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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.
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.
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.
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| 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 |
| 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 deruxtecanPertuzumab | P190031/S014 (12/15/2025) |
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.
A direct check of the HERIZON-BTC-01 testing algorithm in routine pathology: IHC 3+ can stand alone, 2+ needs ISH, and the low-level amplification in weakly stained tumours is the group where HER2 drugs are least likely to help.
This is the paper Europe PMC returns for registry id NCT04744831 with the most citations, so it is the natural first reading for anyone following the DESTINY-CRC02 trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
The cleanest split of HER2 alterations in gallbladder cancer into amplification and mutation, which matters because IHC and ISH only see the amplified tumours. It also shows the high-incidence Chilean population has not been sequenced at scale.
The first United States approval of a HER2-directed regimen in colorectal cancer, and the basis for MOUNTAINEER-03, which is testing the combination with chemotherapy in the first line.
One cancer page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
It is the proof that plasma genotyping can enrol patients for a targeted colorectal trial, which matters most for a 2 to 3% alteration where archival tissue is often exhausted or out of date.
The first demonstration that HER2 is actionable in colorectal cancer, and the trial that defined the colorectal-specific HER2 scoring criteria every later trial has used.
It fixes the population size for HER2-directed therapy, shows the enrichment in wild-type disease that makes reflex HER2 testing worthwhile there, and establishes that HER2 is not itself prognostic in this cancer.
Shares HER2 IHC 2+ (equivocal, reflex to ISH), HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), HER2 IHC 3+ (HER2-positive by immunohistochemistry), Trastuzumab deruxtecan and the tags biomarker, her2.
Shares HER2 IHC 2+ (equivocal, reflex to ISH), HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), HER2 IHC 3+ (HER2-positive by immunohistochemistry), FISH / ISH (in situ hybridisation) and the tags biomarker, her2.
Shares HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), HER2 IHC 3+ (HER2-positive by immunohistochemistry), Trastuzumab deruxtecan, HER2 and the tags biomarker, her2.
Shares HER2 IHC and ISH companion assays (HercepTest, PATHWAY 4B5, HER2 Dual ISH), HER2 IHC 3+ (HER2-positive by immunohistochemistry), Trastuzumab deruxtecan, HER2 and the tags biomarker, her2.
Shares Gene amplification and copy-number change, FISH / ISH (in situ hybridisation) and the tag biomarker.
Shares Trastuzumab emtansine, Trastuzumab deruxtecan, HER2, HER2-positive breast cancer and the tag her2.
Shares HER2 (ERBB2) activating mutation, HER2 and the tag biomarker.
Shares Biliary tract cancer (all types), Gallbladder cancer, Colorectal cancer and the tag biomarker.