Why is it necessary to do genetic testing after immunohistochemistry?

Although there are many detection methods, such as immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), direct sequencing, real-time polymerase chain reaction (PCR), denaturing high-performance liquid chromatography (DHPLC), matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry, and next-generation sequencing (NGS), the most commonly used methods in lung cancer are IHC and NGS. So, what is the difference between the two? Why can't we just do one of the tests?

IHC vs. NGS: Who is the "superhero" in the testing world?

First, from a methodological perspective, IHC is like a sniper, accurately locating specific antigens in tissues or cells based on antigen antibodies, while NGS is more like a detective, determining the DNA sequence by capturing the special markers (usually fluorescent molecular markers) carried by the newly added bases during DNA replication.

In terms of detection targets, IHC can detect fewer targets than NGS, and can only detect some gene mutations (such as ALK translocation, MET overexpression) or programmed death ligand-1 (PD-L1) overexpression. However, in addition to the above sites, NGS can also detect mutations in more sites such as BRAF, ROS1, NTRK1, MET, KRAS, HER-2 and FGFR3, including point mutations, amplifications, fusions, etc.

Clinical guidance significance: Whose "battle map" is more detailed?

IHC markers can guide the specific pathological classification of lung cancer in routine clinical practice (such as TTF-1, Napsin A, CK5/6, P63 and P40, etc.). In addition to covering a wider range of genetic variations, NGS is also used to describe the scale and type of differences that occur in tumors and their microenvironments. For example, TMB testing can have a certain predictive potential for the response to immune checkpoint inhibitors. NGS's "battle map" is more detailed and can help doctors develop more accurate treatment plans.

Summary: IHC and NGS are indispensable!

In general, IHC is a test at the protein expression level, and NGS is a test at the gene level. The two complement and verify each other. Therefore, after doing IHC, it is also necessary to conduct further genetic testing.