# Immunohistochemistry (IHC)

Source: https://onco.cc/terms/ihc/  
OnCo record `ihc` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Staining a tissue slice with antibodies so a protein shows up in colour under the microscope.

## Summary

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.

## Fields

- Kind: Term
- Last checked: 2026-09-04
- Also known as: 0/1+; 1+/2+; 2+/3+; membrane staining; membranous staining; staining intensity

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Immunohistochemistry
- Wikipedia: https://en.wikipedia.org/wiki/Immunohistochemistry

## Connected records

- technologies: [Digital pathology & AI](https://onco.cc/technologies/digital-pathology-ai/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Cancer of unknown primary (CUP)](https://onco.cc/cancers/cancer-of-unknown-primary/), [Cancer of unknown primary, favourable subsets](https://onco.cc/cancers/cup-favourable-subsets/), [Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma)](https://onco.cc/cancers/cup-unfavourable/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [HER2-amplified colorectal cancer](https://onco.cc/cancers/her2-amplified-colorectal/), [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/), [Prostate cancer](https://onco.cc/cancers/prostate/), [Triple-negative breast cancer (TNBC)](https://onco.cc/cancers/tnbc/)
- key papers: [A prospective, multi-institutional, pathologist-based assessment of 4 immunohistochemistry assays for PD-L1 expression in non-small cell lung cancer](https://onco.cc/key-papers/paper-rimm-pd-l1-assay-comparison-jama-oncol-2017/), [Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010)](https://onco.cc/key-papers/paper-felip-impower010-adjuvant-atezolizumab-lancet-2021/), [American Society of Clinical Oncology/College Of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer](https://onco.cc/key-papers/paper-asco-cap-er-pr-testing-guideline-jco-2010/), [Assessment of a HER2 scoring system for colorectal cancer: results from a validation study](https://onco.cc/key-papers/paper-valtorta-her2-scoring-colorectal-heracles-mod-pathol-2015/), [Atezolizumab for first-line treatment of PD-L1-selected patients with NSCLC](https://onco.cc/key-papers/paper-herbst-impower110-atezolizumab-pd-l1-nejm-2020/), [Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer](https://onco.cc/key-papers/paper-bardia-ascent-trop2-biomarker-ann-oncol-2021/), [CheckMate 026: first-line nivolumab in stage IV or recurrent non-small-cell lung cancer](https://onco.cc/key-papers/paper-checkmate-026-first-line-nivolumab-nejm-2017/), [Clinical relevance of PD-L1 expression in gallbladder cancer: a potential target for therapy](https://onco.cc/key-papers/paper-neyaz-pdl1-gallbladder-histopathology-2018/), [Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer](https://onco.cc/key-papers/paper-schettini-her2-low-features-npj-breast-cancer-2021/), [Clonal history and genetic predictors of transformation into small-cell carcinomas from lung adenocarcinomas](https://onco.cc/key-papers/paper-lee-clonal-history-small-cell-transformation-jco-2017/), [Combined tumour suppressor defects characterise clinically defined aggressive variant prostate cancers](https://onco.cc/key-papers/paper-aparicio-aggressive-variant-prostate-tumour-suppressors-ccr-2016/), [Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms](https://onco.cc/key-papers/paper-sigurjonsdottir-sp142-22c3-tnbc-bcr-2023/), [Deficient mismatch repair system in patients with sporadic advanced colorectal cancer](https://onco.cc/key-papers/paper-koopman-deficient-mismatch-repair-advanced-colorectal-bjc-2009/), [DESTINY-Breast04: trastuzumab deruxtecan works in HER2-low breast cancer, creating a new treatable group](https://onco.cc/key-papers/paper-destiny-breast04-nejm-2022/), [DESTINY-Breast06: trastuzumab deruxtecan before any chemotherapy in hormone-receptor-positive, HER2-low or ultralow breast cancer](https://onco.cc/key-papers/paper-destiny-breast06-nejm-2024/), [Details of human epidermal growth factor receptor 2 status in 454 cases of biliary tract cancer](https://onco.cc/key-papers/paper-hiraoka-her2-status-biliary-hum-pathol-2020/), [DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer](https://onco.cc/key-papers/paper-iacobuzio-donahue-dpc4-failure-pattern-autopsy-jco-2009/), [Exploring the spectrum of HER2 in non-metastatic triple negative breast cancer: from HER2-null to HER2-low, including HER2-ultralow status](https://onco.cc/key-papers/paper-boissiere-michot-her2-ultralow-tnbc-virchows-arch-2026/), [Galon 2006: the type, density and location of immune cells in colorectal tumours predict outcome](https://onco.cc/key-papers/paper-galon-immune-contexture-colorectal-science-2006/), [GATA6 expression distinguishes classical and basal-like subtypes in advanced pancreatic cancer](https://onco.cc/key-papers/paper-okane-gata6-basal-like-compass-ccr-2020/), [Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma](https://onco.cc/key-papers/paper-mok-ipass-gefitinib-pulmonary-adenocarcinoma-nejm-2009/), [Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer](https://onco.cc/key-papers/paper-foulkes-brca1-basal-phenotype-jnci-2003/), [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](https://onco.cc/key-papers/paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016/), [HER2 status in extrahepatic cholangiocarcinoma and gallbladder carcinoma: concordance between immunohistochemistry and chromogenic in situ hybridization in 140 cases](https://onco.cc/key-papers/paper-angerilli-her2-ihc-cish-biliary-hum-pathol-2026/), [HER2/HER3 pathway in biliary tract malignancies; systematic review and meta-analysis: a potential therapeutic target?](https://onco.cc/key-papers/paper-galdy-her2-biliary-tract-meta-analysis-cancer-metastasis-rev-2017/), [Identification of Lynch syndrome among patients with colorectal cancer](https://onco.cc/key-papers/paper-moreira-lynch-syndrome-identification-jama-2012/), [Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer](https://onco.cc/key-papers/paper-soda-eml4-alk-fusion-nature-2007/), [Immune microenvironment in gallbladder adenocarcinomas](https://onco.cc/key-papers/paper-patil-gallbladder-immune-microenvironment-aimm-2021/), [Integrative analyses of colorectal cancer show Immunoscore is a stronger predictor of patient survival than microsatellite instability](https://onco.cc/key-papers/paper-mlecnik-immunoscore-msi-colorectal-immunity-2016/), [International validation of the consensus Immunoscore for the classification of colon cancer](https://onco.cc/key-papers/paper-pages-immunoscore-international-validation-lancet-2018/), [IPATential150: ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer](https://onco.cc/key-papers/paper-ipatential150-ipatasertib-abiraterone-pten-lancet-2021/), [KEYNOTE-010 (Herbst 2016): pembrolizumab versus docetaxel in previously treated PD-L1-positive lung cancer](https://onco.cc/key-papers/paper-keynote-010-lancet-2016/), [KEYNOTE-024: pembrolizumab alone beats chemotherapy in PD-L1-high lung cancer](https://onco.cc/key-papers/paper-keynote-024-nejm-2016/), [MET exon 14 mutations in non-small-cell lung cancer are associated with advanced age and stage-dependent MET genomic amplification and c-Met overexpression](https://onco.cc/key-papers/paper-awad-met-exon-14-mutations-lung-jco-2016/), [Molecular biomarkers for the evaluation of colorectal cancer: guideline from ASCP, CAP, AMP and ASCO](https://onco.cc/key-papers/paper-sepulveda-molecular-biomarkers-colorectal-guideline-jco-2017/), [MSH2 loss in primary prostate cancer](https://onco.cc/key-papers/paper-guedes-msh2-loss-primary-prostate-ccr-2017/), [Overexpression of the HER2/neu gene: a new therapeutic possibility for patients with advanced gallbladder cancer](https://onco.cc/key-papers/paper-roa-her2-overexpression-gallbladder-gcr-2014/), [PD-L1 Immunohistochemistry Assay Comparison in Atezolizumab Plus nab-Paclitaxel-Treated Advanced Triple-Negative Breast Cancer](https://onco.cc/key-papers/paper-rugo-pd-l1-assay-comparison-impassion130-jnci-2021/), [PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project](https://onco.cc/key-papers/paper-hirsch-j-thorac-oncol/), [PD-L1 immunohistochemistry comparability study in real-life clinical samples: results of Blueprint phase 2 project](https://onco.cc/key-papers/paper-blueprint-phase-2-pd-l1-assays-jto-2018/), [Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast cancer](https://onco.cc/key-papers/paper-gucalp-bicalutamide-ar-positive-tbcrc011-ccr-2013/), [Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression](https://onco.cc/key-papers/paper-crane-smad4-progression-pattern-locally-advanced-jco-2011/), [Programmed death ligand-1 (PD-L1) is an independent negative prognosticator in Western-world gallbladder cancer](https://onco.cc/key-papers/paper-albrecht-pdl1-western-gallbladder-cancers-2021/), [Proposed morphologic classification of prostate cancer with neuroendocrine differentiation](https://onco.cc/key-papers/paper-epstein-neuroendocrine-prostate-morphologic-classification-ajsp-2014/), [Prostate-specific membrane antigen expression in normal and malignant human tissues](https://onco.cc/key-papers/paper-silver-psma-expression-normal-malignant-tissues-ccr-1997/), [PTEN protein loss and clinical outcome from castration-resistant prostate cancer treated with abiraterone acetate](https://onco.cc/key-papers/paper-ferraldeschi-pten-protein-loss-abiraterone-eur-urol-2015/), [Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study](https://onco.cc/key-papers/paper-carey-race-breast-cancer-subtypes-cbcs-jama-2006/), [SCLC subtypes defined by ASCL1, NEUROD1, POU2F3, and YAP1: a comprehensive immunohistochemical and histopathologic characterization](https://onco.cc/key-papers/paper-baine-sclc-subtype-immunohistochemistry-jto-2020/), [SPOTLIGHT: zolbetuximab, the first Claudin 18.2 antibody, added to chemotherapy in gastric cancer](https://onco.cc/key-papers/paper-spotlight-lancet-2023/), [The genomic landscape of SMARCA4 alterations and associations with outcomes in patients with lung cancer](https://onco.cc/key-papers/paper-schoenfeld-smarca4-alterations-lung-ccr-2020/), [The TMPRSS2-ERG rearrangement, ERG expression and prostate cancer outcomes: a cohort study and meta-analysis](https://onco.cc/key-papers/paper-pettersson-tmprss2-erg-outcome-meta-analysis-cebp-2012/), [ToGA (Bang 2010): trastuzumab with chemotherapy for HER2-positive advanced gastric cancer](https://onco.cc/key-papers/paper-toga-trastuzumab-gastric-lancet-2010/), [TROPION-Breast01: datopotamab deruxtecan versus chemotherapy in pretreated hormone-receptor-positive breast cancer, and why a PFS win did not translate to survival](https://onco.cc/key-papers/paper-tropion-breast01-jco-2024/), [Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors](https://onco.cc/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/)
- roadmaps: [Triple-negative breast cancer roadmap: from a remainder defined by three negative tests to immunotherapy, antibody-drug conjugates and the residual disease problem](https://onco.cc/roadmaps/tnbc-roadmap/)
- ideas: [AI quantification of HER2-low and HER2-ultralow](https://onco.cc/ideas/idea-ai-her2-low-scoring/), [Calibrated reference slides so every lab scores HER2-low the same way](https://onco.cc/ideas/idea-tr2-her2-low-reference-materials/), [Harmonise PD-L1 testing for triple-negative breast cancer around one scored assay, with external quality assurance](https://onco.cc/ideas/idea-tnbc-pd-l1-assay-harmonisation/), [Re-test the metastasis, not the old primary, before every change of treatment](https://onco.cc/ideas/idea-bio1-rebiopsy-before-switch/), [Record how long tissue waited before fixation in every pathology report](https://onco.cc/ideas/idea-tr2-preanalytics-in-report/), [Reflex HER2 testing of every advanced gallbladder and extrahepatic biliary cancer](https://onco.cc/ideas/idea-gbc-reflex-her2-testing-advanced-biliary/), [Reflex re-scoring of HER2 0 versus 1+ with digital assistance so every eligible triple-negative patient reaches trastuzumab deruxtecan](https://onco.cc/ideas/idea-tnbc-her2-ultralow-testing-uptake/), [Run small-cell lung cancer as one platform with shared controls and subtype stratification](https://onco.cc/ideas/idea-lung-small-cell-platform-with-shared-controls-and-subtypes/)
- terms: [BAP1 loss](https://onco.cc/terms/bap1-loss/), [Biomarker](https://onco.cc/terms/biomarker/), [Biopsy](https://onco.cc/terms/biopsy/), [CDKN2A/B homozygous deletion](https://onco.cc/terms/cdkn2a-homozygous-deletion/), [Cell of origin in practice: Hans against expression profiling, and what it changes](https://onco.cc/terms/lymphoma-bio-cell-of-origin-in-practice/), [Gene expression](https://onco.cc/terms/gene-expression/), [GIST risk stratification (mitotic count, size, site; Miettinen and modified NIH criteria)](https://onco.cc/terms/gist-risk-stratification/), [HER2 testing in biliary tract cancer (IHC, ISH and NGS)](https://onco.cc/terms/her2-testing-in-biliary-cancer/), [HER2 testing in the UK: reflex ISH, the ratio against the copy number, and where the UK differs from ASCO/CAP](https://onco.cc/terms/her2-testing-uk-breast/), [HER2-positive (IHC 3+ or ISH-amplified)](https://onco.cc/terms/her2-positive/), [HHV-8 (KSHV) status and LANA-1 immunohistochemistry](https://onco.cc/terms/hhv8-kshv/), [Histology](https://onco.cc/terms/histology/), [How ER and PR are scored on a breast report (Allred score, H score, and why PR is not a UK core item)](https://onco.cc/terms/er-pr-scoring-breast/), [Medulloblastoma molecular groups (WNT, SHH, group 3, group 4)](https://onco.cc/terms/medulloblastoma-molecular-groups/), [Merkel cell polyomavirus (MCPyV) status](https://onco.cc/terms/mcpyv-status/), [MLH1 promoter methylation (sporadic versus Lynch mismatch repair loss)](https://onco.cc/terms/mlh1-promoter-methylation/), [Neuroendocrine differentiation in prostate cancer](https://onco.cc/terms/neuroendocrine-differentiation/), [No specific molecular profile (NSMP) endometrial cancer](https://onco.cc/terms/nsmp/), [Overexpression](https://onco.cc/terms/overexpression/), [Protein](https://onco.cc/terms/protein/), [PTEN loss](https://onco.cc/terms/pten-loss/), [SDH deficiency (SDHB immunohistochemistry loss)](https://onco.cc/terms/sdh-deficiency/), [Small-cell lung cancer transcription-factor subtypes (SCLC-A, SCLC-N, SCLC-P, SCLC-I) and SLFN11](https://onco.cc/terms/sclc-molecular-subtypes/), [SS18::SSX fusion (synovial sarcoma)](https://onco.cc/terms/ss18-ssx-fusion/), [t(11;14), cyclin D1 and SOX11](https://onco.cc/terms/cyclin-d1-t11-14/)
- biomarkers: [c-Met protein overexpression (IHC 3+ in >= 50% of tumour cells)](https://onco.cc/biomarkers/met-overexpression/), [CD20 expression (CD20-positive)](https://onco.cc/biomarkers/cd20-expression/), [CD30 expression (CD30-positive)](https://onco.cc/biomarkers/cd30-expression/), [Claudin 18.2 expression (>= 75% of tumour cells, moderate to strong)](https://onco.cc/biomarkers/cldn18-2-expression/), [dMMR (mismatch repair deficiency by IHC)](https://onco.cc/biomarkers/dmmr-ihc/), [Double expressor: MYC and BCL2 protein together by immunohistochemistry](https://onco.cc/biomarkers/myc-bcl2-double-expressor/), [ER status (oestrogen receptor by IHC)](https://onco.cc/biomarkers/er-status/), [Folate receptor alpha expression (FRα-positive, PS2+ >= 75%)](https://onco.cc/biomarkers/folr1-expression/), [HER2 IHC 0 (HER2-negative, including ultralow)](https://onco.cc/biomarkers/her2-ihc-0/), [HER2 IHC 1+](https://onco.cc/biomarkers/her2-ihc-1-plus/), [HER2 IHC 2+ (equivocal, reflex to ISH)](https://onco.cc/biomarkers/her2-ihc-2-plus/), [HER2 IHC 3+ (HER2-positive by immunohistochemistry)](https://onco.cc/biomarkers/her2-ihc-3-plus/), [HER2-low (IHC 1+ or IHC 2+/ISH-negative)](https://onco.cc/biomarkers/her2-low-ihc/), [HER2-ultralow (IHC 0 with membrane staining)](https://onco.cc/biomarkers/her2-ultralow/), [Ki-67 index (proliferation by IHC)](https://onco.cc/biomarkers/ki-67-index/), [Nectin-4 expression](https://onco.cc/biomarkers/nectin-4-expression/), [PD-L1 CPS (combined positive score)](https://onco.cc/biomarkers/pd-l1-cps/), [PD-L1 IC score (immune-cell score, SP142)](https://onco.cc/biomarkers/pd-l1-ic-score/), [PD-L1 TC score (tumour-cell score, SP263 and 28-8)](https://onco.cc/biomarkers/pd-l1-tc-score/), [PD-L1 TPS (tumour proportion score)](https://onco.cc/biomarkers/pd-l1-tps/), [PR status (progesterone receptor by IHC)](https://onco.cc/biomarkers/pr-status/), [PTEN alteration (sequencing) and PTEN loss (IHC)](https://onco.cc/biomarkers/pten-alteration/), [TMPRSS2-ERG fusion (and the other ETS rearrangements)](https://onco.cc/biomarkers/tmprss2-erg-fusion/), [Treatment-emergent neuroendocrine transformation (recognising it)](https://onco.cc/biomarkers/nepc-transformation/), [TROP2 expression](https://onco.cc/biomarkers/trop2-expression/)
- targets: [Ki-67 (MKI67)](https://onco.cc/targets/mki67/), [Progesterone receptor (PGR)](https://onco.cc/targets/pgr/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/)
- drugs: [HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)](https://onco.cc/drugs/her2-testing-assays/), [PD-L1 IHC 22C3 pharmDx](https://onco.cc/drugs/dako-pd-l1-22c3-pharmdx/), [VENTANA PD-L1 (SP142) Assay](https://onco.cc/drugs/ventana-pd-l1-sp142/), [VENTANA PD-L1 (SP263) Assay](https://onco.cc/drugs/ventana-pd-l1-sp263/)

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