{"entity":{"id":"heracles-criteria","kind":"term","name":"HERACLES criteria (HER2 in bowel cancer)","aka":["HERACLES diagnostic criteria","HER2 scoring in colorectal cancer","colorectal HER2 criteria","ERBB2 positivity colorectal"],"tldr":"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).\n\nWhat 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.\n\nWhy 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.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/HER2/neu","links":[{"label":"Valtorta, Mod Pathol 2015: assessment of a HER2 scoring system for colorectal cancer, the HERACLES diagnostic criteria (256 and 830 tumours)","url":"https://doi.org/10.1038/modpathol.2015.98"},{"label":"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)","url":"https://www.nice.org.uk/guidance/ng151/chapter/Recommendations"}],"tags":["gi","colorectal"],"related":[],"cancers":["colorectal","her2-amplified-colorectal","colon-cancer","rectal-cancer"],"sections":[],"technologies":["histopathology-ihc","cgp"],"targets":["her2"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["extended-ras-testing","sidedness","tumour-grade"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/heracles-criteria/","neighbours":{"cancer":[{"id":"colon-cancer","kind":"cancer","name":"Colon cancer (adenocarcinoma of the colon)","route":"/cancers/colon-cancer/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"her2-amplified-colorectal","kind":"cancer","name":"HER2-amplified colorectal cancer","route":"/cancers/her2-amplified-colorectal/"},{"id":"rectal-cancer","kind":"cancer","name":"Rectal cancer","route":"/cancers/rectal-cancer/"}],"technology":[{"id":"cgp","kind":"technology","name":"Comprehensive genomic profiling","route":"/technologies/cgp/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"target":[{"id":"her2","kind":"target","name":"HER2","route":"/targets/her2/"}],"term":[{"id":"extended-ras-testing","kind":"term","name":"Extended RAS testing","route":"/terms/extended-ras-testing/"},{"id":"tumour-grade","kind":"term","name":"Grade","route":"/terms/tumour-grade/"},{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"}]}}