The Use of P63 Immunohistochemistry for the Identification of Squamous Cell Carcinoma of the Lung

6 páginas, 2 figuras, 3 tablas.Introduction While some targeted agents should not be used in squamous cell carcinomas (SCCs), other agents might preferably target SCCs. In a previous microarray study, one of the top differentially expressed genes between adenocarcinomas (ACs) and SCCs is P63. It is a well-known marker of squamous differentiation, but surprisingly, its expression is not widely used for this purpose. Our goals in this study were (1) to further confirm our microarray data, (2) to analize the value of P63 immunohistochemistry (IHC) in reducing the number of large cell carcinoma (LCC) diagnoses in surgical specimens, and (3) to investigate the potential of P63 IHC to minimize the proportion of “carcinoma NOS (not otherwise specified)” in a prospective series of small tumor samples. Methods With these goals in mind, we studied (1) a tissue-microarray comprising 33 ACs and 99 SCCs on which we performed P63 IHC, (2) a series of 20 surgically resected LCCs studied for P63 and TTF-1 IHC, and (3) a prospective cohort of 66 small thoracic samples, including 32 carcinoma NOS, that were further classified by the result of P63 and TTF-1 IHC. Results The results in the three independent cohorts were as follows: (1) P63 IHC was differentially expressed in SCCs when compared to ACs (p<0.0001); (2) half of the 20 (50%) LCCs were positive for P63 and were reclassified as SCCs; and (3) all P63 positive cases (34%) were diagnosed as SCCs. Conclusions P63 IHC is useful for the identification of lung SCCs.This work was partially funded by grants from Fundacion Mutua Madrileña to EC, FLR, and LPA; CIBER Respiratory Disease to ALE (ISCIII-CB06/06); and Red Temática de Investigacion Cooperativa en Cancer (RTICC) to MSC (RD06/0020/0062). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Accurate Identification of ALK Positive Lung Carcinoma Patients: Novel FDA-Cleared Automated Fluorescence In Situ Hybridization Scanning System and Ultrasensitive Immunohistochemistry

Background: Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples. Methods: Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system. Results: All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively. Conclusions: The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situation

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe

Search for anomalous couplings in boosted WW/WZ -> l nu q(q)over-bar production in proton-proton collisions at root s=8TeV

Peer reviewe

Clericalismo, versión latinoamericana: sus especificidades y peligros : los casos de Perú y Argentina

Resume: Les recherches développées dans l’hémisphère Nord sur les abus de pouvoir, de conscience et sexuels dans l’Église concluent que le cléricalisme, en tant que perversion de l’exercice de l’autorité, est le principal responsable de la crise actuelle, conclusion reprise et fréquemment commentée par le pape François. Pour les auteurs, le phénomène ne correspond pas à des faiblesses individuelles mais à une organisation institutionnelle le favorisant. Certaines composantes du cléricalisme sont universelles, conséquences des structures uniformes de l’Église, en revanche, d’autres caractéristiques correspondent à l’organisation sociale et culturelle locale. Á partir d›une étude en Argentine et au Pérou, résultat d›un projet de recherche financé par le Intercambio Cultural Alemán-Latinoamericano, Icala, et d’antérieurs projets, cet article se propose de combler un manque en analysant le cléricalisme et son impact dans la crise des abus, en contexte latino-américain. Les composantes universelles du phénomène se renforcent et acquièrent de nouvelles caractéristiques en Amérique Latine. Les multiples facettes du cléricalisme se rejoignent toutes autour d’un noyau commun, l’exercice sans contrepoids du pouvoir. Plusieurs facteurs, tels que le prestige de l’Église, la faiblesse des institutions gouvernementales, l’usage discrétionnaire de ressources, le machisme, les tendances culturelles à l’autoritarisme et l’européisation des formations en séminaires, transforment les prêtres en êtres d’exception et exacerbent leur pouvoir de type monarchique sur des laïcs passifs sans capacité, ni volonté de fiscalisation (Schickendantz). Par ailleurs, l’aura de sacré que tend à conférer le sacrement de l’ordre, en général, acquiert de nouvelles dimensions en contexte de modernité enchantée latino-américaine. Par leurs bénédictions, les prêtres sacralisent et purifient tous les objets du quotidien, les transformant en source de bien-être. Les changements actuels dans les pratiques de dévotions populaires renforcent ces tendances, faisant des prêtres des fournisseurs de bénédictions à volonté. Pour rompre les multiples renforcements qui justifient ce style de gouvernance, il faudrait développer dans l’Église une culture de la vulnérabilité (Keenan): envisager le prêtre non seulement comme un clerc au service des laïcs mais aussi comme un homme qui a besoin des laïcs pour être vraiment prêtre.Resumen: La investigación desarrollada en el hemisferio Norte sobre el abuso de poder, conciencia y sexualidad en la Iglesia concluye que el clericalismo, como una perversión del ejercicio de la autoridad, es el principal responsable de la crisis actual, conclusión repetida y frecuentemente comentada por el papa Francisco. Para las autoras, el fenómeno no corresponde a debilidades individuales sino a una organización institucional que lo favorece. Ciertos componentes del clericalismo son universales, consecuencia de las estructuras uniformes de la Iglesia, por otro lado, otras características corresponden a la organización social y cultural local. Basado en un estudio en Argentina y Perú, resultado de un proyecto de investigación financiado por el Intercambio Cultural Alemán-Latinoamericano, Icala, y proyectos anteriores, este artículo propone llenar un vacío analizando el clericalismo y su impacto en la crisis del abuso, desde el contexto latinoamericano. Los componentes universales del fenómeno se están fortaleciendo y adquiriendo nuevas características en América Latina. Las múltiples facetas del clericalismo se unen en torno a un núcleo común, el ejercicio desequilibrado del poder. Varios factores, como el prestigio de la Iglesia, la debilidad de las instituciones gubernamentales, el uso discrecional de los recursos, el machismo, las tendencias culturales hacia el autoritarismo y la europeización de las formaciones seminaristas, transforman a los sacerdotes en seres de excepción y exacerban su poder de tipo monárquico sobre laicos pasivos, sin capacidad ni voluntad para fiscalizar (Schickendantz). Además, el aura de sagrado que tiende a conferir el sacramento del orden, en general, adquiere nuevas dimensiones en el contexto de la modernidad encantada latinoamericana (Morello et al.). Con sus bendiciones, los sacerdotes santifican y purifican todos los objetos cotidianos, transformándolos en una fuente de bienestar. Los cambios actuales en las prácticas devocionales populares refuerzan estas tendencias, convirtiendo a los sacerdotes en proveedores de bendiciones a voluntad. Para romper los múltiples refuerzos que justifican este estilo de gobierno, sería necesario desarrollar en la Iglesia una cultura de la vulnerabilidad (Keenan): considerar al sacerdote no solo como un clérigo al servicio de los laicos, sino también como un hombre que necesita a los laicos para ser verdaderamente un sacerdote

PD-L1 testing based on the SP142 antibody in metastatic triple-negative breast cancer: summary of an expert round-table discussion

Triple-negative breast cancer (TNBC) is more aggressive than other breast cancer subtypes. TNBC is characterized by increased expression of Programmed Death-ligand 1 (PD-L1), a signal used by many tumors to escape the immune response. Expression of PD-L1 is a positive predictor of response to immunotherapy; therefore, it should be investigated in TNBC in order to select patients who may benefit from anti-PD-L1 therapies. While many PD-L1 assays are available, only the VENTANA platform with the anti-PD-L1 (SP142) antibody is licensed as a companion diagnostic device for selecting patients with metastatic/advanced TNBC who are candidates for treatment with atezolizumab. In this article, we provide a summary of an expert round-table discussion about PD-L1 testing, using the SP142 antibody in metastatic TNBC

A comparison of EGFR mutation testing methods in lung carcinoma: direct sequencing, real-time PCR and immunohistochemistry.

The objective of this study is to compare two EGFR testing methodologies (a commercial real-time PCR kit and a specific EGFR mutant immunohistochemistry), with direct sequencing and to investigate the limit of detection (LOD) of both PCR-based methods. We identified EGFR mutations in 21 (16%) of the 136 tumours analyzed by direct sequencing. Interestingly, the Therascreen EGFR Mutation Test kit was able to characterize as wild-type one tumour that could not be analyzed by direct sequencing of the PCR product. We then compared the LOD of the kit and that of direct sequencing using the available mutant tumours. The kit was able to detect the presence of a mutation in a 1% dilution of the total DNA in nine of the 18 tumours (50%), which tested positive with the real-time quantitative PCR method. In all cases, EGFR mutation was identified at a dilution of 5%. Where the mutant DNA represented 30% of the total DNA, sequencing was able to detect mutations in 12 out of 19 cases (63%). Additional experiments with genetically defined standards (EGFR ΔE746-A750/+ and EGFR L858R/+) yielded similar results. Immunohistochemistry (IHC) staining with exon 19-specific antibody was seen in eight out of nine cases with E746-A750del detected by direct sequencing. Neither of the two tumours with complex deletions were positive. Of the five L858R-mutated tumours detected by the PCR methods, only two were positive for the exon 21-specific antibody. The specificity was 100% for both antibodies. The LOD of the real-time PCR method was lower than that of direct sequencing. The mutation specific IHC produced excellent specificity