Brain Metastasis Prediction by DASL Transcriptomic Profiling in Triple Negative Breast Cancer based on FFPE samples

Triple negative breast cancer (TNBC) lacks expression of steroid hormone receptors (estrogen alpha and progesterone) and epidermal growth factor receptor type 2. This phenotype shows high metastatic potential, with particular predilection to lungs and brain. Determination of transcriptomic profiles specific for brain metastasis (BM)-prone TNBC might identify high-risk patients requiring the use of alternative, more aggressive or specific preventive and therapeutic approaches. The aim of the study was to compare the gene expression profile in the primary tumor of patients who developed brain metastases in comparison to these who were metastatic to other organs (excluding central nervous system) in an attempt to verify, whether there exist a significant difference in the transcriptome of these two subgroups. Gene expression profiles of primary tumors in 71 TNBC patients (23 patients with BM and 48 patients without BM, discovery cohort), derived from a consecutive series of 324 advanced TNBC treated in 17 oncology centers in Poland and Italy between 1997 and 2013. Analysis was carried out in mRNA samples isolated from formalin-fixed paraffin embedded (FFPE) specimens, using Illumina cDNA-mediated Annealing, Selection, Extension and Ligation (DASL) method and Illumina HumanHT-12 oligonucleotide microarrays. The expression of 29,369 gene transcripts was compared between patients with and without BM, no reliable differences were identified. The results were validated in independent cohort of 48 samples, the top transcripts selected in discovery cohort showed no significant differences in the test set.