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Breast and stomach cancer HER2 scoring rules do not fit the bowel. This study wrote colorectal-specific criteria, tested them on more than a thousand samples, and produced the definition of HER2-positive that the trials have used ever since.
Criteria for ERBB2 (HER2) positivity in colorectal cancer were developed in two steps to allow accurate identification of amplified metastatic patients for the HERACLES trial. A consensus panel of pathologists first adapted existing breast and gastric protocols for colorectal use on an archival test cohort of 256 samples, producing specific recommendations for scoring. Those colorectal-specific protocols and criteria were then applied from September 2012 to January 2015 to centrally screen 830 KRAS wild-type patients for the trial. In both cohorts, 5% of KRAS wild-type patients were HER2-positive by the criteria. Positive tumours showed intense membranous HER2 protein expression corresponding to homogeneous amplification in more than 50% of cells; no immunohistochemistry 0 or 1+ case was amplified, and concordance between silver and fluorescence in situ hybridisation was 100%.
It is the threshold behind the colorectal HER2 approvals: the more-than-50% rule, rather than the 10% used in gastric cancer, is what a pathologist applies when a bowel cancer is called HER2-positive.
Shares HERACLES, MOUNTAINEER, Cytogenetics and FISH, HER2 ISH amplified (ERBB2 gene amplification).
Shares Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Andrea Sartore-Bianchi, Salvatore Siena, HERACLES.
Shares Gene amplification and copy-number change, MOUNTAINEER, HER2 ISH amplified (ERBB2 gene amplification), HER2 IHC 3+ (HER2-positive by immunohistochemistry).
Shares DESTINY-CRC02, Gene amplification and copy-number change, HER2 ISH amplified (ERBB2 gene amplification), HER2 IHC 3+ (HER2-positive by immunohistochemistry).
Shares Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Andrea Sartore-Bianchi, Salvatore Siena, Istituto di Candiolo IRCCS (FPO).
Shares DESTINY-CRC02, MOUNTAINEER, Tucatinib, Trastuzumab.
Shares HERACLES, Gene amplification and copy-number change, Istituto di Candiolo IRCCS (FPO), Trastuzumab.
Shares Gene amplification and copy-number change, HER2 ISH amplified (ERBB2 gene amplification), HER2 IHC 3+ (HER2-positive by immunohistochemistry), FISH / ISH (in situ hybridisation).