[Challenges of immunohistochemistry for individualized cancer chemotherapy]

The availability of companion biomarkers should improve chemotherapeutic effectiveness, decrease ad- verse effects, and lead to individualized cancer treatment. In this article, the role of immunohistochemistry (IHC) in detecting companion biomarkers is reviewed. The hormone receptor (HR) is a companion bi- omarker for hormonal therapy in breast cancers, and IHC is the standard assay for detecting HR expression. The overexpression/amplification of human epidermal growth factor receptor 2 (HER2) is predictive of a favorable response to anti-HER2 agents such as trastuzumab, lapatinib, and pertuzumab. IHC and fluorescent in situ hybridization (FISH) are used to determine the HER2 status. Non-small cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations respond to EGFR inhibitors such as gefitinib and erlotinib. Recently, mutated EGFRs have been detected by IHC with mutation-specific antibodies, although it shows a lower sensitivity and specificity than DNA sequencing. In addition, NSCLCs with the anaplastic lymphoma kinase (ALK) fusion gene are highly responsive to an ALK inhibitor, crizotinib. Companion diagnostic assays for crizotinib are IHC, FISH, and the reverse transcription-polymerase chain reaction. Most gastrointestinal stromal tumors (GISTs) have KIT or platelet-derived growth factor receptor a mutations, related to the effectiveness of imatinib. Thus, definite pathologic diagnosis using IHC is necessary for the appropriate treatment of GISTs. Rituximab, an anti-CD20 monoclonal antibody, improves the treatment outcome for patients with non-Hodgkin's lymphoma. In the field, confirmation of CD20 expression by IHC is necessary for application of the drug. Finally, the author discusses the possibility of being able to predict the response to cytotoxic agents using IHC of solute carrier transporters.