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Molecular Oncology, Markers, Clinical Correlates |
1 Laboratoire d’Oncogénétique - INSERM E0017, Centre René Huguenin, St-Cloud; 2 Laboratoire de Génétique Moléculaire - UPRES EA 3618, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris V, Paris; 3 Service d’Oncologie Médicale, Hôpital Saint-Louis, Paris; 4 Direction de la Recherche Thérapeutique, Institut Gustave Roussy, Villejuif, France
Purpose: Inflammatory breast cancer (IBC) is a rare but particularly aggressive form of primary breast cancer. The molecular mechanisms responsible for IBC are largely unknown.
Experimental Design: To obtain further insight into the molecular pathogenesis of IBC, we used real-time quantitative reverse transcription (RT)-PCR to quantify the mRNA expression of 538 selected genes in IBC relative to non-IBC.
Results: Twenty-seven (5.0%) of the 538 genes were significantly up-regulated in IBC compared with non-IBC. None were down-regulated. The 27 up-regulated genes mainly encoded transcription factors (JUN, EGR1, JUNB, FOS, FOSB, MYCN, and SNAIL1), growth factors (VEGF, DTR/HB-EGF, IGFBP7, IL6, ANGPT2, EREG, CCL3/MIP1A, and CCL5/RANTES) and growth factor receptors (TBXA2R, TNFRSF10A/TRAILR1, and ROBO2). We also identified a gene expression profile, based on MYCN, EREG, and SHH, which discriminated subgroups of IBC patients with good, intermediate, and poor outcome.
Conclusion: Our study has identified a limited number of signaling pathways that require inappropriate activation for IBC development. Some of the up-regulated genes identified here could offer useful diagnostic or prognostic markers and could form the basis of novel therapeutic strategies.
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