Inflammatory versus non-inflammatory breast cancers

Inflammatory Breast Cancer (IBC) is the most aggressive form of breast carcinoma characterized by the rapid onset of inflammatory signs. The molecular fingerprint for this rare, severe and unique clinical entity is still not elucidated. The goal of the present work was to detect both gene expression levels and alternate RNA splice variants specific to IBC. Experimental Design: In order to identify differentially expressed genes and splicing events, we performed splice-sensitive array profiling using Affymetrix Exon Array and quantitative RT-PCR analyses in a large series of 177 IBC compared to 183 non-IBC. We also assessed the prognostic value of the identified candidate genes and splice variants. Results: A 5-splice signature (HSPA8, RPL10, RPL4, DIDO1 and EVL) was able to distinguish IBC from non-IBC tumors (p<10-7). This splice signature was associated with poor metastasis-free survival (MFS) in hormone receptor-negative non-IBC (p=0.02), whereas it had no prognostic value in IBC patients. A PAM analysis of deregulated genes in IBC compared to non-IBC identified a 10-gene signature highly predictive of IBC phenotype and conferring a poor prognosis in non-IBC. The most up-regulated genes in IBC were 3 hemoglobin genes able to highly discriminate IBC from non IBC (p<10-4). In epithelial breast tumor cells, Hb protein expression was confirmed by immunohistochemistry. Conclusions: IBC has a specific spliced transcript profile that deserves further functional studies. Above all, IBC is characterized by hemoglobin genes overexpression, a fact that may lead to increased tumor progression. If confirmed, hemoglobins may serve as therapeutic targets. Training set of 33 IBC and 28 non IBC