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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.
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.
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 HERACLES, MOUNTAINEER, Cytogenetics and FISH, HER2 ISH amplified (ERBB2 gene amplification).
Shares MOUNTAINEER, HER2 ISH amplified (ERBB2 gene amplification), HER2 IHC 3+ (HER2-positive by immunohistochemistry), Tucatinib.
Shares HER2 ISH amplified (ERBB2 gene amplification), HER2 IHC 3+ (HER2-positive by immunohistochemistry), FISH / ISH (in situ hybridisation), Immunohistochemistry (IHC).
Shares HER2 IHC 3+ (HER2-positive by immunohistochemistry), FISH / ISH (in situ hybridisation), Immunohistochemistry (IHC), HER2.
Shares HERACLES, Wild-type (WT), KRAS, HER2.
Shares HERACLES, HER2 ISH amplified (ERBB2 gene amplification), KRAS, HER2.
Shares HER2 ISH amplified (ERBB2 gene amplification), HER2 IHC 3+ (HER2-positive by immunohistochemistry), HER2, Colorectal cancer.
Shares HERACLES, MOUNTAINEER, HER2, Colorectal cancer.