|Triple Negative Breast Cancer - Differentiation of TNBC (ER-, PR-, and HER2/neu-) using New miRNA Biomarker Panel
Ready-to-Use fully optimized SSNA miRNA in situ hybridization (ISH) kit
Like many cancers, breast cancers are highly diverse with a range of distinct clinical outcomes. Breast cancers dependent on hormone signaling (estrogen receptor [ER]/ progesterone receptor [PR]) or on epidermal growth factor receptor (HER2/neu) typically have the most positive prognosis. Tumors’ lacking these receptors expression, referred to as triple-negative breast cancer (TNBC), is a poorly differentiated, highly malignant, aggressive type of breast cancer associated with poor prognosis. TNBC represents approximately 10-20% of all cases of breast cancer and is characterized by shorter overall survival. TNBC has a higher mortality and risks of metastasis compared with other subtypes of breast cancer and currently have no specific targeted therapies available for treatment. The five-year survival rate for TNBC is around 77% versus 93% for other breast cancer types, and therefore correct diagnosis of TNBC cases at an early stage is critical for treatment effectiveness. Numerous studies have demonstrated that aberrantly expressed microRNAs (miRNAs) are involved in the pathogenesis of the aggressive TNBC phenotype. miRNAs are small, noncoding RNA molecules that are involved in many critical cellular processes including oncogenesis. Different cancer types and subtypes at different stages of progression display unique miRNA profiles that may be used as diagnostic, prognostic and therapeutic tools. The detection of miRNA in clinical samples has been difficult, requiring total RNA extracts which lack critical spatial information. However, in situ hybridization (ISH) assays have enabled the direct assessment of miRNA expression levels in formalin-fixed paraffin-embedded (FFPE) malignant tissues.
The miRNA expression profile was evaluated in 10 normal and 18 FFPE breast cancer tissues. Breast cancers were subtyped using immunostains for ER, PR, and HER-2/neu. Sub-categorization of breast cancer resulted in 5 ER/PR+, 5 Her2+, and 8 TNBC. Differential expressions of the miRNAs were documented using the super sensitive BioGenex Xmatrx® automated system and miRNA ISH TNBC panel probes. BioGenex miRNA ISH panel probes are currently one of the best products for complex diagnostic assays. In the TNBC samples, miR-21, miR-221, and miR-222 were strongly upregulated, while miR-205 was downregulated, suggesting differential miRNA expression pattern between the TNBC cells and other breast tumor tissues. miR-21 was upregulated in 50% (2/4), miR-221 in 50% (4/8) and miR-222 in 63% (5/8) of cases, while miR-205 was downregulated in 37.5% (3/8) of cases. Additional research has indicated that the overexpression of miR-221 and miR-222 is related to clinicopathological factors and prognosis of TNBC (1). While, previous studies have also noted the downregulation of miR-205 in TNBC (2, 3). These miRNA probes may hold promise as potential biomarkers and therapeutic targets for patients with TNBC.
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