# HER2 IHC 2+ (equivocal, reflex to ISH)

Source: https://onco.cc/biomarkers/her2-ihc-2-plus/  
OnCo record `her2-ihc-2-plus` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

IHC 2+ is the in-between HER2 result: moderate staining that cannot be called positive or negative by eye, so the laboratory runs an ISH gene test. 2+ with amplification is HER2-positive; 2+ without it is HER2-low.

## Summary

A 2+ score is weak to moderate complete membrane staining in more than 10 percent of tumour cells (or intense complete staining in 10 percent or fewer) and is equivocal under ASCO/CAP; reflex in situ hybridisation decides. The result matters twice over: IHC 2+/ISH+ counts as HER2-positive for trastuzumab, pertuzumab, trastuzumab emtansine and trastuzumab deruxtecan, while IHC 2+/ISH- is one of the two HER2-low categories for trastuzumab deruxtecan after chemotherapy (DESTINY-Breast04) or after endocrine therapy (DESTINY-Breast06). In gastric cancer the trastuzumab label defines positivity as IHC 3+ or IHC 2+ with a positive ISH.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: HER2 IHC 2+; HER2 2+; IHC 2+; HER2 equivocal; 2+/ISH; IHC 2+/ISH-negative; IHC 2+/ISH+
- Tags: biomarker; her2

## Sources

- ENHERTU prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7e67e73e-ddf4-4e4d-8b50-09d7514910b6
- 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: [HER2 IHC 1+](https://onco.cc/biomarkers/her2-ihc-1-plus/), [HER2 IHC 3+ (HER2-positive by immunohistochemistry)](https://onco.cc/biomarkers/her2-ihc-3-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/)
- cancers: [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [HER2-low and HER2-ultralow metastatic breast cancer](https://onco.cc/cancers/her2-low-metastatic-breast-cancer/), [HER2-positive gastric cancer](https://onco.cc/cancers/gastric-her2-positive/)
- drugs: [HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH)](https://onco.cc/drugs/her2-testing-assays/), [Trastuzumab](https://onco.cc/drugs/trastuzumab/), [Trastuzumab deruxtecan](https://onco.cc/drugs/trastuzumab-deruxtecan/)
- terms: [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [HER2-low and HER2-ultralow](https://onco.cc/terms/her2-low/), [HER2-positive (IHC 3+ or ISH-amplified)](https://onco.cc/terms/her2-positive/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/)
- targets: [HER2](https://onco.cc/targets/her2/)

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