HER2 IHC 2+ (equivocal, reflex to ISH)

aka HER2 IHC 2+, HER2 2+, IHC 2+, HER2 equivocal, 2+/ISH, IHC 2+/ISH-negative, IHC 2+/ISH+

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.

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.

Part ofHER2· ERBB2Other readoutsHER2 HER2 IHC 0 HER2 IHC 1+HER2 IHC 3+HER2 ISH amplified HER2-low HER2-ultralow All readouts

HER2: what it is and how drugs act on it · animated schematic, not to scale

Target · the protein and the cell it sits on
Drug · antibody, small molecule, cell or radioligand
Effect · signal, damage or kill

In plain words · A growth-signal receptor. Some cancers make far too much of it, and drugs that block it or use it as a docking site have transformed those cancers.

IHC score 2 approval thresholds

What it means for a patient

A 2+ result is not final. Your pathologist should run an ISH gene test on the same sample: if the HER2 gene is amplified the cancer is HER2-positive and trastuzumab-based treatment applies; if it is not, the cancer is HER2-low, which in breast cancer opens trastuzumab deruxtecan after earlier treatment.

Written only from the label or guideline text cited on this page. Not medical advice; your own report and the reading your team gives it come first.

Scoring rule

2+: weak to moderate complete membrane staining in more than 10 percent of tumour cells, or intense complete staining in 10 percent or fewer; classified equivocal and reflexed to in situ hybridisation.

“HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test”
ENHERTU prescribing information; scoring band from the ASCO/CAP 2018 guideline

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
IHC 2+/ISH+ (HER2-positive)	Trastuzumab deruxtecan	HER2-positive gastric cancer	FDA	label
IHC 2+/ISH- (HER2-low)	Trastuzumab deruxtecan	HER2-low and HER2-ultralow metastatic breast cancer	FDA	label

Drugs whose label names it

Trastuzumab deruxtecan

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
PATHWAY anti-Her2/neu (4B5) Rabbit Monoclonal Primary Antibody	Ventana Medical Systems (Roche)	Breast Cancer - Tissue	Trastuzumab deruxtecan	P990081/S047 (09/30/2022)

Tests that measure it

HercepTest PATHWAY anti-HER2/neu (4B5)HER2 IQFISH pharmDx and INFORM HER2 Dual ISH

Trials that name this readout

Matched on the name and aliases of the readout in the title, setting and summary of each trial; a match is a mention, not proof the readout was an entry criterion.