Artículos (Citología e Histología Normal y Patológica)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/11005

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The PARP inhibitor olaparib enhances the sensitivity of Ewing sarcoma to trabectedin
(Impact Journals LLC, 2017-05-27) Ordóñez, José Luis; Amaral, Ana Teresa; Carcaboso, Ángel M.; Herrero-Martin, David; García-Macías, María del Carmen; Sevillano, Vicky; Álava Casado, Enrique de; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Gobierno de España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Instituto de Salud Carlos III; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
Recent preclinical evidence has suggested that Ewing Sarcoma (ES) bearing EWSR1-ETS fusions could be particularly sensitive to PARP inhibitors (PARPinh) in combination with DNA damage repair (DDR) agents. Trabectedin is an antitumoral agent that modulates EWSR1-FLI1 transcriptional functions, causing DNA damage. Interestingly, PARP1 is also a transcriptional regulator of EWSR1-FLI1, and PARPinh disrupts the DDR machinery. Thus, given the impact and apparent specificity of both agents with regard to the DNA damage/DDR system and EWSR1-FLI1 activity in ES, we decided to explore the activity of combining PARPinh and Trabectedin in in vitro and in vivo experiments. The combination of Olaparib and Trabectedin was found to be highly synergistic, inhibiting cell proliferation, inducing apoptosis, and the accumulation of G2/M. The drug combination also enhanced γH2AX intranuclear accumulation as a result of DNA damage induction, DNA fragmentation and global DDR deregulation, while EWSR1-FLI1 target expression remained unaffected. The effect of the drug combination was corroborated in a mouse xenograft model of ES and, more importantly, in two ES patient-derived xenograft (PDX) models in which the tumors showed complete regression. In conclusion, the combination of the two agents leads to a biologically significant deregulation of the DDR machinery that elicits relevant antitumor activity in preclinical models and might represent a promising therapeutic tool that should be further explored for translation to the clinical setting.
Evaluating the anti-inflammatory and antioxidant efficacy of complementary andalternative medicines (CAM) used for management of inflammatory bowel disease:a comprehensive review
(Taylor & Francis, 2025-03-08) Shin, Sia; Xie, Kangzhe; Duhun, Suehad Abou; Ortiz Cerda, Tamara Andrea; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica
beenfullyelucidated,andcurrenttreatmentsarenotdefinitiveandoftencarryseveralsideeffects. The Complementary andAlternativeMedicine (CAM) offers a newapproach to conventional medicine.However, theirclinicalapplicationandmechanismsremainlimited. Objective:Theaimof thisreviewistoevaluatetheanti-inflammatory, impactonmicrobiotaand antioxidantefficacyofcurrentlyavailableCAMfor IBD. Methods:TheliteraturecollectionwasobtainedfromGoogleScholar,MEDLINE,PubMedandWebof Science(WOS).Studiesinbothhumanandanimalmodels,publishedinEnglishlanguagebetween 2018 and 2024, were selected. Sixty-seven studieswere included in the current reviewafter inclusionandexclusionscreeningprocesses. Results:Mostly,studiesshowedsignificantanti-inflammatory,gutmicrobiotarestoring,antioxidant effectsofpolyphenols,polysaccharides, emodin, short-chainfattyacids (SCFA; includingbutyrate, propionateandacetate), andprobiotics althoughsomecontrasting resultswerenoted. Current evidence shows that polyphenols exhibit the most consistent result in alleviating IBD pathophysiology,primarilyduetotheirsignificantSCFA-elevatingeffect. Discussion:Futurestudiesmayfocusonhumanstudies,narrowingdownonindividualfactorswhich maychangenatural product’smetabolism. Further researchstudies arealsoessential toobtain therapeuticrecommendations.
Carcinoma de células basales queloideo
(Aula Médica Ediciones, 2015) Torres Gómez, Francisco Javier; Torres Olivera, Francisco Javier; Torres Gómez, Amelia; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS949: Biopatología y Estrés Oxidativo
El carcinoma de células basales es la neoplasia maligna más frecuente en humanos. Se han descrito múltiples variantes morfológicas con distintas implicaciones pronósticas. La variante queloidea ha sido referida en la literatura en contadas ocasiones. La intensa reacción fibrosa estromal de tipo queloideo obliga a plantear diagnósticos diferenciales con procesos cicatriciales. La seriación sistemática de la lesión y la identificación del componente neoplásico tipo carcinoma serán claves para establecer el diagnóstico.
Alpha-catenin-dependent recruitment of the centrosomal protein cap350 to adherens junctions allows epithelial cells to acquire a columnar shape
(Public Library Science, 2015-03-12) Gavilán Dorronzoro, María de la Paz; Arjona, Marina; Zurbano, Ángel; Formstecher, Etienne; Martinez-Morales, Juan R.; Bornens, Michel; Rios, Rosa M.; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Junta de Andalucía; Gobierno de España
Abstract Epithelial morphogenesis involves a dramatic reorganisation of the microtubule cytoskele ton. How this complex process is controlled at the molecular level is still largely unknown. Here, wereport that the centrosomal microtubule (MT)-binding protein CAP350 localises at adherens junctions in epithelial cells. By two-hybrid screening, we identified a direct interaction of AP350with the adhesion protein α-catenin that was further confirmed by co-immunoprecipitation experiments. Block of epithelial cadherin (E-cadherin)-mediated cell-cell adhesion or α-catenin depletion prevented CAP350 localisation at cell-cell junctions. Knocking downjunction-located CAP350 inhibited the establishment of an apico-basal array of microtubules and impaired the acquisition of columnar shape in Madin-Darby canine kidney II (MDCKII) cells grown as polarised epithelia. Furthermore, MDCKII cystogenesis was also defective in junctional CAP350-depleted cells. CAP350-depleted MDCKII cysts were smaller and contained either multiple lumens or no lumen. Membrane polarity wasnotaffected, but cortical microtubule bundles did not properly form. Our results indicate that CAP350mayactasanadaptorbetweenadherensjunctions and microtubules, thus regulating epithelial differentiation and contributing to the definition of cell architecture. We also uncover a central role of α-catenin in global cytoskeleton remodelling, in which it acts not only on actin but also on MT reorganisation during epithelial morphogenesis.
Proteomic profiling of ewing sarcoma reveals a role for traf6 in proliferation and ribonucleoproteins/rna processing
(Omics Publishing Group, 2016) Madoz-Gúrpide, Juan; Herrero Martín, David; Gómez López, Gonzalo; Hontecillas Prieto, Lourdes; Biscuola, Michele; Chamizo, Cristina; García Domínguez, Daniel José; Marcilla, David; Amaral, Ana Teresa; Ordoñez, José Luis; Álava Casado, Enrique de; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
Notwithstanding advances over the last decade in the comprehension of the molecular biology of Ewing sarcoma (ES), we still lack an understanding of critical issues, especially those regarding its genesis. In particular, little effort has been devoted to characterization of the proteic component of the mechanisms and pathways deployed by the activation of the fusion protein resulting from chromosomal translocation. We decided to investigate the proteic alterations of an ES cell line bearing a representative fusion protein. The combination of RNA interference of EWS FLI1 in the ES cell line TC-71, a proteomic analysis by 2-D electrophoresis and subsequent mass-spectrometry identification, and a global overrepresentation study detected changes in more than 500 spots. Forty-three proteins were identified as being significantly differentially abundant. As expected, we found and validated changes in proteins linked to nucleotide processing, transcription regulation, ribonucleoproteins, helicases, cell-cycle control and proliferation, and metabolic processes. Additionally, TNF receptor-associated factor 6 was revealed as a hub node. Our strategy showed the potential to reveal the protein interplay associated with the known functions of the fusion protein: binding to DNA and RNA in order to act as aberrant transcription factors or potent repressors, or by altering RNA processing.
Hibernoma de cavidad oral. Una entidad infrecuente
(Ediciones Ergon S.A; Sociedad Española de Cirugía Oral y Maxilofacial, 2015-01-19) Torres Gómez, Francisco Javier; Torres Gómez, Amelia; Torres Olivera, Francisco Javier; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS949: Biopatología y Estrés Oxidativo
El hibernoma es un tumor adiposo benigno que morfológicamente rememora la grasa fetal. Su presencia a nivel oral es excepcional. Presentamos un caso de hibernoma de cavidad oral, revisamos la entidad y mostramos los distintos diagnósticos diferenciales.
Characterization of Human Mesenchymal Stem Cells from Ewing Sarcoma Patients. Pathogenetic Implications
(Public Library of Science, 2014-02-03) Amaral, Ana Teresa; Manara, María Cristina; Berghuis, Dagmar; Ordoñez, José Luis; Biscuola, Michele; Lóez García, María Ángeles; Osuna, Daniel; Lucarelli, Enrico; Alviano, Francesco; Lankester, Arjan; Scotlandi, Katia; Álava Casado, Enrique de; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Italian Association for cancer research; Red Temática de Investigación del Cáncer
Background Ewing Sarcoma (EWS) is a mesenchymal-derived tumor that generally arises in bone and soft tissue. Intensive research regarding the pathogenesis of EWS has been insufficient to pinpoint the early events of Ewing sarcomagenesis. However, the Mesenchymal Stem Cell (MSC) is currently accepted as the most probable cell of origin. Materials and Methods In an initial study regarding a deep characterization of MSC obtained specifically from EWS patients (MSC-P), we compared them with MSC derived from healthy donors (MSC-HD) and EWS cell lines. We evaluated the presence of the EWS-FLI1 gene fusion and EWSR1 gene rearrangements in MSC-P. The presence of the EWS transcript was confirmed by q-RT-PCR. In order to determine early events possibly involved in malignant transformation, we used a multiparameter quantitative strategy that included both MSC immunophenotypic negative/positive markers, and EWS intrinsic phenotypical features. Markers CD105, CD90, CD34 and CD45 were confirmed in EWS samples. Results We determined that MSC-P lack the most prevalent gene fusion, EWSR1-FLI1 as well as EWSR1 gene rearrangements. Our study also revealed that MSC-P are more alike to MSC-HD than to EWS cells. Nonetheless, we also observed that EWS cells had a few overlapping features with MSC. As a relevant example, also MSC showed CD99 expression, hallmark of EWS diagnosis. However, we observed that, in contrast to EWS cells, MSC were not sensitive to the inhibition of CD99. Conclusions In conclusion, our results suggest that MSC from EWS patients behave like MSC-HD and are phenotypically different from EWS cells, thus raising important questions regarding MSC role in sarcomagenesis.
Clathrin-Mediated Endocytosis Is Impaired in Type A–B Niemann–Pick Disease Model Cells and Can Be Restored by ICAM-1-Mediated Enzyme Replacement
(American Chemical Society, 2014-06-20) Rappaport, Jeff; Garnacho Montero, Carmen; Muro, Silvia; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; NIH; National Science Foundation (NSF). United States; University of Maryland
Drugs often use endocytosis to achieve intracellular delivery, either by passive uptake from the extracellular fluid or by active targeting of cell surface features such as endocytic receptors. An example is enzyme replacement therapy, a clinically practiced treatment for several lysosomal storage diseases where glycosylated recombinant enzymes naturally target the mannose-6-phosphate receptor and are internalized by clathrin mediated endocytosis (CME). However, lysosomal substrate accumulation, a hallmark of these diseases, has been indirectly linked to aberrant endocytic activity. These effects are poorly understood, creating an obstacle to therapeutic efficiency. Here we explored endocytic activity in fibroblasts from patients with type A Niemann–Pick disease, a lysosomal storage disease characterized by acid sphingomyelinase (ASM) deficiency. The uptake of fluid phase markers and clathrin-associated ligands, formation of endocytic structures, and recruitment of intracellular clathrin to ligand binding sites were all altered, demonstrating aberrant CME in these cells. Model polymer nanocarriers targeted to intercellular adhesion molecule-1 (ICAM-1), which are internalized by a clathrin-independent route, enhanced the intracellular delivery of recombinant ASM more than 10-fold compared to free enzyme. This strategy reduced substrate accumulation and restored clathrin endocytic activity to wild-type levels. There appears to be a relationship between lysosomal storage and diminished CME, and bypassing this pathway by targeting ICAM-1 may enhance future therapies for lysosomal storage diseases.
Concrescencia clínica pero no histológica: presentación de un caso clínico
(Ediciones Ergon S.A, 2016) López Frías, Francisco Javier; Alonso-Ezpeleta, Óscar; Moreno-Fernández, Ana María; Armas Padrón, José Ramón; Jiménez Sánchez, María del Carmen; Segura Egea, Juan José; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Estomatología; Universidad de Sevilla. CTS941: Patología Dentaria, Operatoria Dental y Endodoncia
La concrescencia es una anomalía dentaria poco frecuente que se define como la unión de las raíces de dos dientes adyacentes a través del cemento. Aunque en la práctica clínica el término “concrescencia” es utilizado para referirse a todos los casos de unión entre las raíces de dos dientes adyacentes, para confirmar el diagnóstico de concrescencia es necesario un estudio histológico que demuestre la unión a nivel del cemento. Esta anomalía se ha identificado en el 0,8% de los casos de exodoncia de dientes permanentes, siendo su incidencia mayor en la región posterior del maxilar superior. La detección previa de la concrescencia mediante la exploración clínica y radiográfica es, la mayoría de las ocasiones, casi imposible, por lo que el diagnostico suele hacerse después de la extracción. No obstante, es conveniente que el clínico evalúe cada paciente y cada diente de forma exhaustiva para poder planificar, caso de que exista concrescencia, la técnica quirúrgica adecuada para la extracción. Por lo tanto, deben conocerse la incidencia e implicaciones de esta anomalía para llevar a cabo un diagnóstico y plan de tratamiento correcto. En este artículo se presenta un caso clínico de aparente concrescencia diagnosticado post-extracción y cuyo estudio histológico no mostró unión de cemento entre ambas raíces. Por lo tanto, en la práctica clínica es más conveniente utilizar el término “raíces fusionadas” que “concrescencia”, el cual sólo debería ser utilizado después del examen histológico de la pieza extraída.
Head and neck cancer. an aetiopathogenetic study of non-endemic lymphoepithelioma
(Pacini Editore Medicina, 2013-03) Casco, F.G.; Ríos, M.J.; Miguel Rodríguez, Manuel de; González, T.; Moreno-Fernández, Ana María; Galera Ruiz, Hugo; González Campora, Ricardo; Drut, R.; Bacchi, C.; Galera Davidson, Hugo; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. Departamento de Cirugía
An aetiopathogenetic analysis of non-endemic nasopharyngeal carcinoma (NPC) in European and Southern American patient groups was performed. Specifically, the study sought to determine the proportion of Epstein-Barr Virus (EBV)-positive tumour cells in NPC patients in two very different populations (Europe and South America) in areas not associated with a high incidence of NPC. Clinical data (age, sex and onset of clinical disease) were also analyzed. A total of 50 NPC samples, 24 from a European hospital (EH) and 26 from two South American hospitals (SAH), were included. Nuclear staining for Epstein-Barr virus–encoded small RNA (EBER) was performed by in situ hybridization (ISH). Latent membrane protein 1 (LMP1) expression was measured by immunohistochemical (IHC) analysis. A higher incidence of NPC was observed in patients > 40 years of age in EH; in SAH, by contrast, the incidence was higher in patients aged ≤ 40 years. Cervical lymph node metastasis was detected in 31 patients (of whom 84.6% were from SAH). A total of 72% of samples were EBERpositive; the incidence of EBER positivity was greater in type 3 NPCs. EBV was detected in a large proportion of epithelial cells in samples from both EH and SAH (75% vs. 69.2%, respectively). An association was found between EBER detection in lymphocytes and patient origin (p = 0.0001). LMP1 expression was detected in 64% of patients. ISH for the detection of EBER is the most sensitive technique for demonstrating EBV in tumour tissue. The incidence of EBV was not significantly greater in either of the study populations, but was significantly higher in patients with type 3 NPC. Definitive histological diagnosis of NPC was reached earlier in EH than in SAH, where metastases were more frequently diagnosed, suggesting that the disease had reached a more advanced stage by the time treatment was started
Clinical practice guidelines for the diagnosis and treatment of patients with soft tissue sarcoma by the Spanish group for research in sarcomas (GEIS)
(Springer, 2015-11-12) García del Muro, Xavier; Álava Casado, Enrique de; Artigas, V.; Bague, Silvia; Braña, Alejandro; Cubedo, Ricardo; Martin-Broto, Javier; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
Soft tissue sarcomas (STS) constitute an uncommon and heterogeneous group of tumours, which require a complex and specialized multidisciplinary management. The diagnostic approach should include imaging studies and core needle biopsy performed prior to undertaking surgery. Wide excision is the mainstay of treatment for localized sarcoma, and associated preoperative or postoperative radiotherapy should be administered in high-risk patients. Adjuvant chemotherapy was associated with a modest improvement in survival in a meta-analysis and constitutes a standard option in selected patients with high-risk STS. In metastatic patients, surgery must be evaluated in selected cases. In the rest of patients, chemotherapy and, in some subtypes, targeted therapy often used in a sequential strategy constitutes the treatment of election. Despite important advances in the understanding of the pathophysiology of the disease, the advances achieved in therapeutic results may be deemed still insufficient. Moreover, due to the rarity and complexity of the disease, the results in clinical practice are not always optimal. For this reason, the Spanish Group for Research on Sarcoma (GEIS) has developed a multidisciplinary clinical practice guidelines document, with the aim of facilitating the diagnosis and treatment of these patients in Spain. In the document, each practical recommendation is accompanied by level of evidence and grade of recommendation on the basis of the available data.
Proposal for the creation of a national strategy for precision medicine in cancer: a position statement of SEOM, SEAP and SEFH
(Editorial Garsi; Elsevier Science Inc., 2017) Garrido, Pilar; Aldaz, Azucena; Calleja, Miguel Ángel; Álava Casado, Enrique de; Lamas, María Jesús; Martín, Miguel; Matías-Guiu, Xavier; Palacios, José; Vera, Ruth; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Precision medicine is transforming clinical and biomedical research, as well as health care itself from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical-legal, regulatory, organizational and knowledge-related challenges. Without a national strategy, precision medicine, which will be implemented one way or another, could take place without the appropriate planning that can guarantee technical quality, equal access of all citizens to the best practices, violating the rights of patients and professionals and jeopardizing the solvency of the healthcare system. With this paper from the Spanish Societies of Medical Oncology (SEOM), Pathology (SEAP), and Hospital Pharmacy (SEFH) we highlight the need to institute a consensual national strategy for the development of precision medicine in our country, review the national and international context, comment on the opportunities and challenges for implementing precision medicine, and outline the objectives of a national strategy on precision medicine in cancer.
Robust diagnosis of Ewing sarcoma by immunohistochemical detection of super-enhancer-driven EWSR1-ETS targets
(Impact journals LLC, 2017-07-04) Baldauf, Michaela C.; Orth, Martin F.; Dallmayer, Marlene; Marchetto, Aruna; Gerke, Julia S.; Rubio, Rebeca Alba; Álava Casado, Enrique de; Grünewald, Thomas G.P.; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
Ewing sarcoma is an undifferentiated small-round-cell sarcoma. Although molecular detection of pathognomonic EWSR1-ETS fusions such as EWSR1-FLI1 enables definitive diagnosis, substantial confusion can arise if molecular diagnostics are unavailable. Diagnosis based on the conventional immunohistochemical marker CD99 is unreliable due to its abundant expression in morphological mimics. To identify novel diagnostic immunohistochemical markers for Ewing sarcoma, we performed comparative expression analyses in 768 tumors representing 21 entities including Ewing-like sarcomas, which confirmed that CIC-DUX4-, BCOR-CCNB3-, EWSR1-NFATc2-, and EWSR1-ETS-translocated sarcomas are distinct entities, and revealed that ATP1A1, BCL11B, and GLG1 constitute specific markers for Ewing sarcoma. Their high expression was validated by immunohistochemistry and proved to depend on EWSR1-FLI1-binding to highly active proximal super-enhancers. Automated cut-off-finding and combination-testing in a tissue-microarray comprising 174 samples demonstrated that detection of high BCL11B and/or GLG1 expression is sufficient to reach 96% specificity for Ewing sarcoma. While 88% of tested Ewing-like sarcomas displayed strong CD99-immunoreactivity, none displayed combined strong BCL11B- and GLG1-immunoreactivity. Collectively, we show that ATP1A1, BCL11B, and GLG1 are EWSR1-FLI1 targets, of which BCL11B and GLG1 offer a fast, simple, and cost-efficient way to diagnose Ewing sarcoma by immunohistochemistry. These markers may significantly reduce the number of misdiagnosed patients, and thus improve patient care.
Proposal for the creation of a national strategy for precision medicine in cancer: a position statement of SEOM, SEAP, and SEFH
(Springer, 2017-08-31) Garrido, Pilar; Aldaz, Azucena; Vera, Ruth; Calleja, Miguel Ángel; Álava Casado, Enrique de; Martín, M.; Matías-Guiu, Xavier; Palacios, José; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
Precision medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person. Precision medicine is transforming clinical and biomedical research, as well as health care itself from a conceptual, as well as a methodological viewpoint, providing extraordinary opportunities to improve public health and lower the costs of the healthcare system. However, the implementation of precision medicine poses ethical–legal, regulatory, organizational, and knowledge-related chal lenges. Without a national strategy, precision medicine, which will be implemented one way or another, could take place without the appropriate planning that can guarantee technical quality, equal access of all citizens to the best practices, violating the rights of patients and professionals, and jeopardizing the solvency of the healthcare system. With this paper from the Spanish Societies of Medical Oncology, Pathology, and Hospital Pharmacy, we highlight the need to institute a consensual national strategy for the development of precision medicine in our country, review the national and international context, comment on the opportunities and challenges for implementing precision medicine, and outline the objectives of a national strategy on precision medicine in cancer.
Sarcoma european and latin american network (SELNET) Recommendations on pioritization in sarcoma care during the COVID-19 pandemic
(Alphamed press, 2020) Martin-Broto, Javier; Hindi, Nadia; Aguiar, Samuel; Badilla-González, Ronald; Castro-Oliden, Victor; Chacón, Matias; Correa-Generoso, Raquel; Álava Casado, Enrique de; Muñoz Casares, Francisco Cristóbal; Federico; Blay, Jean Yves; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Unión Europea; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
Background. The COVID-19 outbreak has resulted in collision betweenpatientsinfectedwithSARS-CoV-2andthosewithcan cer on different fronts. Patients with cancer have been impacted by deferral, modification, and even cessation of therapy. Adaptive measures to minimize hospital exposure, following the precau tionary principle, have been proposed for cancer care during COVID-19 era. We present here a consensus on prioritizing rec ommendations across the continuum of sarcoma patient care. Material and Methods. A total of 125 recommendations were proposed in soft-tissue, bone, and visceral sarcoma care. Recom mendations were assigned as higher or lower priority if they can not or can be postponed at least 2–3 months, respectively. The consensus level for each recommendation was classified as “strongly recommended” (SR) if more than 90% of experts agreed, “recommended” (R) if75%–90% of experts agreed and “no consensus” (NC) if fewer than 75% agreed. Sarcoma experts from 11 countries within the Sarcoma European-Latin American Network (SELNET) consortium participated, including countries in the Americas and Europe. The European Society for Medical Oncology-Magnitude of clinical benefit scale was applied to systemic-treatment recommendations to support prioritization. Results. There were 80 SRs, 35 Rs, and 10 NCs among the 125 recommendations issued and completed by 31 multi e1563 disciplinary sarcoma experts. The consensus was higher among the 75 higher-priority recommendations (85%, 12%, and3%forSR,R,andNC, respectively)thaninthe50lower priority recommendations (32%, 52%, and 16% for SR, R, and NC, respectively). Conclusion. The consensus on 115 of 125 recommendations indicates a high-level of convergence among experts. The SELNET consensus provides a tool for sarcoma multi disciplinary treatment committees during the COVID-19 outbreak.
Sarcoma sinovial bifásico pulmonar. Presentación de un caso y revisión de la literatura
(2011-09) Torres Gómez, Francisco Javier; Vázquez Ramírez, Francisco José; Torres Olivera, Francisco Javier; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica
El sarcoma sinovial es una neoplasia agresiva que aun habiendo sido descrita en múltiples localizaciones, resulta sumamente infrecuente en localización pulmonar. Método: Presentamos un caso de sarcoma sinovial bifásico de localización pulmonar haciendo hincapié en sus características histológicas inmunohistoquímicas y genéticas así como en su diagnóstico diferencial. Resultados: La neoplasia mostraba un patrón bifásico bien caracterizado. El estudio genético demostró la translocación SYT-SSX. Comentarios: Si bien la histología y la inmunohistoquímica permiten en la mayoría de los casos el diagnóstico del sarcoma sinovial, es la translocación genética la que define verdaderamente esta entidad.
Integrating digital pathology with transcriptomic and epigenomic tools for predicting metastatic uterine tumor aggressiveness
(Frontiers Media SA, 2022-11-18) Sonzini, Giorgia; Granados-Aparici, Sofia; Sanegre, Sabina; Díaz-Lagares, Ángel; Díaz-Martín, Juan; Andrea, Carlos de; Salguero Aranda, Carmen; Álava Casado, Enrique de; Noguera, Rosa; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
The incidence of new cancer cases is expected to increase significantly in the future, posing a worldwide problem. In this regard, precision oncology and its diagnostic tools are essential for developing personalized cancer treatments. Digital pathology (DP) is a particularly key strategy to study the interactions of tumor cells and the tumor microenvironment (TME), which play a crucial role in tumor initiation, progression and metastasis. The purpose of this study was to integrate data on the digital patterns of reticulin fiber scaffolding and the immune cell infiltrate, transcriptomic and epigenetic profiles in aggressive uterine adenocarcinoma (uADC), uterine leiomyosarcoma (uLMS) and their respective lung metastases, with the aim of obtaining key TME biomarkers that can help improve metastatic prediction and shed light on potential therapeutic targets. Automatized algorithms were used to analyze reticulin fiber architecture and immune infiltration in colocalized regions of interest (ROIs) of 133 invasive tumor front (ITF), 89 tumor niches and 70 target tissues in a total of six paired samples of uADC and nine of uLMS. Microdissected tissue from the ITF was employed for transcriptomic and epigenetic studies in primary and metastatic tumors. Reticulin fiber scaffolding was characterized by a large and loose reticular fiber network in uADC, while dense bundles were found in uLMS. Notably, more similarities between reticulin fibers were observed in paired uLMS then paired uADCs. Transcriptomic and multiplex immunofluorescence-based immune profiling showed a higher abundance of T and B cells in primary tumor and in metastatic uADC than uLMS. Moreover, the epigenetic signature of paired samples in uADCs showed more differences than paired samples in uLMS. Some epigenetic variation was also found between the ITF of metastatic uADC and uLMS. Altogether, our data suggest a correlation between morphological and molecular changes at the ITF and the degree of aggressiveness. The use of DP tools for characterizing reticulin scaffolding and immune cell infiltration at the ITF in paired samples together with information provided by omics analyses in a large cohort will hopefully help validate novel biomarkers of tumor aggressiveness, develop new drugs and improve patient quality of life in a much more efficient way.
Cambios en la masa ósea en una población infantil con diabetes mellitus tipo 1. Estudio longitudinal
(Ibañez & Plaza Asoc., 2022) Vázquez Gámez, María de los Ángeles; Bocio-Núñez, Jesús; Bermúdez de la Vega, J. A.; Bernal Cerrato, S.; Giner García, Mercedes; Miranda García, M. J.; Hernández Cruz, B.; Olmo-Montes, J.; Barrera Barrera, J.; Montoya García, María José; Universidad de Sevilla. Departamento de Medicina; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS211: Metabolismo Cálcico, Hipertensión y Arteriosclerosis
Objetivo: Evaluar, a lo largo de un seguimiento de 79,2 meses, el comportamiento de la densidad mineral ósea (DMO) determinada mediante Densitometría Axial Computarizada (DXA), la densidad mineral ósea volumétrica (DMOvol) y su relación con los datos antropométricos, junto con los parámetros relativos al metabolismo óseo (calcio, fósforo, fosfatasa alcalina, parathormona (PTH) y vitamina D (25‐OH‐D3)) en una población infantil con Diabetes Mellitus Tipo 1 (DM1) sin complicaciones microvasculares y un grupo control de referencia de similares características. Material y métodos: Inicialmente, se realizó un estudio transversal en 40 niños diabéticos (edad media 9,4±2,8 años) y 108 controles (9,3±1,5 años) para valorar las posibles diferencias entre ambas poblaciones. 26 pacientes del grupo diabético inicial, fueron reevaluados tras 79,2 meses de seguimiento. Resultados: Se observó que, al inicio, la masa ósea fue similar en los diabéticos y controles. Después del seguimiento, la DMO de los niños diabéticos era muy inferior a la esperada en población infantil no diabética. El peso, la altura y el Índice de Masa Corporal (IMC) siguieron el mismo patrón que la DMO. Los valores de calcio, fósforo, fosfatasa alcalina, PTH y vitamina D, aunque en rango de normalidad, fueron más bajos que en los controles. La fosfatasa alcalina no se incrementó en el periodo puberal. Conclusiones: El presente estudio demuestra que los niños y adolescentes con un diagnóstico reciente de DM1 tienen una DMO normal. Sin embargo, con el paso del tiempo, y sobre todo durante la adolescencia, muestran una menor ga nancia de masa ósea y alteraciones en los parámetros de recambio óseo.
VE-Cadherin in cancer-associated angiogenesis: a deceptive strategy of blood vessel formation
(Mdpi Ag; Mdpi, 2023-05-26) Delgado-Bellido, Daniel; Oliver, F. J.; Vargas Padilla, María Victoria; Lobo Selma, Laura; Chacón-Barrado, Antonio; Díaz-Martin, Juan; Álava Casado, Enrique de; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Junta de Andalucía; Gobierno de España; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
Tumor growth depends on the vascular system, either through the expansion of blood vessels or novel adaptation by tumor cells. One of these novel pathways is vasculogenic mimicry (VM), which is defined as a tumor-provided vascular system apart from endothelial cell-lined vessels, and its origin is partly unknown. It involves highly aggressive tumor cells expressing endothelial cell markers that line the tumor irrigation. VM has been correlated with high tumor grade, cancer cell invasion, cancer cell metastasis, and reduced survival of cancer patients. In this review, we summarize the most relevant studies in the field of angiogenesis and cover the various aspects and functionality of aberrant angiogenesis by tumor cells. We also discuss the intracellular signaling mechanisms involved in the abnormal presence of VE-cadherin (CDH5) and its role in VM formation. Finally, we present the implications for the paradigm of tumor angiogenesis and how targeted therapy and individualized studies can be applied in scientific analysis and clinical settings.
Uterine sarcomas: clinical practice guidelines for diagnosis, treatment, and follow-up, by Spanish group for research on sarcomas (GEIS)
(Sage Publications Ltd, 2023) Pérez-Fidalgo, Jose Alejandro; Ortega, Eugenia; Ponce, Jordi; Redondo, Andrés; Sevilla, Isabel; Valverde, Claudia; Isern Verdum, Josep; Álava Casado, Enrique de; Galera López, Mar; Marquina, Gloria; Sebio, Ana; Universidad de Sevilla. Departamento de Citología e Histología Normal y Patológica; Universidad de Sevilla. CTS1035: Patología Molecular del Cáncer Sólido
Abstract: Uterine sarcomas are very infrequent and heterogeneous entities. Due to its rarity, pathological diagnosis, surgical management, and systemic treatment are challenging. Treatment decision process in these tumors should be taken in a multidisciplinary tumor board. Available evidence is low and, in many cases, based on case series or clinical trials in which these tumors have been included with other soft tissue sarcoma. In these guidelines, we have tried to summarize the most relevant evidence in the diagnosis, staging, pathological disparities, surgical management, systemic treatment, and follow-up of uterine sarcomas.

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