Early detection of breast cancer based on gene-expression patterns in peripheral blood cells

INTRODUCTION: Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. In this study, we investigated whether early detection of breast cancer is possible by analyzing gene-expression patterns in peripheral blood cells. METHODS: Using macroarrays and nearest-shrunken-centroid method, we analyzed the expression pattern of 1,368 genes in peripheral blood cells of 24 women with breast cancer and 32 women with no signs of this disease. The results were validated using a standard leave-one-out cross-validation approach. RESULTS: We identified a set of 37 genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of these genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defense-related genes was increased in samples from breast cancer patients. CONCLUSION: The results show that a blood-based gene-expression test can be developed to detect breast cancer early in asymptomatic patients. Additional studies with a large sample size, from women both with and without the disease, are warranted to confirm or refute this finding

Protein expression, survival and docetaxel benefit in node-positive breast cancer treated with adjuvant chemotherapy in the FNCLCC - PACS 01 randomized trial

International audienceABSTRACT: INTRODUCTION: The PACS01 trial has demonstrated that docetaxel addition to adjuvant anthracycline-based chemotherapy improves disease-free survival (DFS) and overall survival of node-positive early breast cancer (EBC). We searched for prognostic and predictive markers for docetaxel benefit. METHODS: Tumor samples from 1.099 recruited women were analyzed for the expression of 34 selected proteins using immunohistochemistry. The prognostic and predictive values of each marker and four molecular subtypes (luminal A, luminal B, HER2-overexpressing, and triple-negative) were tested. RESULTS: Progesterone receptor-negativity (HR=0.66; 95%CI 0.47-0.92, P=0.013), and Ki67-positivity (HR=1.53; 95%CI 1.12-2.08, P=0.007) were independent adverse prognostic factors. Out of the 34 proteins, only Ki67-positivity was associated with DFS improvement with docetaxel addition (adjusted HR=0.51, 95%CI 0.33-0.79 for Ki67-positive versus HR=1.10, 95%CI 0.75-1.61 for Ki67-negative tumors, P for interaction=0.012). Molecular subtyping predicted the docetaxel benefit, but without providing additional information to Ki67 status. The luminal A subtype did not benefit from docetaxel (HR=1.16, 95%CI 0.73-1.84); the reduction in the relapse risk was 53% (HR=0.47, 95%CI 0.22-1.01), 34% (HR=0.66, 95%CI 0.37-1.19), and 12% (HR=0.88, 95%CI 0.49-1.57) in the luminal B, HER2-overexpressing, and triple-negative subtypes, respectively. CONCLUSIONS: In patients with node-positive EBC receiving adjuvant anthracycline-based chemotherapy, the most powerful predictor of docetaxel benefit is Ki67-positivity

CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines.

INTRODUCTION: Metastasis is a complex process involving loss of adhesion, migration, invasion and proliferation of cancer cells. Cell adhesion molecules play a pivotal role in this phenomenon by regulating cell-cell and cell-matrix interactions. CD146 (MCAM) is associated with an advanced tumor stage in melanoma, prostate cancer and ovarian cancer. Studies of CD146 expression and function in breast cancer remain scarce except for a report concluding that CD146 could act as a tumor suppressor in breast carcinogenesis. METHODS: To resolve these apparent discrepancies in the role of CD146 in tumor cells, we looked at the association of CD146 expression with histoclinical features in human primary breast cancers using DNA and tissue microarrays. By flow cytometry, we characterized CD146 expression on different breast cancer cell lines. Using siRNA or shRNA technology, we studied functional consequences of CD146 downmodulation of MDA-MB-231 cells in migration assays. Wild-type, mock-transfected and downmodulated transfected cells were profiled using whole-genome DNA microarrays to identify genes whose expression was modified by CD146 downregulation. RESULTS: Microarray studies revealed the association of higher levels of CD146 with histoclinical features that belong to the basal cluster of human tumors. Expression of CD146 protein on epithelial cells was detected in a small subset of cancers with histoclinical features of basal tumors. CD146+ cell lines displayed a mesenchymal phenotype. Downmodulation of CD146 expression in the MDA-MB-231 cell line resulted in downmodulation of vimentin, as well as of a set of genes that include both genes associated with a poor prognosis in a variety of cancers and genes known to promote cell motility. In vitro functional assays revealed decreased migration abilities associated with decreased CD146 expression. CONCLUSIONS: In addition to its expression in the vascular compartment, CD146 is expressed on a subset of epithelial cells in malignant breast. CD146 may directly or indirectly contribute to tumor aggressiveness by promoting malignant cell motility. Changes in molecular signatures following downmodulation of CD146 expression suggest that CD146 downmodulation is associated with the reversal of several biological characteristics associated with epithelial to mesenchymal transition, and the phenomenon associated with the metastatic process.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Frequency, prognostic impact, and subtype association of 8p12, 8q24, 11q13, 12p13, 17q12, and 20q13 amplifications in breast cancers

BACKGROUND: Oncogene amplification and overexpression occur in tumor cells. Amplification status may provide diagnostic and prognostic information and may lead to new treatment strategies. Chromosomal regions 8p12, 8q24, 11q13, 17q12 and 20q13 are recurrently amplified in breast cancers. METHODS: To assess the frequencies and clinical impact of amplifications, we analyzed 547 invasive breast tumors organized in a tissue microarray (TMA) by fluorescence in situ hybridization (FISH) and calculated correlations with histoclinical features and prognosis. BAC probes were designed for: (i) two 8p12 subregions centered on RAB11FIP1 and FGFR1 loci, respectively; (ii) 11q13 region centered on CCND1; (iii) 12p13 region spanning NOL1; and (iv) three 20q13 subregions centered on MYBL2, ZNF217 and AURKA, respectively. Regions 8q24 and 17q12 were analyzed with MYC and ERBB2 commercial probes, respectively. RESULTS: We observed amplification of 8p12 (amplified at RAB11FIP1 and/or FGFR1) in 22.8%, 8q24 in 6.1%, 11q13 in 19.6%, 12p13 in 4.1%, 17q12 in 9.9%, 20q13(Z )(amplified at ZNF217 only) in 9.9%, and 20q13(Co )(co-amplification of two or three 20q13 loci) in 8.5% of cases. The 8q24, 12p13, and 17q12 amplifications were correlated with high grade. The most frequent single amplifications were 8p12 (9.8%), 8q24 (3.3%) and 12p13 (3.3%), 20q13(Z )and 20q13(Co )(1.6%) regions. The 17q12 and 11q13 regions were never found amplified alone. The most frequent co-amplification was 8p12/11q13. Amplifications of 8p12 and 17q12 were associated with poor outcome. Amplification of 12p13 was associated with basal molecular subtype. CONCLUSION: Our results establish the frequencies, prognostic impacts and subtype associations of various amplifications and co-amplifications in breast cancers

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Le français : des mots de chacun, une langue pour tous

Vraie problématique linguistique, socio-économique et culturelle que traitent dans ce volume des chercheurs et des universitaires, des enseignants et des hommes d’affaires, des juristes et des écrivains. Comment faire pour que les mots spécialisés de nos professions, ancrés dans des savoir-faire, deviennent également les formes ouvertes d’une langue à partager ? Comment faire aussi pour que les mots de tous les jours, ceux des enfants des banlieues comme ceux des fils de la terre, soient les gages d’une compréhension et d’une reconnaissance mutuelles, d’un accès à la langue des pères, dans une société en perpétuel mouvement ? Comment faire encore pour mettre en résonance les accents des français régionaux et les échos lointains des français de la francophonie, afin que se déploie plus largement cet idéal linguistique commun ? Autant de questions qui trouvent leur champ de réflexion et leur voie de réponse dans les différentes parties de cet ouvrage : le lecteur chemine d’abord à travers les accents du français parlé, en France et dans la francophonie, pénètre au cœur des particularités de l’écrit, réfléchit aux conditions des échanges et du partage de la langue pour pénétrer enfin dans le monde des poètes et s’initier aux enchantements de la langue littéraire qui n’a cessé de dire la vie, la jouissance et la fortune des mots d’où qu’ils proviennent, ceux de La Pléiade, archaïques, techniques ou dialectaux, ceux des poètes modernes, riches de sensations, constellés d’associations, pleins de fulgurances, ceux de Léopold Sedar Senghor, vibrant aux accords de l’Afrique et de la France, fondues dans une mythologie neuve, faite de valeurs singulières mais partagées, métissées par deux cultures dans une même vision poétique. Finalement, c’est encore là une belle escale dans le temps et l’espace que cette troisième étape du voyage au long cours que constituent les Lyriades renouvelées de la langue française. Cet ouvrage est issu des 3e journées de la langue française, Les Lyriades, qui se sont tenues à Liré en Anjou, les 19-20-21 mai 2006. Il a été conçu sous la direction de Françoise Argod-Dutard, professeur des universités et responsable du comité scientifique avec la collaboration de Dominique Beaumon, coordonnateur des Lyriades