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Prolifération et signatures ADN de complexité génomique pour la définition du pronostic des carcinomes mammaires

Proliferation and genome complexity-based signature for prognostic determination of invasive breast carcinomas

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Oncologie

Abstract

Invasive breast carcinoma’s prognosis is defined using clinico-pathological parameters among which proliferation is essential. Ki67 has strong prognostic and predictive values. Ki67 is expressed during all the cell cycle but G0. The determination of its expression with the MIB1 antibody, on tissue sections, requires well-controlled preanalytical steps for tissue preparation (fixation and paraffinembedding) and an accurate protocol for immunohistochemistry. These technical issues are limiting but largely balanced with immunohistochemistry’s low cost and its wide utilization in pathology laboratories. Ki67 staining’s interpretation follows international guidelines recently published without any recommended cut-off. However, the most commonly used is 20% of stained cells. Genome complexity assessed with DNA arrays provides another level of prognostic information. The higher the number of chromosome breakpoints, the poorer the prognosis. However, until now, this tool remains useful in the context of clinical trials in specialized centers.

Résumé

La définition du pronostic des carcinomes mammaires infiltrants à l’aide des paramètres cliniques et pathologiques classiques s’appuie sur la mesure de la prolifération. L’expression du Ki67 est observée pendant tout le cycle cellulaire hormis la phase G0. Son analyse immunohistochimique sur coupe tissulaire des carcinomes mammaires requiert la maîtrise des conditions de fixation et de préparation des biopsies et pièces opératoires ainsi que des protocoles de marquages. Son interprétation doit suivre les recommandations internationales récemment publiées. Le seuil communément admis pour distinguer les tumeurs proliférant faiblement de celles proliférant fortement est de 20 % de cellules positives. Ces différents aspects représentent les principales limites de son utilisation. Cependant, sa mise en oeuvre aisée dans les laboratoires de pathologie, son faible coût, sa robustesse face aux effets de la fixation tissulaire ainsi que ses pouvoirs pronostique et prédictif forts en font un outil clé de la prise en charge thérapeutique des carcinomes mammaires. Cette prise en charge peut être encore affinée par l’utilisation d’informations moléculaires issues des données des puces analysant les anomalies de nombres et de structures des chromosomes (comme l’hybridation génomique comparative ou les SNP 6.0 Affymetrix ®). En effet, plus le nombre de cassures chromosomiques augmente, moins le pronostic est bon. Mais ces technologies sont l’apanage de centres spécialisés et ne peuvent à l’heure actuelle être utilisées que dans le cadre d’essais thérapeutiques.

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  1. Département de pathologie et Inserm U830, institut Curie, 26, rue d’Ulm, F-75248, Paris cedex 05, France

    A. Vincent-Salomon

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Vincent-Salomon, A. Prolifération et signatures ADN de complexité génomique pour la définition du pronostic des carcinomes mammaires. Oncologie 14, 502–505 (2012). https://doi.org/10.1007/s10269-012-2201-6

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  • DOI: https://doi.org/10.1007/s10269-012-2201-6

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