# HER2 IHC 3+ (HER2-positive by immunohistochemistry)

Source: https://onco.cc/biomarkers/her2-ihc-3-plus/  
OnCo record `her2-ihc-3-plus` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

IHC 3+ means strong, complete membrane staining for HER2 in more than 10 percent of tumour cells. It is HER2-positive without needing a gene test and is the gate for trastuzumab, its combinations and antibody-drug conjugates in breast, stomach, biliary and, since 2024, any solid tumour.

## Summary

Under the ASCO/CAP guideline an IHC score of 3+ is circumferential membrane staining that is complete, intense and in more than 10 percent of tumour cells; 3+ is HER2-positive on its own, 2+ is equivocal and goes to in situ hybridisation, 0 and 1+ are negative for trastuzumab purposes. Trastuzumab, pertuzumab, trastuzumab emtansine, tucatinib, margetuximab and neratinib are labelled for HER2-positive (overexpressing or amplified) breast cancer; trastuzumab is labelled for HER2-overexpressing gastric or GEJ adenocarcinoma, where the gastric scoring rules allow incomplete basolateral staining. Trastuzumab deruxtecan is labelled for HER2-positive (IHC 3+ or ISH+) breast cancer and, tumour-agnostically, for HER2-positive (IHC 3+) solid tumours after prior therapy, where the label notes no FDA-authorised test yet exists. Zanidatamab is labelled for HER2-positive (IHC 3+) biliary tract cancer and, with chemotherapy, IHC 3+ gastro-oesophageal adenocarcinoma.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: HER2 IHC 3+; HER2 3+; IHC 3+; HER2 overexpression; HER2-positive IHC; HER2 protein overexpression
- Tags: biomarker; her2

## Notes

- Colorectal cancer: the colorectal-specific rule requires intense membranous staining in more than 50% of cells, against the 10% used in gastric cancer, because the colorectal-specific criteria were written and validated separately on 256 archival and 830 screening samples (Valtorta 2015). Overexpression was found in 2.2% of stage IV and 1.3% of stage II-III patients, and rose to 5.2% in KRAS and BRAF wild-type stage IV disease (Richman 2016).
- Gallbladder and biliary cancer: HERIZON-BTC-01 confirmed ERBB2 amplification by central in situ hybridisation and treated IHC 2+ or 3+ as HER2-positive (Harding 2023); the zanidatamab label requires IHC 3+ with the Ventana PATHWAY 4B5 assay. Scoring follows the gastro-oesophageal guideline, which accepts incomplete basolateral staining. In 140 resected biliary cancers 6.4% were 3+, every 3+ tumour was amplified, and staining often involved under half of tumour cells (Angerilli 2026); heterogeneity was seen in 83% of HER2-positive biliary cancers, with loss in deeper invasive areas (Hiraoka 2020). In the DESTINY-PanTumor02 biliary cohort the objective response rate was 56.3% in centrally confirmed IHC 3+ tumours against 22.0% overall (Oh 2026).

## Sources

- ENHERTU prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6
- Herceptin prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=492dbdb2-077e-4064-bff3-372d6af0a7a2
- ASCO/CAP HER2 testing in breast cancer guideline, 2018 focused update (Wolff et al., J Clin Oncol): https://doi.org/10.1200/JCO.2018.77.8738

## Connected records

- biomarkers: [Claudin 18.2 expression (>= 75% of tumour cells, moderate to strong)](https://onco.cc/biomarkers/cldn18-2-expression/), [HER2 (ERBB2) activating mutation](https://onco.cc/biomarkers/her2-mutation/), [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 ISH amplified (ERBB2 gene amplification)](https://onco.cc/biomarkers/her2-ish-amplified/), [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/), [HER3 expression](https://onco.cc/biomarkers/her3-expression/)
- cancers: [Biliary tract cancer (all types)](https://onco.cc/cancers/biliary-tract-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Early HER2-positive breast cancer](https://onco.cc/cancers/her2-positive-early-breast-cancer/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [HER2-positive gastric cancer](https://onco.cc/cancers/gastric-her2-positive/), [Metastatic cancer (cancer that has spread)](https://onco.cc/cancers/metastatic-cancer/)
- drugs: [HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)](https://onco.cc/drugs/her2-testing-assays/), [Margetuximab](https://onco.cc/drugs/margetuximab/), [Neratinib](https://onco.cc/drugs/neratinib/), [Pertuzumab](https://onco.cc/drugs/pertuzumab/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/), [Trastuzumab emtansine](https://onco.cc/drugs/trastuzumab-emtansine/), [Tucatinib](https://onco.cc/drugs/tucatinib/), [Zanidatamab](https://onco.cc/drugs/zanidatamab/)
- terms: [Dual HER2 blockade](https://onco.cc/terms/dual-her2-blockade/), [HER2 testing in biliary tract cancer (IHC, ISH and NGS)](https://onco.cc/terms/her2-testing-in-biliary-cancer/), [HER2-positive (IHC 3+ or ISH-amplified)](https://onco.cc/terms/her2-positive/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- key papers: [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/), [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/), [Efficacy and safety of trastuzumab deruxtecan in patients with HER2-expressing biliary tract or pancreatic tumors: a subgroup analysis of DESTINY-PanTumor02](https://onco.cc/key-papers/paper-oh-destiny-pantumor02-biliary-pancreatic-esmo-open-2026/), [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/), [Trastuzumab deruxtecan in patients with HER2-positive advanced colorectal cancer (DESTINY-CRC02): primary results from a multicentre, randomised, phase 2 trial](https://onco.cc/key-papers/paper-destiny-crc02-lancet-oncol-2024/), [Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER)](https://onco.cc/key-papers/paper-strickler-mountaineer-tucatinib-trastuzumab-lancet-oncol-2023/), [Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study](https://onco.cc/key-papers/paper-harding-lancet-oncol/)
- targets: [HER2](https://onco.cc/targets/her2/)

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