Détermination de facteurs moléculaires de chimiosensibilité dans les gliomes

Les gliomes sont les tumeurs primitives les plus fréquentes du système nerveux central, les plus graves et pour lesquelles la prise en charge thérapeutique doit être améliorée. L objectif de ce travail était de mettre en évidence des facteurs moléculaires de chimiosensibilité dans les gliomes. Nous avons montré qu en routine, le statut de l EGFR déterminé par immunohistochimie était suffisant en cas de forte expression de la protéine, ce qui évitait de recourir à la FISH et à la PCR. Par ailleurs, nous avons démontré que la présence d une amplification en FISH semblait procurer aux patients âgés de moins de 60 ans une survie plus courte. Dans une seconde étude, nous avons montré que le statut de méthylation de MGMT est un important facteur pronostique dans les glioblastomes récidivants traités par chirurgie et implantation in situ de BCNU ; qui permet de prédire l efficacité du traitement à la récidive. Cependant, le choix de la meilleure technique pour étudier le statut MGMT reste à définir.Gliomas are the most common and aggressive tumours of the central nervous system, and their therapeutical management need to be improved. The aim of this work was to determinate some molecular factors which where predictive of sensibility by chemotherapy. We showed that in the case of EGFR protein overexpression, PCR and FISH could be avoided in first intention because their positive predictive value for amplification is 97%. Furthermore, in multivariate analysis, there was a trend towards an association between shorter overall survival time and EGFR amplification as determined by FISH analysis in patients younger then 60 years. In a second study, we showed that MGMT methylation status is an important prognostic factor in recurrent GB treated with surgery plus BCNU wafers implantation and therefore is useful in predicting the outcome of GB therapy at recurrence. However, the best method to assess MGMT status needs to be determined.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Aspect anatomopathologique des organes foetaux après injection létale de chlorure de potassium

L'injection létale de chlorure de potassium (KCl) peut être un mode de suicide ou d'homicide. Les méthodes biologiques demeurant insuffisantes pour différencier le potassium endogène et exogène, la cause de la mort peut n'être que suspectée lors de la levée de corps. Nous proposons dans cette étude d'évaluer l'intérêt de l'anatomopathologie conventionnelle dans ce cadre. Nous avons choisi comme modèle les décès fœtaux secondaires à une interruption médicale de grossesse. Une étude cas (120) / témoins (244) prospective et rétrospective a été réalisée. Pour chaque cas, un examen macroscopique ainsi qu'une analyse histologique des viscères ont été effectués. Dans 6 cas, des dépôts macroscopiques blanchâtres sont observés. L'histologie retrouve dans 11 cas des cristaux lancéolés groupés en amas. Cette étude originale offre une application intéressante en médecine légale.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Découverte fortuite de micro-adénome endocrine pancréatique : à propos de deux cas

International audienceA 59-year-old male, was admitted to our hospital for a tumor of the pancreatic tail. Serum CEA and CA 19-9 levels were normal. Splenopancreasectomy found a desmoid tumour. A 69-year-old male was referred to our institution for chronic anemia and inflammatory syndrome with splenomegaly. Splenectomy showed an important splenic congestion and siderosis. Both patients had a type 2 diabetes mellitus. Furthermore, histological examination revealed pancreatic endocrine microadenomas. The two patients' postoperative course was unremarkable. Eleven and 24 months respectively after the diagnosis, the patients are alive and well, with no tumor recurrence.Un patient âgé de 59 ans a été hospitalisé pour prise en charge d’une tumeur de la queue du pancréas. Les taux sériques d’ACE et de CA 19-9 étaient normaux. La spléno-pancréatectomie caudale a révélé une tumeur desmoïde. Le second patient, âgé de 69 ans, a été hospitalisé pour prise en charge d’une anémie chronique inexpliquée associée à un syndrome inflammatoire et à une splénomégalie. La splénectomie a montré une importante congestion associée à une sidérose. L’examen histologique a conduit, dans ces deux observations de patients diabétiques de type 2, à la découverte fortuite de micro-adénomes endocrines pancréatiques. Les deux patients ne présentent pas de récidive respectivement à 11 et à 24 mois après l’intervention et bénéficient d’une simple surveillance clinique et radiologique

Age-at-death estimation based on the study of frontosphenoidal sutures

Determination of age at the time of death based on the observation of cranial sutures has led to numerous studies with sometimes contradictory results. The initial hypothesis being that suture closure is part of an age-related physiological process, the conflicting results have been interpreted by various authors as secondary to the choice of sutures, under the co-existing influence of pathological factors or genetic factors, or even independent of age. Despite these differences, macroscopic methods remain much used in anthropology and in forensic medicine. In our work, we evaluated the value of the degree of closure of the frontosphenoidal suture in estimating age at death of mature subjects, with the secondary objective of establishing a linear regression which could be used in routine practice. The study concerned bone specimens from individuals whose age, sex and medical history were known. Macroscopic observation was carried out on the ectocranial and endocranial sides according to four stages of closure previously defined. 290 sutures were taken from a population of whom two-thirds were men. The method can be repeated and reproduced and the regression established shows the confidence range for average error to be 1.5 years. While this result is of interest in terms of precision in prediction for a group of people, the prediction range is too great ( 23 years) to be applicable to a single individual as part of a forensic procedure

Epidermal growth factor receptor in glioblastomas: correlation between gene copy number and protein expression

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Epidermal growth factor receptor expression and KRAS and BRAF mutations: study of 39 sinonasal intestinal-type adenocarcinomas.

International audienceSinonasal intestinal-type adenocarcinomas (ITACs) are uncommon tumors of poor prognosis defined by their similarities to colorectal adenocarcinomas. The involvement of the epidermal growth factor receptor (EGFR) pathway in colorectal adenocarcinoma oncogenesis is well established, and the same is expected to apply to ITACs. In a series of 39 ITACs, we investigated EGFR amplification and chromosome 7 polysomy by fluorescence in situ hybridization; EGFR, KRAS, and BRAF mutational status by polymerase chain reaction sequencing; EGFR variant messenger RNA expression by quantitative reverse transcriptase polymerase chain reaction; and EGFR protein expression by immunohistochemistry with antibodies targeting the extracellular domain, the intracellular domain, and the phosphorylated isoform. The findings were analyzed with respect to clinical data, histologic typing, and patient outcome. EGFR amplification was observed in 3 cases with a focal distribution. EGFR proteins were overexpressed in all these foci with both extracellular domain and intracellular domain antibodies, suggesting involvement of the whole receptor. Chromosome 7 polysomy was observed in 15 cases and was not associated with EGFR protein expression. EGFR, KRAS, or BRAF mutations were observed in 5 different cases. The EGFRvIII mutant was not detected. In all cases, EGFR variants were expressed. There was no association between these molecular features and patient survival. In conclusion, (1) our study revealed various EGFR expression patterns in ITACs, indicating tumor heterogeneity; (2) EGFR amplification should be distinguished from chromosome 7 polysomy; (3) fluorescence in situ hybridization analysis could be guided by immunohistochemistry; and (4) ITACs share common alterations of the EGFR pathway with colorectal adenocarcinomas, except for a lower frequency of KRAS and BRAF mutations

Prognostic Impact of CD133 mRNA Expression in 48 Glioblastoma Patients Treated with Concomitant Radiochemotherapy: A Prospective Patient Cohort at a Single Institution

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Prognostic impact of O 6 -methylguanine-DNA methyltransferase silencing in patients with recurrent glioblastoma multiforme who undergo surgery and carmustine wafer implantation

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