Biomarker Panel for Differentiation of Wild Type and Breast Cancer Susceptibility Gene (BRCA) Mutated Breast Cancer

miRNA SSNA in situ Hybridization System

Breast cancer represents a heterogeneous group of tumors characterized by a wide range of clinical, pathologic and molecular features. Genetic susceptibility to breast cancer is highly increased with mutations in breast cancer susceptibility genes (BRCA1 and BRCA2). BRCA mutated breast carcinomas are commonly seen in younger patients and have a more aggressive clinical course. Identifying genomic biomarkers for breast cancer prognosis will lead to a better understanding of breast cancer genetics and a more accurate understanding of tumor behavior. Utilizing microRNAs (miRNAs) as a potential biomarker to differentiate BRCA will allow for specialized treatment regimens and increased clinical care. miRNAs are small, evolutionarily conserved, noncoding RNAs that negatively regulate gene expression and have fundamental roles in cancer growth and metastasis. miRNAs exert their function via base pairing with complementary mRNA molecules, resulting in gene silencing via transcriptional repression or target degradation. Owing to their stability in biological fluids and resistance to various storage conditions, miRNAs are considered as useful biomarkers for cancer diagnosis, prognosis, and prediction of treatment efficacy. Dysregulation of miRNA has been widely reported in many cancer types, including breast cancer. Recent studies have tested miRNAs as predictive biomarkers for determining BRCA mutated patient’s prognosis. Although numerous methods are available for gaining information about miRNA signatures, in situ hybridization (ISH) assay is a powerful tool that allows direct assessment of malignant cells. Unlike PCR based techniques, ISH system has the ability to generate a robust chromogenic signal while preserving the spatial context of the tissue sample thus allowing precise tumor characterization.

BioGenex is pleased to launch two Super Sensitive Nucleic Acid miRNA in situ hybridization (SSNA miRNA ISH) probes and automated systems for differentiation of wild type and BRCA mutated breast cancer. BioGenex unique SSNA miRNA ISH probes enable detection of single nucleotide mismatch thus allowing high sensitivity and specificity with a clean intense staining. BioGenex miRNA ISH Panel Probes are currently one of the best products for complex diagnostic assays. Over 240 ready-to-use (RTU) miRNA probes are now available, and more are being developed. BioGenex SSNA miRNA probes combined with the automated processing using Xmatrx® greatly increases the reliability of the test results through the elimination of error-prone ISH procedure. BioGenex fully-automated molecular pathology workstations are the most advanced system globally.

Using BioGenex ISH miRNA probes, the expression pattern of distinct miRNAs were successfully differentiated in wild type and BRCA mutated breast carcinomas. The miRNA expression profile was evaluated in formalin-fixed paraffin-embedded (FFPE) invasive ductal carcinoma cases containing BRCA mutated and wild type breast carcinomas (1). Differential expression of miRNA was documented using the BioGenex Xmatrx® automated system and miRNA ISH BRCA breast panel probes. The in situ experimental conditions for hybridization were optimized for both manual and automated systems. As compared with wild type breast cancer, expression of miR-17 and miR-21 was downregulated in BRCA mutated breast cancer, suggesting that the miRNA expression pattern may serve as a potential biomarker in predicting BRCA mutation status in invasive breast cancer. miR-17 has been linked to tumorigenesis in a broad range of cancers, including gastric cancer (2), and colon cancer (3). In a recent study, miR-17 has been shown to play a significant role in breast cancer progression (4). Several studies have also reported miR-21 as a potential novel diagnostic biomarker for breast cancer (5, 6). A study by Wang et al suggests that circulating miR-21 could serve as a potential serum-based biomarker for breast cancer detection in the Chinese population, with 80.0% sensitivity and 87.7% specificity (6). Thus, understanding the relationship of the miRNA expression level to the BRCA mutation status can help develop effective targeted interventions and specialized treatment options.

Please click on above links to download Biomarker Panel and Application Note for Differentiation of triple-negative breast cancer.

BioGenex also has an extensive catalog of over 240 unique miRNA probes

References

1. Li Y et al. miR-221/222 promotes S-phase entry and cellular migration in control of basal-like breast cancer. Molecules. 2014;19:7122-37.
2. Huo L et al. MicroRNA expression profiling identifies decreased expression of miR-205 in inflammatory breast cancer. Mod Pathol. 2016;29:330-46.
3. Piovan C et al. Oncosuppressive role of p53-induced miR-205 in triple negative breast cancer. Mol Oncol. 2012;6:458-72.