Assessment of a HER2 scoring system for colorectal cancer: results from a validation study

Abstract

We sought to develop criteria for ERBB2-positivity (HER2) in colorectal cancer to ensure accurate identification of ERBB2-amplified metastatic colorectal cancer patients suitable for enrolment in a phase II trial of ERBB2-targeted therapy (HERACLES trial). A two-step approach was used. In step 1, a consensus panel of pathologists adapted existing protocols for use in colorectal cancer to test ERBB2 expression and amplification. Collegial revision of an archival test cohort of colorectal cancer samples led to specific recommendations for adapting current breast and gastric cancer criteria for scoring ERBB2 in colorectal cancer. In step 2, from September 2012 to January 2015, colorectal-specific ERBB2 testing protocols and ERBB2 scoring criteria were used to centrally screen for ERBB2-positive KRAS wild-type colorectal cancer patients to be enrolled in the HERACLES trial (clinical validation cohort). In both archival test (N = 256) and clinical validation (N = 830) cohorts, a clinically sizeable 5% fraction of KRAS wild-type colorectal cancer patients was found to be ERBB2-positive according to the colorectal cancer-specific ERBB2 scoring criteria. ERBB2-positive tumors showed ERBB2 immunostaining consisting of intense membranous ERBB2 protein expression, corresponding to homogenous ERBB2 amplification, in 450% of cells. None of the immunohistochemistry 0 or 1+ cases was amplified. Concordance between SISH and FISH was 100%. In conclusion, we propose specific criteria for defining ERBB2-positivity in colorectal cancer (HERACLES Diagnostic Criteria). In a phase II trial of trastuzumab and lapatinib in a cetuximabresistant population, HERACLES Diagnostic Criteria shaped the selection of patients and defined ERBB2 as a predictive marker for response to ERBB2-targeted therapy in metastatic colorectal cancer.

Metabolic Signature on 18F-FDG PET/CT, HER2 Status, and Survival in Gastric Adenocarcinomas

“…This may be due to several preanalytical variables, such as the antibody used for immunohistochemistry. Although, the performance of the Dako HercepTest A0485 antibody seems comparable with the Ventana 4B5 (32), a recent study that directly compared results of these antibodies showed a slightly better performance with the Ventana system (33). For the purposes of this investigation, increased specificity allows us to be confident that our HER21 cases are truly HER2-overexpressing at the molecular/genetic level.…”

S3-Leitlinie – Kolorektales Karzinom

“…Der Nachweis einer HER2-neu Amplifikation/Überexpression hat zum gegenwärtigen Zeitpunkt keinen gesicherten Stellenwert in der Wahl der Erstlinientherapie [1069]. Allerdings liegen erste Daten vor, welche darauf hinweisen, dass eine HER2-neu Amplifikation mit einer Resistenz gegen anti-EGFR Substanzen verbunden sein kann [1070,1071].…”

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology

“…HER2 is rarely overexpressed in CRC (approximately 3% overall), but the prevalence is higher in RAS/BRAF wild-type tumors (reported at 5%-14%). 177,178 Specific molecular diagnostic methods have been proposed for HER2 testing in CRC, 179 and various therapeutic approaches are being tested in patients with tumors that have HER2 overexpression (eg, trastuzumab plus lapatinib, trastuzumab plus pertuzumab). 177,180 These approaches are currently considered investigational, and enrollment in a clinical trial is encouraged.…”