biomarkersBiomarker

HER2 ISH amplified (ERBB2 gene amplification)

aka HER2 ISH+, HER2 FISH positive, ERBB2 amplification, HER2 amplified, HER2/CEP17 ratio >= 2.0, HER2 gene amplification, HER2 Dual ISH

ISH counts copies of the HER2 gene in each tumour cell. A ratio of 2 or more against the chromosome 17 control, or 6 or more copies per cell, is amplified and HER2-positive whatever the protein stain showed.

In situ hybridisation (fluorescent FISH or chromogenic dual ISH) measures ERBB2 gene copies. Under ASCO/CAP 2018, a HER2/CEP17 ratio >= 2.0 with an average HER2 copy number >= 4.0 per cell is positive (group 1); a ratio < 2.0 with copy number >= 6.0 is positive (group 3); ratio >= 2.0 with copy number < 4.0 (group 2) and ratio < 2.0 with copy number 4.0 to < 6.0 (group 4) need concurrent IHC and are positive only if the IHC is 3+ (or 2+ on recount for group 4 in some readings). Labels for trastuzumab, pertuzumab, trastuzumab emtansine and trastuzumab deruxtecan accept ISH+ as HER2-positive; the FDA list carries the HER2 FISH pharmDx, PathVysion, INFORM HER-2/neu, SPOT-LIGHT CISH and Ventana Dual ISH kits as companion diagnostics.

Part ofHER2· ERBB2Other readoutsHER2 HER2 IHC 0 HER2 IHC 1+HER2 IHC 2+HER2 IHC 3+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.

ISH / FISH 3 approval thresholds

What it means for a patient

An amplified ISH result means your cancer has extra copies of the HER2 gene and is HER2-positive, so trastuzumab-based treatment applies even if the protein stain was only 2+. A non-amplified result after a 2+ stain means HER2-low. The ratio and copy number on the report are what the pathologist used; ask for them if the report only says positive or negative.

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

HER2/CEP17 ratio >= 2.0 with mean HER2 copy number >= 4.0 signals per cell is amplified; ratio < 2.0 with copy number >= 6.0 is also amplified; other combinations are resolved with concurrent immunohistochemistry.

“HER-2/neu (ERBB2) gene amplification (ISH amplified)”
FDA: List of FDA-Authorized Companion Diagnostic Devices

Thresholds used in approvals

Threshold	Drug	Cancer	Regulator	Source
ISH+ (IHC 3+ or ISH+)	Trastuzumab deruxtecan	HER2-positive breast cancer	FDA	label
HER2 gene amplification	Trastuzumab	HER2-positive breast cancer	FDA	label
HER2 gene amplification	Pertuzumab	HER2-positive breast cancer	FDA	label

Drugs whose label names it

Trastuzumab deruxtecan Trastuzumab Pertuzumab

Companion diagnostics (FDA list)

Device	Maker	Indication and sample	Drug	PMA / 510(k)
HER2 FISH pharmDx Kit	Dako Denmark A/S (Agilent)	Breast Cancer - Tissue	Trastuzumab	P040005 (05/03/2005)
HER2 FISH pharmDx Kit	Dako Denmark A/S (Agilent)	Gastric and Gastroesophageal Cancer - Tissue	Trastuzumab	P040005/S005 (10/20/2010)
PathVysion HER-2 DNA Probe Kit	Abbott Molecular	Breast Cancer - Tissue	Trastuzumab	P980024 (12/11/1998)
Ventana HER2 Dual ISH DNA Probe Cocktail	Ventana Medical Systems (Roche)	Breast Cancer - Tissue	Trastuzumab	P190031 (07/28/2020)
Ventana HER2 Dual ISH DNA Probe Cocktail	Ventana Medical Systems (Roche)	Breast Cancer - Tissue	Trastuzumab deruxtecan Pertuzumab	P190031/S014 (12/15/2025)

Tests that measure it

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.