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Staining a tissue slice with antibodies so a protein shows up in colour under the microscope.
Immunohistochemistry (IHC) stains a thin slice of tissue with antibodies so that a chosen protein shows up in colour under the microscope. Scoring is semi-quantitative, from 0 through 1+ and 2+ to 3+, and it is the basis of ER, PR, HER2 and PD-L1 testing. Results suffer from pre-analytic variability and inter-observer disagreement, especially at the low end where HER2 0 must be told from 1+, and AI quantification is improving reproducibility. The term is tied to the Histopathology & immunohistochemistry and Digital pathology & AI technologies and to the bottleneck on unvalidated biomarkers, and ideas that build on it include AI quantification of HER2-low and calibrated reference slides for HER2-low scoring. It features in the DESTINY-Breast04, DESTINY-Breast06 and SPOTLIGHT papers.
Showing the technology this term belongs to: Histopathology & immunohistochemistry.
The glossary entry explains the word; the readout page carries the scoring rule, the thresholds approvals use, the companion diagnostics and the tests.
The 48 most recent of 54 papers; see them all →
Three-quarters of chemotherapy-naive TNBC would be low or ultralow by the DESTINY-Breast06 definitions, but ultralow is unlabelled in TNBC and carries no prognostic weight.
A direct check of the HERIZON-BTC-01 testing algorithm in routine pathology: IHC 3+ can stand alone, 2+ needs ISH, and the low-level amplification in weakly stained tumours is the group where HER2 drugs are least likely to help.
Patients with hormone-receptor-positive metastatic breast cancer that has stopped responding to endocrine therapy can be offered trastuzumab deruxtecan as their first chemotherapy-type treatment if the tumour shows any HER2 staining, rather than waiting until after conventional chemotherapy. Whether to use it before or after chemotherapy is now a choice, since overall survival was not shown to differ and the drug carries a risk of lung inflammation.
For hormone-receptor-positive metastatic breast cancer that has already had chemotherapy, Dato-DXd controls the disease for longer with fewer severe side effects than chemotherapy, but does not help patients live longer, so it is not a standard option here. The result is a reminder that progression-free survival is a surrogate; regulators and clinicians should wait for survival data before adopting an ADC in a setting where later therapies are effective.
This is the population-based prevalence for the two label thresholds in early TNBC, and it shows the KEYNOTE-355 CPS 10 gate would admit only about a quarter of unselected patients.
Patients with newly diagnosed advanced stomach cancer should now have Claudin 18.2 tested alongside HER2, PD-L1 and mismatch repair, because roughly a third will be eligible for zolbetuximab, which adds about three months of median survival. The main practical problem is nausea and vomiting during infusions, which needs aggressive prophylaxis. How to sequence or combine it with immunotherapy in PD-L1-positive tumours is unresolved.
Patients whose breast cancer was previously called HER2-negative may now be eligible for an effective HER2-directed drug if their tumour has even low-level HER2 staining, so pathology reports must now distinguish HER2-low (1+ or 2+/ISH-negative) from HER2-zero. This applies to metastatic disease after at least one line of chemotherapy; it does not mean these patients benefit from trastuzumab or other older HER2 drugs.
Adjuvant immunotherapy entered lung cancer here, and with it the question that still divides practice: whether it is better given before the operation, after it, or on both sides.
Shares Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status, Re-test the metastasis, not the old primary, before every change of treatment, Overexpression, Calibrated reference slides so every lab scores HER2-low the same way.
Shares Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer, SS18::SSX fusion (synovial sarcoma), HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?, HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP.
Shares Clinical relevance of PD-L1 expression in gallbladder cancer: a potential target for therapy, Immune microenvironment in gallbladder adenocarcinomas, Programmed death ligand-1 (PD-L1) is an independent negative prognosticator in Western-world gallbladder cancer, A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer.
Shares Overexpression of the HER2/neu gene: a new therapeutic possibility for patients with advanced gallbladder cancer, Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer, Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status, Overexpression.
Shares Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status, Calibrated reference slides so every lab scores HER2-low the same way, HER2 IHC 1+, HER2 IHC 0 (HER2-negative, including ultralow).
Shares HER2 IHC 1+, HER2 IHC 0 (HER2-negative, including ultralow), HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP, HER2-ultralow (IHC 0 with membrane staining).
Shares International validation of the consensus Immunoscore for the classification of colon cancer, No specific molecular profile (NSMP) endometrial cancer, Deficient mismatch repair system in patients with sporadic advanced colorectal cancer, Integrative analyses of colorectal cancer show Immunoscore is a stronger predictor of patient survival than microsatellite instability.
Shares HER2 overexpression and amplification as a potential therapeutic target in colorectal cancer: analysis of 3256 patients enrolled in the QUASAR, FOCUS and PICCOLO colorectal cancer trials, HER2 status in extrahepatic cholangiocarcinoma and gallbladder carcinoma: concordance between immunohistochemistry and chromogenic in situ hybridization in 140 cases, Assessment of a HER2 scoring system for colorectal cancer: results from a validation study, HER2 IHC 2+ (equivocal, reflex to ISH).