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Veripath OncoDiagnostics is equipped with state of the art technologies and extensive experience utilizing:
- Tissue Microrarrays
- Fluorescence in situ Hybridization on Paraffin Tissue
- Automated Immunohistochemistry
- Quantitative Immunohistochemistry
- Image Cytometry
- DNA Ploidy Analysis using Image Cytometry
It is a well-known paradigm that tumors may be heterogeneous with regards to expression of a given protein. On the contrary, normal tissues also express many of the products being measured in tumors. Thus, the use of homogenized fresh or frozen tissues means the results may be confounded by either tumoral heterogeneity or a complement of admixed non-neoplastic cells. Immunohistochemistry (IHC) bypasses this drawback since it is possible to determine the exact cell type expressing the protein of interest.
Many of the molecular abnormalities being studied in cancers are present in precancerous or even histologically normal tissues. Logistically, the specific isolation of these precancerous or normal tissues from the adjacent tumor for genetic analysis is difficult to impossible. In this context, IHC greatly facilitates the study of sequential appearance of abnormalities, albeit at the level of protein expression, in the multistage progression of cancers.
From a functional point of view, it is known that there are several mechanisms by which levels of the end product (protein expression) may be modulated upstream. This includes gene mutations, allelic deletions, promoter hypermethylation, post-transcriptional modifications etc. IHC can determine the levels of end product in tissues irrespective of the upstream mechanism modulating expression, and thus bypasses the need for analyzing these pathways individually. Thus IHC provides a more "wholistic" information than would be provided by any one genetic analysis alone.
A corollary of the feasibility of IHC application to archival tissues means that large-scale retrospective analyses can now be performed, with patient follow-up extending into years rather than weeks or months. This has resulted in a plethora of studies comparing protein expression in tumors with clinicopathologic parameters (overall survival, disease free survival, clinical stage etc.), and the consequent development of tumor-specific IHC panels. Needless to say, this is an expanding area, and as new proteins whose functions are abrogated in tumors are discovered, the search for better and more discriminating IHC markers of prognosis will continue.
One of the biggest drawbacks of IHC till date has been the absence of reliable quantitation criteria for determining levels of protein expression. Studies have used anywhere from two- to five-tier schemes for manually grading intensity of expression, and understandably there is considerable confusion and conflicting results in the literature resulting from this arbitrariness. This drawback is now being surpassed by the introduction of automated image analysis software that make the results reproducible and considerably diminish the elements of intra- and interobserver variability; Veripath OncoDiagnostics is especially equipped and experienced in doing these quantitative analyses on tissues.
For more information contact the Medical Director, Dr. Raheela Ashfaq at Veripath OncoDiagnostics.
214-645-7026.
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