Immunohistochemistry as a surrogate for molecular testing: a review

Area of Science:

• Molecular Pathology
• Cancer Diagnostics
• Biomarker Discovery

Background:

• Human neoplasms exhibit numerous genetic and epigenetic alterations requiring molecular identification.
• Immunohistochemistry (IHC) remains essential in diagnostic pathology despite advancements in molecular techniques.
• Emerging molecular era necessitates evaluation of established diagnostic methods like IHC.

Purpose of the Study:

• To evaluate the role and value of immunohistochemistry (IHC) as a surrogate for molecular techniques in diagnosing and classifying human neoplasms.
• To highlight IHC's utility in identifying chromosomal abnormalities and gene mutations.
• To assess IHC's potential in predicting therapeutic response and risk stratification.

Main Methods:

• Development and application of sensitive and specific antibodies.
• Detection of proteins overexpressed due to gene translocation or amplification.
• Visualization of mutant gene products and splice variants.
• Approximation of gene expression profiles for molecular classification.

Main Results:

• IHC serves as a legitimate surrogate for cytogenetic and in situ hybridization-based identification of chromosomal abnormalities.
• IHC effectively detects mutational events, including protein loss, overexpression, and visualization of mutant products.
• IHC approximates gene expression profiles, aiding in molecular classification and risk stratification of neoplasms.

Conclusions:

• Immunohistochemistry is a valuable molecular technique and a cost-effective screening modality for selected molecular tests.
• The continued relevance of IHC is contingent upon the development of companion tests for novel biomarkers.
• IHC's role may evolve as genomic sequencing costs and time constraints decrease.