# HERACLES criteria (HER2 in bowel cancer)

Source: https://onco.cc/terms/heracles-criteria/  
OnCo record `heracles-criteria` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Bowel cancer needed its own rule for calling a tumour HER2-positive, because the rules written for breast and stomach cancer did not transfer. The HERACLES criteria are that rule: intense membrane staining in more than half the cells, confirmed by gene amplification, which finds about one in twenty RAS wild-type bowel cancers.

## Summary

Why a separate rule. HER2-directed drugs work in colorectal cancer only in a small, well-defined group, and enrolling the wrong patients would have buried the effect. A consensus panel of pathologists adapted the breast and gastric protocols for colorectal tissue on an archival cohort of 256 tumours, then applied the result prospectively to screen 830 KRAS wild-type tumours for the HERACLES phase 2 trial of trastuzumab and lapatinib (Valtorta 2015).

What the criteria say. A positive tumour shows intense membranous HER2 protein expression, corresponding to homogeneous gene amplification, in more than 50 percent of cells. No tumour scoring 0 or 1+ by immunohistochemistry was amplified, and concordance between silver and fluorescence in situ hybridisation was complete. In both the archival and the clinical cohorts about 5 percent of KRAS wild-type colorectal cancers met the definition.

Why it matters beyond pathology. In a population resistant to cetuximab, HER2 positivity defined this way predicted response to HER2-directed therapy, which is how a scoring rule became a predictive biomarker. The criteria are why the reported prevalence of HER2 amplification in colorectal cancer clusters around 3 to 5 percent rather than the higher figures quoted when breast cancer rules are applied, and they are the reason the parent record's HER2 rows and the HER2-amplified colorectal page test RAS wild-type tumours specifically.

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: HERACLES diagnostic criteria; HER2 scoring in colorectal cancer; colorectal HER2 criteria; ERBB2 positivity colorectal
- Tags: gi; colorectal

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/HER2/neu
- Valtorta, Mod Pathol 2015: assessment of a HER2 scoring system for colorectal cancer, the HERACLES diagnostic criteria (256 and 830 tumours): https://doi.org/10.1038/modpathol.2015.98
- NICE NG151: colorectal cancer, recommendations (Lynch 1.1, local disease 1.3, biomarkers 1.4, metastatic disease 1.5, ongoing care and support including follow-up 1.6): https://www.nice.org.uk/guidance/ng151/chapter/Recommendations

## Connected records

- cancers: [Colon cancer (adenocarcinoma of the colon)](https://onco.cc/cancers/colon-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [HER2-amplified colorectal cancer](https://onco.cc/cancers/her2-amplified-colorectal/), [Rectal cancer](https://onco.cc/cancers/rectal-cancer/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [HER2](https://onco.cc/targets/her2/)
- terms: [Extended RAS testing](https://onco.cc/terms/extended-ras-testing/), [Grade](https://onco.cc/terms/tumour-grade/), [Sidedness (left vs right colon)](https://onco.cc/terms/sidedness/)

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