Flagship Biosciences Evaluating Her2 RNA and Protein Expression

Recent Flagship Biosciences developments for evaluating Her2 with image analysis tools was presented at the annual AACR conference.

The research received some attention from Genetic Engineering & Biotechnology News.  In their May 15, 2013 (Vol. 33 No. 10) issue feature article, “Cancer Diagnostics, Pushing the Boundaries,” Vicki Glaser expands upon Flagship Biosciences’ use of the proprietary CellMapTM algorithm to quantify Her2 RNA and protein expression.  The editors at Genetic Engineering & Biotechnology News found Flagship Biosciences’ approaches to be cutting-edge as   CellMapTM algorithm derived mark-up images were placed on the cover page of their most recent issue. The poster, entitled “Tissue Image Analysis Tool to Quantify HER2 RNA and Protein Expression for Breast Cancer Diagnosis,” was a collaboration between scientists at Flagship Biosciences and Affymetrix/Panomics.  The poster describes how Flagship Biosciences’ CellMapTM algorithm was used to analyze Her2 RNA and protein levels in tissue microarrays and to successfully differentiate tumor cells from the normal surrounding tissue. These studies address the potential role of Her2 RNA in breast cancer diagnosis and are of high interest in biomarker research, drug discovery, and companion diagnostics.

See the poster here.

Read the original article here.

The following is an excerpt from the original article:

“Several presentations at the AACR meeting highlighted the application of molecular diagnostic tools in cancer R&D and product development for the oncology diagnostics market.

Mirza Peljto and co-authors from Flagship Biosciences and Affymetrix/Panomics described a method for the quantitative in situ assessment of oncogene RNA and protein expression in human clinical tumor tissue for use in biomarker and diagnostics development. In breast cancer, the Her2 oncogene is amplified or overexpressed in about 30% of breast cancers, but the correlation between Her2 gene expression and protein expression in these tumors is not well understood.

The researchers used chromogenic RNA in situ hybridization (CISH) and immunohistochemistry (IHC) to develop a quantitative image analysis-based assay in which the levels of Her2 protein and RNA can be compared in situ within tissue context. This approach allows for the measurement and correlation of Her2 RNA and membrane protein expression across an entire tissue section. “It improves diagnostic concordance by relying on an automated method and also improves confidence in interpretation by assessing every tumor cell across the whole slide,” said Peljto.

The authors were able to distinguish high- from low-expressing biopsy samples using the CellMap™ algorithm to analyze the digital images produced, to differentiate tumor cells from the normal surrounding tissue, and to transform the images into cell and biomarker maps and quantify the levels of RNA and protein biomarkers.

The authors reported 79% concordance between Her2 RNA and Her2 protein expression. The study results “suggest the potential use of RNA CISH in assessment of Her2 status in conjunction and/or parallel to IHC.” The authors drew the following conclusions: “We demonstrated practical feasibility of combined molecular and image analysis for analyzing clinical tumor samples. The inclusion of automated, whole-slide IHC and CISH interpretation for molecular assessment for companion diagnostics may help solve the long-standing problem of manual pathologist assessments and improve concordance with the inclusion of an RNA-based readout simultaneous to an IHC-based readout.”

Evaluating Her2