the recently published retrospective data regarding the use of HIPEC for primary advanced and for recurrent ovarian cancer do not indicate any apparent advantage of this treatment in terms of the survival outcomes in these patients. Therefore, HIPEC cannot be considered a standard treatment and should not be offered outside of clinical trials. © 2014 Elsevier Inc.

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