Abstract
BackgroundDuctal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. We aimed to identify potential biomarkers that can predict invasiveness risk.MethodsIn this epithelial cell-based study archival formalin-fixed paraffin-embedded blocks from six patients diagnosed with invasive lesions (pure invasive ductal carcinoma), six with in-situ lesions (pure ductal carcinoma in situ), six with synchronous lesions (invasive ductal carcinoma with an in-situ component) and three non-neoplastic breast epithelium tissues were analyzed by gene expression profiling of 770 genes, using the nCounter® PanCancer Pathways panel of NanoString Technologies.ResultsThe results showed that in comparison with non-neoplastic tissue the pure ductal carcinoma in situ was one with the most altered gene expression profile. Comparing pure ductal carcinoma in situ and in-situ component six differentially expressed genes were found, three of them (FGF2, GAS1, and SFRP1), play a role in cell invasiveness. Importantly, these genes were also differentially expressed between invasive and noninvasive groups and were negatively regulated in later stages of carcinogenesis.ConclusionsWe propose these three genes (FGF2, GAS1, and SFRP1) as potential biomarkers of ductal carcinoma in situ progression, suggesting that their downregulation may be involved in the transition of stationary to migrating invasive epithelial cells.
Highlights
Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment
Putative genes involved in ductal carcinoma in situ (DCIS) progression Eleven comparisons were made two-by-two to obtain the Differently expressed gene (DEG) (p-value ≤0.01)
Between control and tumor tissues, the greatest differential expression was observed between DCISpure and control (123 DEGs - 72 downregulated), and the lowest, between control and IDCpure (66 DEGs - 46 downregulated)
Summary
Ductal carcinoma in situ is a non-obligate precursor of invasive breast carcinoma and presents a potential risk of over or undertreatment. Finding molecular biomarkers of disease progression could allow for more adequate patient treatment. Breast cancer (BC) begins as premalignant lesions, progressing to the preinvasive stage of ductal carcinoma in situ (DCIS) and culminating as invasive ductal carcinoma (IDC) [1, 2]. Gene expression profiling-based studies have shown that distinct stages of progression are evolutionary products of same clonal origin and that genes conferring invasive growth. Finding gene expression patterns that could predict invasive progression would allow us to personalize DCIS treatment to each patient’s real needs. Gene expression profiling was performed in non-neoplastic breast epithelium, pure DCIS, mixed lesions (DCIS-IDC) (IDC with an in-situ component)
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