Molecular determinants of the inflammatory breast cancer phenotype.
ABSTRACT Despite advances in multimodality treatment, inflammatory breast cancer (IBC) remains the most aggressive and lethal form of breast cancer. The use of primary human IBC cell lines and functional in vive xenograft cancer models have revealed characteristics innate to IBC thought to confer a strong metastatic potential and aggressive phenotype. Classic descriptive markers in IBC (e.g., estrogen and progesterone receptor status) often guide optimal therapy and aid in development of new diagnostic and prognostic technologies. Recent IBC research has examined two genes, RhoC GTPase and WISP3, which are concordantly altered in the majority of IBC tumors but not in non-IBC specimens. RhoC serves as a transforming oncogene by regulation of genes involved in the cell cycle, secretion of angiogenic factors, and activity of insulin-like growth factor (IGF). WISP3 functions as a tumor-suppressor gene by modulation of IGF activity and resultant inhibition of cell proliferation, growth, and angiogenesis. Continued research with molecular analysis technology is imperative in order to harness differential gene expression and fully discover a signature profile of IBC. The ultimate goal is to reveal the specific molecular determinants that underlie its aggressive phenotype so that we may accurately identify markers of disease, improve diagnostic tools and predictors of response to treatment, and even suggest targeted IBC-specific therapies that afford improved survival.
Full-textDOI: · Available from: Nathan W Houchens, Jul 23, 2014
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Article: Molecular determinants of the inflammatory breast cancer phenotype.
- SourceAvailable from: Zacharoula Sidiropoulou[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: Inflammatory breast cancer is a rare, yet controversial, syndrome of invasive breast cancer. CASE REPORT: A female, Caucasian, 57-year-old patient presented at the emergency department with complaints suggestive of inflammatory breast cancer. CONCLUSIONS: Inflammatory breast cancer, besides the advances on its molecular profile, still remains a clinical entity difficult to diagnose, especially in the primary health care setting.Breast Care 01/2009; 4(6):397-399. DOI:10.1159/000261505 · 0.91 Impact Factor
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ABSTRACT: The case definition for inflammatory breast cancer (IBC) is controversial. The American Joint Committee on Cancer defines IBC as redness, warmth and edema involving at least half the breast. The SEER program relies on a pathologic finding of dermal lymphatic invasion and recently added those with clinical involvement of more than 3/4 of the breast. We established a registry to collect information and specimens from IBC patients to clarify the epidemiology and biology of these tumors. The goals of this report are to suggest improvements regarding case definitions and provide data on the variety of presentations relevant to early diagnosis.03/2010; 2(1):143-152. DOI:10.3390/cancers2010143
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ABSTRACT: Inflammatory breast cancer (IBC) is an aggressive form of BC poorly defined at the molecular level. We compared the molecular portraits of 63 IBC and 134 non-IBC (nIBC) clinical samples. Genomic imbalances of 49 IBCs and 124 nIBCs were determined using high-resolution array-comparative genomic hybridization, and mRNA expression profiles of 197 samples using whole-genome microarrays. Genomic profiles of IBCs were as heterogeneous as those of nIBCs, and globally relatively close. However, IBCs showed more frequent "complex" patterns and a higher percentage of genes with CNAs per sample. The number of altered regions was similar in both types, although some regions were altered more frequently and/or with higher amplitude in IBCs. Many genes were similarly altered in both types; however, more genes displayed recurrent amplifications in IBCs. The percentage of genes whose mRNA expression correlated with CNAs was similar in both types for the gained genes, but ∼7-fold lower in IBCs for the lost genes. Integrated analysis identified 24 potential candidate IBC-specific genes. Their combined expression accurately distinguished IBCs and nIBCS in an independent validation set, and retained an independent prognostic value in a series of 1,781 nIBCs, reinforcing the hypothesis for a link with IBC aggressiveness. Consistent with the hyperproliferative and invasive phenotype of IBC these genes are notably involved in protein translation, cell cycle, RNA processing and transcription, metabolism, and cell migration. Our results suggest a higher genomic instability of IBC. We established the first repertory of DNA copy number alterations in this tumor, and provided a list of genes that may contribute to its aggressiveness and represent novel therapeutic targets.PLoS ONE 02/2011; 6(2):e16950. DOI:10.1371/journal.pone.0016950 · 3.53 Impact Factor