Atlas de correlación anatomía patológica y radiología. Experiencia en la Universidad de Málaga

Introducción: Con la introducción del Grado en la facultad de medicina de Málaga, se ha hecho necesaria la introducción de nuevas técnicas y herramientas docentes que ayuden al alumno a la mejora de su formación a través de la realización de horas prácticas. La integración de conocimientos ayuda al estudiante de medicina a tener una mejor formación. De lo expuesto nace la idea de crear una herramienta que permita integrar la enseñanza impartida en las asignaturas de Radiología y Anatomía Patológica. Ambas tienen como nexo en común su trascendencia en el diagnóstico de enfermedades basándose en el análisis de imágenes y estructuras que, en todo caso, se encuentran íntimamente relacionadas y además son complementarias en el diagnóstico. Material y método: El proyecto comenzó a realizarse durante el curso 2013-14. Consiste en una colección de casos que se presentan en la pantalla del ordenador secuencialmente, con el objeto de ofrecer al alumno un primer contacto con imágenes anatomopatológicas y su correlación con imágenes radiológicas y así proporcionar entrenamiento visual, tanto para distinguir las diferentes piezas anatomopatológicas,( micro y macroscópicas) como distintas modalidades de exploraciones radiológicas, No pretende ser una lección exhaustiva de anatomía patológica ni de radiología, sino una herramienta práctica para entrenar la percepción visual del usuario. ¿Cómo? Mostrando un número suficientemente amplio de casos para que el usuario vaya entrenándose a lo que tendrá que realizar en su formación médica. Resultados: Se han recogido 20 casos clínicos distintos (tumores de mama, colon, hueso, vejiga…) con sus respectivas imágenes anatomopatológicas y radiológicas. El formato de presentación de esta actividad es tipo atlas, en power-point, accesible a través del Campus Virtual. Lleva asociado un cuestionario de autoevaluación para que el alumno conozca el nivel de aprendizaje alcanzado y los conocimientos y habilidades que debe perfeccionar. El control y la evaluación de la actividad se llevarán a cabo mediante la valoración de los resultados de los alumnos y cuestionarios y encuestas realizadas antes y después de su realización. Conclusión: Se ha realizado una herramienta que permite no sólo al alumno de grado, sino también al médico en formación, facilitar su aprendizaje en especialidades distintas como son la anatomía patológica y el radiodiagnóstico, pero complementarias en el diagnóstico de patologías.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Targeted therapies in the treatment of germ cell tumors: The need for new approaches against “orphan” tumors

Este artículo ha sido publicado en la revista Critical Reviews in Oncology/Hematology Esta versión tiene Licencia Creative Commons CC-BY-NC-NDGerm cell tumors (GCTs) are a heterogeneous group of tumors that are highly clinically relevant to oncologists. GCTs are generally highly sensitive to cisplatin-based chemotherapy and represent a model for curable neoplasms. Cisplatin-based combination therapy followed by surgical resection of the residual tumor is the cornerstone for GCTs treatment. Although the overall cure rate is high for patients with GCTs, patients with a poor prognosis according to International Consensus Criteria or with chemoresistant disease remain a major clinical challenge. Currently, between 15% and 20% of patients with metastatic disease still progress and will die as a consequence of the disease. Therefore, the discovery of new treatment strategies or new drugs based on translational oncology remains a priority for the treatment of patients with cisplatin-refractory disease and those with a poor prognosis. Clinical trials with new targeted therapies are ongoing for the treatment of GCTs. In this article, we review some of the new targeted biologic therapies that act on the most relevant oncogenesis pathways and are in clinical development for the treatment of GCT

Estudio sobre la vegetación y la flora forestal de la provincia de Málaga

En portada: Trabajo que se publica como complemento al mapa forestal de la misma.Indices.Copia digital : Diputación de Málaga. Biblioteca Canovas del Castillo, 201

Nationwide trends of invasive pneumococcal disease in Spain (2009-2019) in children and adults during the pneumococcal conjugate vaccine era.

Introduction of pneumococcal conjugate vaccines (PCVs) has shown a marked reduction in the disease caused by vaccine serotypes in children providing herd protection to the elderly group. However, the emergence of non-vaccine serotypes is of great concern worldwide. This study includes national laboratory data from invasive pneumococcal disease (IPD) cases affecting pediatric and adult population during 2009-2019. The impact of implementing different vaccine strategies for immunocompetent adults comparing Spanish regions using PCV13 vs regions using PPV23 vaccine was also analyzed for 2017-2019. The overall reductions of IPD cases by PCV13 serotypes in children and adults were 88% and 59% respectively during 2009-2019 with a constant increase of serotype 8 in adults since 2015. IPD cases by additional serotypes covered by PPV23 increased from 20% in 2009 to 52% in 2019. In children, serotype 24F was the most frequent in 2019 whereas in adults, serotypes 3 and 8 accounted for 36% of IPD cases. Introduction of PCV13 or PPV23 in the adult calendar of certain Spanish regions reduced up to 25% and 11% respectively the IPD cases by PCV13 serotypes, showing a decrease of serotype 3 when PCV13 was used. Use of PCV13 in children has shown a clear impact in pneumococcal epidemiology reducing the burden of IPD in children but also in adults by herd protection although the increase of serotype 8 in adults is worrisome. Vaccination with PCV13 in immunocompetent adults seems to control IPD cases by PCV13 serotypes including serotype 3.This work was supported by Ministerio de Economía, Industria y Competitividad (MINECO) [grant SAF2017-83388] and internal funding fromS

Subtipado molecular del cáncer de mama masculino con PAM50: Correlación con el subtipaje inmunohistoquímico y estudio de supervivencia.

Introducción: El cáncer de mama masculino es una enfermedad rara aún poco conocida, que principalmente corresponde a subtipo luminal usando la clasificación molecular subrogada a inmunohistoquímica. En este estudio, se evalúa por primera vez la correlación entre los subtipos moleculares basados en un panel inmunohistoquímico de seis marcadores y el obtenido mediante la firma PAM50 en el cáncer de mama masculino, así como la evolución clínica de los diferentes subtipos encontrados. Material y métodos: Se recogieron 67 muestras quirúrgicas de cáncer de mama masculino invasivo de cuatro diferentes Servicios de Anatomía Patológica. La tinción inmunohistoquímica se realizó sobre tissue-microarrays, con un panel de seis marcadores (RE, RP, Her2, Ki67, CK 5-6 y EGFR). Los subtipos de PAM50 se determinaron mediante nCounter Analysis System. Se estudió la asociación entre los subtipos obtenidos mediante inmunohistoquímica y los determinados por PAM50, así como la supervivencia global y la supervivencia libre de enfermedad en los diferentes subtipos de cada clasificación. Resultados: La distribución de los subtipos moleculares tumorales según PAM50 fue: 60% luminal B, 30% luminal A y 10% Her2-enriched. Sólo uno de los tumores Her2-enriched también fue detectado por inmunohistoquímica y tratado con trastuzumab. No se obtuvo ningún tumor de subtipo basal-like. Utilizando la clasificación inmunohistoquímica, 51% de los tumores fueron luminal B, 43% luminal A, 3,5% triple negativo y 1,5% Her2-positivo. Las características clínico-patológicas no difirieron significativamente entre los subtipos inmunohistoquímicos y PAM50. Se observó una supervivencia global menor en los tumores Her2-enriched comparados con los luminales. Conclusión: El cáncer de mama masculino es principalmente una enfermedad genómica luminal con un predominio del subtipo luminal B. Además, se observaron casos de pacientes Her2-negativos por inmunohistoquímica, pero de perfil Her2-enriched por PAM50, con peor evolución clínica comparado con el subtipo luminal, que podrían haberse beneficiado de terapia anti-Her2.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Male breast cancer: correlation between immunohistochemical subtyping and PAM50 intrinsic subtypes, and the subsequent clinical outcomes

Política de acceso abierto tomada de: https://beta.sherpa.ac.uk/id/publication/4003Male breast cancer is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry as a luminal disease. In this study, we assess for the first time the correlation between molecular subtypes based on a validated six-marker immunohistochemical panel and PAM50 signature in male breast cancer, and the subsequent clinical outcome of these different subtypes. We collected 67 surgical specimens of invasive male breast cancer from four different Spanish pathology laboratories. Immunohistochemical staining for the six-marker panel was performed on tissue microarrays. PAM50 subtypes were determined in a research-use-only nCounter Analysis System. We explored the association of immunohistochemical and PAM50 subtypes. Overall survival and disease-free survival were analyzed in the different subtypes of each classification. The distribution of tumor molecular subtypes according PAM50 was: 60% luminal B, 30% luminal A and 10% human epidermal growth factor receptor 2 (Her2) enriched. Only one Her2-enriched tumor was also positive by immunohistochemistry and was treated with trastuzumab. None of the tumors were basal-like. Using immunohistochemical surrogates, 51% of the tumors were luminal B, 44% luminal A, 4% triple-negative and 1% Her2-positive. The clinicopathological characteristics did not differ significantly between immunohistochemical and PAM50 subtypes. We found a significant worse overall survival in Her2-enriched compared with luminal tumors. Male breast cancer seems to be mainly a genomic luminal disease with a predominance of the luminal B subtype. In addition, we found a proportion of patients with Her2-negative by immunohistochemistry but Her2-enriched profile by PAM50 tumors with a worse outcome compared with luminal subtypes that may benefit from anti-Her2 therapies

Male breast cancer: correlation between immunohistochemical subtyping and PAM50 intrinsic subtypes, and the subsequent clinical outcomes.

Male breast cancer is a rare disease that is still poorly understood. It is mainly classified by immunohistochemistry as a luminal disease. In this study, we assess for the first time the correlation between molecular subtypes based on a validated six-marker immunohistochemical panel and PAM50 signature in male breast cancer, and the subsequent clinical outcome of these different subtypes. We collected 67 surgical specimens of invasive male breast cancer from four different Spanish pathology laboratories. Immunohistochemical staining for the six-marker panel was performed on tissue microarrays. PAM50 subtypes were determined in a research-use-only nCounter Analysis System. We explored the association of immunohistochemical and PAM50 subtypes. Overall survival and disease-free survival were analyzed in the different subtypes of each classification. The distribution of tumor molecular subtypes according PAM50 was: 60% luminal B, 30% luminal A and 10% human epidermal growth factor receptor 2 (Her2) enriched. Only one Her2-enriched tumor was also positive by immunohistochemistry and was treated with trastuzumab. None of the tumors were basal-like. Using immunohistochemical surrogates, 51% of the tumors were luminal B, 44% luminal A, 4% triple-negative and 1% Her2-positive. The clinicopathological characteristics did not differ significantly between immunohistochemical and PAM50 subtypes. We found a significant worse overall survival in Her2-enriched compared with luminal tumors. Male breast cancer seems to be mainly a genomic luminal disease with a predominance of the luminal B subtype. In addition, we found a proportion of patients with Her2-negative by immunohistochemistry but Her2-enriched profile by PAM50 tumors with a worse outcome compared with luminal subtypes that may benefit from anti-Her2 therapies.We gratefully acknowledge Nanostring Technologies team for providing the reagents for PAM50 subtypes determination as well as technical support, Maria José Lozano for her support with samples immunostaining and Jose M Roldan for the edition of the artwork. Angela Santonja has a predoctoral grant PFIS-ISCIII (FI12/00489)

Gene expression analyses determine two different subpopulations in KIT-negative GIST-like (KNGL) patients

Introduction: there are limited findings available on KIT-negative GIST-like (KNGL) population. Also, KIT expression may be post-transcriptionally regulated by miRNA221 and miRNA222. Hence, the aim of this study is to characterize KNGL population, by differential gene expression, and to analyze miRNA221/222 expression and their prognostic value in KNGL patients. Methods: KIT, PDGFRA, DOG1, IGF1R, MIR221 and MIR222 expression levels were determined by qRT-PCR. We also analyzed KIT and PDGFRA mutations, DOG1 expression, by immunohistochemistry, along with clinical and pathological data. Disease-free survival (DFS) and overall survival (OS) differences were calculated using Log-rank test. Results: hierarchical cluster analyses from gene expression data identified two groups: group I had KIT, DOG1 and PDGFRA overexpression and IGF1R underexpression and group II had overexpression of IGF1R and low expression of KIT, DOG1 and PDGFRA. Group II had a significant worse OS (p = 0.013) in all the series, and showed a tendency for worse OS (p = 0.11), when analyzed only the localized cases. MiRNA222 expression was significantly lower in a control subset of KIT-positive GIST (p < 0.001). OS was significantly worse in KNGL cases with higher expression of MIR221 (p = 0.028) or MIR222 (p = 0.014). Conclusions: we identified two distinct KNGL subsets, with a different prognostic value. Increased levels of miRNA221/222, which are associated with worse OS, could explain the absence of KIT protein expression of most KNGL tumors

Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy.

Este articulo ha sido publicado en la revista Oncotarget. Esta versión tiene Licencia Creative Commons CC-BYTriple negative breast cancer (TNBC) is a heterogeneous disease with distinct molecular subtypes that differentially respond to chemotherapy and targeted agents. The purpose of this study is to explore the clinical relevance of Lehmann TNBC subtypes by identifying any differences in response to neoadjuvant chemotherapy among them. We determined Lehmann subtypes by gene expression profiling in paraffined pre-treatment tumor biopsies from 125 TNBC patients treated with neoadjuvant anthracyclines and/or taxanes +/- carboplatin. We explored the clinicopathological characteristics of Lehmann subtypes and their association with the pathologic complete response (pCR) to different treatments. The global pCR rate was 37%, and it was unevenly distributed within Lehmann’s subtypes. Basal-like 1 (BL1) tumors exhibited the highest pCR to carboplatin containing regimens (80% vs 23%, p=0.027) and were the most proliferative (Ki-67>50% of 88.2% vs. 63.7%, p=0.02). Luminal-androgen receptor (LAR) patients achieved the lowest pCR to all treatments (14.3% vs 42.7%, p=0.045 when excluding mesenchymal stem-like (MSL) samples) and were the group with the lowest proliferation (Ki-67≤50% of 71% vs 27%, p=0.002). In our cohort, only tumors with LAR phenotype presented non-basal-like intrinsic subtypes (HER2- enriched and luminal A). TNBC patients present tumors with a high genetic diversity ranging from highly proliferative tumors, likely responsive to platinum-based therapies, to a subset of chemoresistant tumors with low proliferation and luminal characteristics.This work was supported by Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) from Instituto de Salud Carlos III (ISCIII) (CB16/12/00241, CB16/12/00471, CB16/12/00481) and by research grants from ISCIII (PI13/00730), Mutua Madrileña 2013 and Sociedad Española de Oncología Médica (SEOM) 2013. The authors acknowledge support through grant TIN2017- 88728-C2-1-R from MICINN-SPAIN. Angela Santonja has a predoctoral grant PFIS-ISCIII (FI12/00489)

Development of a Novel NGS Methodology for Ultrasensitive Circulating Tumor DNA Detection as a Tool for Early-Stage Breast Cancer Diagnosis

Breast cancer (BC) is the most prevalent cancer in women. While usually detected when localized, invasive procedures are still required for diagnosis. Herein, we developed a novel ultrasensitive pipeline to detect circulating tumor DNA (ctDNA) in a series of 75 plasma samples from localized BC patients prior to any medical intervention. We first performed a tumor-informed analysis to correlate the mutations found in tumor tissue and plasma. Disregarding the tumor data next, we developed an approach to detect tumor mutations in plasma. We observed a mutation concordance between the tumor and plasma of 29.50% with a sensitivity down to 0.03% in mutant variant allele frequency (VAF). We detected mutations in 33.78% of the samples, identifying eight patients with plasma-only mutations. Altogether, we determined a specificity of 86.36% and a positive predictive value of 88.46% for BC detection. We demonstrated an association between higher ctDNA median VAF and higher tumor grade, multiple plasma mutations with a likelihood of relapse and more frequent TP53 plasma mutations in hormone receptor-negative tumors. Overall, we have developed a unique ultra-sensitive sequencing workflow with a technology not previously employed in early BC, paving the way for its application in BC screening.Comino-Mendez’s contract is funded by the Spanish Association Against Cancer Scientific Foundation (AECC). This study was supported by the “Consejería de Salud y Familias—Junta de Andalucía” (PI-0291-2019), “Fundación Unicaja” is funding Alba-Bernal’s contract and the Andalusia-Roche Network in Precision Medical Oncology Quirós-Ortega’s contract. Carbajosa-Antona’s contract is funded by the “Ayudas María Zambrano para la atracción de talento internacional—Universidad de Málaga”. Partial funding for open access charge: Universidad de Málag