International single-step SNPBLUP beef cattle evaluations for Limousin weaning weight

Background Compared to national evaluations, international collaboration projects further improve accuracies of estimated breeding values (EBV) by building larger reference populations or performing a joint evaluation using data (or proxy of them) from different countries. Genomic selection is increasingly adopted in beef cattle, but, to date, the benefits of including genomic information in international evaluations have not been explored. Our objective was to develop an international beef cattle single-step genomic evaluation and investigate its impact on the accuracy and bias of genomic evaluations compared to current pedigree-based evaluations. Methods Weaning weight records were available for 331,593 animals from seven European countries. The pedigree included 519,740 animals. After imputation and quality control, 17,607 genotypes at a density of 57,899 single nucleotide polymorphisms (SNPs) from four countries were available. We implemented two international scenarios where countries were modelled as different correlated traits: an international genomic single-step SNP best linear unbiased prediction (SNPBLUP) evaluation (ssSNPBLUP(INT)) and an international pedigree-based BLUP evaluation (PBLUPINT). Two national scenarios were implemented for pedigree and genomic evaluations using only nationally submitted phenotypes and genotypes. Accuracies, level and dispersion bias of EBV of animals born from 2014 onwards, and increases in population accuracies were estimated using the linear regression method. Results On average across countries, 39 and 17% of sires and maternal-grand-sires with recorded (grand-)offspring across two countries were genotyped. ssSNPBLUP(INT) showed the highest accuracies of EBV and, compared to PBLUPINT, led to increases in population accuracy of 13.7% for direct EBV, and 25.8% for maternal EBV, on average across countries. Increases in population accuracies when moving from national scenarios to ssSNPBLUP(INT) were observed for all countries. Overall, ssSNPBLUP(INT) level and dispersion bias remained similar or slightly reduced compared to PBLUPINT and national scenarios. Conclusions International single-step SNPBLUP evaluations are feasible and lead to higher population accuracies for both large and small countries compared to current international pedigree-based evaluations and national evaluations. These results are likely related to the larger multi-country reference population and the inclusion of phenotypes from relatives recorded in other countries via single-step international evaluations. The proposed international single-step approach can be applied to other traits and breeds

Mise à jour 2014 des recommandations du GEFPICS pour l’évaluation du statut HER2 dans les cancers du sein en France

De nouvelles recommandations internationales pour l’évaluation du statut HER2 dans les cancers du sein, basées sur plus de dix ans d’expérience et sur les résultats d’études cliniques et de concordance entre les différentes techniques de détection, viennent tout juste de voir le jour. Le présent article a pour objet de faire le point sur ces nouvelles recommandations, à la lumière de la publication récente du groupe de travail de l’American Society of Clinical Oncology (ASCO) et du Collège des pathologistes américains (CAP), adaptées à la pratique de la pathologie en France et revues par le groupe GEFPICS. À l’ère de la médecine personnalisée, la détermination du statut HER2 reste un élément phare dans le panel des biomarqueurs théranostiques des cancers du sein. Si l’interprétation du statut HER2 dans les cancers du sein est aisée dans la majorité des cas, un certain nombre de situations anatomocliniques est d’interprétation plus délicate, telles que la possibilité rare mais réelle de l’hétérogénéité intra-tumorale du statut de HER2, les formes à différenciation micropapillaire ou la ré-évaluation du statut des biomarqueurs lors de la rechute métastatique. Ces nouvelles recommandations abordent ces différentes questions, reprécisent les conditions pré-analytiques optimales et les critères d’interprétation (notamment des cas 2+), afin de réduire au maximum le risque de faux négatifs. Plus que jamais, la mobilisation de la spécialité d’anatomo-cytopathologie autour de la qualité des tests théranostiques témoigne de son implication dans la chaîne des soins en cancérologie., Summary International guidelines on HER2 determination in breast cancer have just been updated by the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP), on the basis of more than ten-year practice, results of clinical trials and concordance studies. The GEFPICS group, composed of expert pathologists in breast cancer, herein presents these recommendations, adapted to the French routine practice. These guidelines highlight the possible diagnosis difficulties with regards to HER2 status determination, such as intra-tumor heterogeneity, special histological subtypes and biomarker re-evaluation during metastatic relapse. Pre-analytical issues and updated scoring criteria (especially for equivocal cases) are detailed, in order to decrease the occurrence of false negative cases. In the era of personalized medicine, pathologists are more than ever involved in the quality of oncotheranostic biomarker evaluation.

Recommandations du GEFPICS concernant la phase pré-analytique pour l’évaluation de HER2 et des récepteurs hormonaux dans le cancer du sein : mise à jour 2014

Les tumeurs fixées et incluses en paraffine sont quotidiennement utilisées pour l’évaluation des biomarqueurs nécessaires au traitement des patientes atteintes d’un cancer du sein invasif. Les nouvelles recommandations internationales sur la phase pré-analytique ont été récemment revues, confirmant l’importance de la prise en charge optimale des prélèvements pour garantir des tests d’immunohistochimie ou d’hybridation in situ de qualité, quel que soit le biomarqueur envisagé. Incluant les procédés de fixation et de préparation des tissus, toutes les procédures pré-analytiques doivent être validées, standardisées et tracées. Elles nécessitent la collaboration et la formation de toutes les personnes impliquées dans le circuit du prélèvement, du préleveur jusqu’au technicien de pathologie et au pathologiste en passant par l’infirmière, ou le coursier. La prise en charge initiale optimale des pièces et une fixation de qualité sont des étapes majeures à maîtriser dans la phase pré-analytique. Cette mise à jour des recommandations du groupe d’étude des facteurs pronostiques immunohistochimiques dans le cancer du sein (GEFPICS) détaille et commente les différentes étapes pré-analytiques. L’observation de ces règles de bonne pratique, l’utilisation rigoureuse de témoins internes et externes et la participation régulière à des programmes d’assurance qualité sont autant de garanties pour une évaluation correcte et pérenne des biomarqueurs oncothéranostiques., Summary Biomarker assessment of breast cancer tumor samples is part of the routine workflow of pathology laboratories. International guidelines have recently been updated, with special regards to the pre-analytical steps that are critical for the quality of immunohistochemical and in situ hybridization procedures, whatever the biomarker analyzed. Fixation and specimen handling protocols must be standardized, validated and carefully tracked. Cooperation and training of the personnel involved in the specimen workflow (e.g. radiologists, surgeons, nurses, technicians and pathologists) are of paramount importance. The GEFPICS’ update of the recommendations herein details and comments the different steps of the pre-analytical process. Application of these guidelines and participation to quality insurance programs are mandatory to ensure the correct evaluation of oncotheranostic biomarkers

International single-step SNPBLUP beef cattle evaluations for Limousin weaning weight

Background: Compared to national evaluations, international collaboration projects further improve accuracies of estimated breeding values (EBV) by building larger reference populations or performing a joint evaluation using data (or proxy of them) from different countries. Genomic selection is increasingly adopted in beef cattle, but, to date, the benefits of including genomic information in international evaluations have not been explored. Our objective was to develop an international beef cattle single-step genomic evaluation and investigate its impact on the accuracy and bias of genomic evaluations compared to current pedigree-based evaluations. Methods: Weaning weight records were available for 331,593 animals from seven European countries. The pedigree included 519,740 animals. After imputation and quality control, 17,607 genotypes at a density of 57,899 single nucleotide polymorphisms (SNPs) from four countries were available. We implemented two international scenarios where countries were modelled as different correlated traits: an international genomic single-step SNP best linear unbiased prediction (SNPBLUP) evaluation (ssSNPBLUPINT) and an international pedigree-based BLUP evaluation (PBLUPINT). Two national scenarios were implemented for pedigree and genomic evaluations using only nationally submitted phenotypes and genotypes. Accuracies, level and dispersion bias of EBV of animals born from 2014 onwards, and increases in population accuracies were estimated using the linear regression method. Results: On average across countries, 39 and 17% of sires and maternal-grand-sires with recorded (grand-)offspring across two countries were genotyped. ssSNPBLUPINT showed the highest accuracies of EBV and, compared to PBLUPINT, led to increases in population accuracy of 13.7% for direct EBV, and 25.8% for maternal EBV, on average across countries. Increases in population accuracies when moving from national scenarios to ssSNPBLUPINT were observed for all countries. Overall, ssSNPBLUPINT level and dispersion bias remained similar or slightly reduced compared to PBLUPINT and national scenarios. Conclusions: International single-step SNPBLUP evaluations are feasible and lead to higher population accuracies for both large and small countries compared to current international pedigree-based evaluations and national evaluations. These results are likely related to the larger multi-country reference population and the inclusion of phenotypes from relatives recorded in other countries via single-step international evaluations. The proposed international single-step approach can be applied to other traits and breeds