Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Oncology, HER2, colorectal cancer, EGFR-targeted therapy, fluorescence in situ hybridisation, IN-SITU HYBRIDIZATION, CELL LUNG-CANCER, FACTOR RECEPTOR EGFR, CETUXIMAB, FISH, PREDICTS, KRAS, CHEMOTHERAPY, PANITUMUMAB, GUIDELINES, Adenocarcinoma, Adult, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Cetuximab, Colorectal Neoplasms, Female, Follow-Up Studies, Gene Amplification, Gene Dosage, Gene Expression Regulation, Neoplastic, Humans, In Situ Hybridization, Fluorescence, Male, Middle Aged, Mutation, Panitumumab, Prognosis, Proto-Oncogene Proteins, Proto-Oncogene Proteins p21(ras), Receptor, ErbB-2, Retrospective Studies, Survival Rate, ras Proteins, Receptor, erbB-2, 1112 Oncology and Carcinogenesis, 1117 Public Health and Health Services, Oncology & Carcinogenesis, 3211 Oncology and carcinogenesis

Abstract:

Background:In metastatic colorectal cancer (mCRC), KRAS is the only validated biomarker used to select patients for administration of epidermal growth factor receptor (EGFR)-targeted therapies. To identify additional predictive markers, we investigated the importance of HER2, the primary EGFR dimerisation partner, in this particular disease.Methods:We evaluated the HER2 gene status by fluorescence in situ hybridisation (FISH) in 170 KRAS wild-type mCRC patients treated with cetuximab or panitumumab.Results:Depending on HER2 gene copy number status, patients showed three distinct cytogenetic profiles: 4% of patients had HER2 gene amplification (R:HER2/CEP172) in all neoplastic cells (HER2-all-A), 61% of patients had HER2 gain due to polysomy or to gene amplification in minor clones (HER2-FISH+*), and 35% of patients had no or slight HER2 gain (HER2-FISH-). These subgroups were significantly correlated with different clinical behaviours, in terms of response rate (RR; P=0.0006), progression-free survival (PFS; P<0.0001) and overall survival (OS; P<0.0001). Patients with HER2-all-A profile experienced the worst outcome, patients with HER2-FISH- profile showed an intermediate behaviour and patients with HER2-FISH+* profile were related to the highest survival probability (median PFS in months: 2.5 vs 3.9 vs 7.6, respectively; median OS in months: 4.2 vs 9.7 vs 13, respectively).Conclusion:HER2 gene copy number status may influence the clinical response to anti-EGFR-targeted therapy in mCRC patients.