# 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

Source: https://onco.cc/key-papers/paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016/  
OnCo record `paper-richman-her2-amplification-quasar-focus-piccolo-j-pathol-2016` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Staining more than three thousand tumours from three British trials put a number on how often bowel cancer is HER2-driven: about 1% at stage II-III and 2% at stage IV, rising to 5% in the tumours with no RAS or BRAF mutation.

## Summary

HER2 amplification and overexpression were assessed in stage II-III and stage IV colorectal cancer patients, with the relationship to KRAS and BRAF status and outcome. Pathological material came from 1,914 patients in the QUASAR stage II-III trial and 1,342 patients in the FOCUS and PICCOLO stage IV trials, with tissue microarrays for HER2 immunohistochemistry, fluorescence in situ hybridisation and copy number for amplification, and pyrosequencing for KRAS and BRAF. HER2 protein overexpression was seen in 29 of 1,342 (2.2%) stage IV and 25 of 1,914 (1.3%) stage II-III tumours. Of the overexpressing cases, 27 of 28 stage IV and 20 of 24 stage II-III were amplified by fluorescence in situ hybridisation, and 41 of 47 showed copy number gains. Overexpression was associated with KRAS and BRAF wild-type status at all stages: 5.2% against 1.0% in stage IV and 2.1% against 0.2% in stage II-III. HER2 status was not associated with overall or progression-free survival, and at stage II-III there was no correlation with response to fluorouracil.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Journal of Pathology
- Year: 2016
- DOI: 10.1002/path.4679
- Authors: Richman SD, Southward K, Chambers P, et al.
- Findings: HER2 overexpression in 2.2% of stage IV and 1.3% of stage II-III patients.; 5.2% of KRAS and BRAF wild-type stage IV tumours against 1.0% of mutant ones.; Overexpression almost always confirmed as amplification (27 of 28 stage IV cases).
- What it means: 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.
- Caveats: Tissue microarrays can miss heterogeneous expression.; Predates the colorectal-specific HERACLES scoring criteria.; Trial populations rather than a consecutive series.

## Sources

- Richman et al., J Pathol 2016: HER2 amplification in 3,256 patients from QUASAR, FOCUS and PICCOLO: https://doi.org/10.1002/path.4679
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26690310/

## Connected records

- biomarkers: [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/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- technologies: [Cytogenetics and FISH](https://onco.cc/technologies/cytogenetics-fish/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [BRAF](https://onco.cc/targets/braf/), [HER2](https://onco.cc/targets/her2/), [KRAS](https://onco.cc/targets/kras/)
- institutions: [Leeds Cancer Centre, St James's University Hospital](https://onco.cc/institutions/leeds-cancer-centre/)
- terms: [FISH / ISH (in situ hybridisation)](https://onco.cc/terms/fish/), [Immunohistochemistry (IHC)](https://onco.cc/terms/ihc/), [Wild-type (WT)](https://onco.cc/terms/wild-type/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)
- trials: [HERACLES](https://onco.cc/trials/heracles/), [MOUNTAINEER](https://onco.cc/trials/mountaineer/)
- drugs: [Tucatinib](https://onco.cc/drugs/tucatinib/)

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