Clinical Applications and Interpretation Standards of Immunohistochemistry in Tumor Companion Diagnostics

The Role of Immunohistochemistry in Tumor Diagnosis and Classification

Immunohistochemistry (IHC) is one of the widely used techniques in tumor pathology diagnosis. By detecting the expression levels of specific proteins in tumor tissues, it assists in determining tumor origin, differentiation direction, and molecular subtypes. For example, in breast cancer, immunohistochemical detection of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) has become part of routine pathology reports. In fields such as lymphoma, lung cancer, and gastrointestinal tumors, different marker combinations help narrow the differential diagnosis.

Immunohistochemistry results often need to be corroborated with histomorphology and other molecular tests. Positivity or negativity of a single marker cannot be directly equated with a specific diagnosis; it requires comprehensive assessment in conjunction with clinical information, imaging, and pathological features. Therefore, pathologists should be familiar with the positive localization patterns and common pitfalls of each marker when interpreting slides.

Common Markers and Interpretation Criteria in Companion Diagnostics

Companion diagnostics refers to the use of in vitro diagnostic tests to select suitable populations for specific therapeutic drugs. Immunohistochemistry plays an important role in the detection of targets or immunotherapy-related markers such as HER2, PD-L1, ALK, and ROS1. Taking HER2 testing as an example, scoring is generally based on cell membrane staining completeness and intensity, classified as 0, 1+, 2+, and 3+, with 2+ often requiring further in situ hybridization verification. Different cancer types and different drugs may have different interpretation thresholds, and laboratories should establish interpretation criteria according to corresponding guidelines and reagent instructions.

PD-L1 immunohistochemical testing has attracted attention in immunotherapy decision-making for various solid tumors, but different antibody clones, different detection platforms, and different scoring systems may affect results. Therefore, reports should specify the antibody clone used, detection platform, and scoring method to ensure traceability of results.

Interpretation Standards and Quality Control Recommendations

The accuracy of immunohistochemistry companion diagnostics directly affects treatment decisions; therefore, both experimental procedures and interpretation processes should be strictly managed. Laboratories should regularly participate in external quality assessment, perform performance validation of detection systems, and retain positive, negative, and weak positive control slides. Interpretation personnel should receive standardized training and undergo regular consistency assessment. For cases near the cutoff value, review by multiple pathologists is recommended, with verification by other detection methods when necessary.

With the development of personalized therapy, the application of immunohistochemistry in companion diagnostics will further expand. Standardized testing and interpretation help provide more reliable information for clinical practice and avoid treatment selection bias caused by technical fluctuations.