Examination of formalin-fixed paraffin embedded (FFPE) tissues is the cornerstone for histological and molecular pathology diagnosis of solid tumors. High-throughput profiling experiments have linked altered expression of miRNAs to different types of cancer. Several methodologies have been applied to detect miRNAs in FFPE specimens. However, tumor tissues are a heterogeneous mixture of not only cancer cells, but also supportive and reactive tumor microenvironment elements. In this respect, in situ hybridization (ISH) assays have the unique feature of determining the cellular compartment(s) of altered miRNA expression.
Dartmouth scientists have now developed a combined ISH and immunohistochemical (IHC) assay to detect the distribution and differential expression of miRNAs and proteins within cancer tissues. By comparing cancerous and healthy tissue samples, a subset of cancer-associated miRNAs, including frequently down-regulated (e.g., miR-34a, miR-205 and miR-126) and up-regulated (e.g., miR-21, miR-155 and miR-10b) miRNAs and protein markers have been identified for a variety of cancers including breast, colorectal, lung, pancreas and prostate carcinomas. Despite the distinct histopathological alterations of each particular cancer type, general trends emerged that pinpointed to distinct source cells of altered miRNA expression. These results indicate a heterogeneous participation of miRNAs in carcinogenesis by intrinsically affecting cancer cell biology or by modulating stromal, vascular and immune responses. Accordingly, implementation of ISH in combination with IHC for the detection of miRNAs and clinically important protein markers in fixed specimens now provides a fluorescence-based multi-color ISH/IHC assay that is rapid, sensitive, compatible with current automated clinical IHC assays, and provides spatial characterization of miRNA expression. The combined ISH/IHC assay, miRNA and protein biomarkers can now be used in detecting, classifying, diagnosing, prognosing and treating cancer.
These findings are claimed in pending patent applications. We are seeking an industrial partner to further refine and market this technology. (Ref: J584)
Last Updated: 7/24/12