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RESEARCH PRODUCT
EGFR gene copy number decreases during anti-EGFR antibody therapy in colorectal cancer
Eva-maria BirkmanEva-maria BirkmanJari SundströmJari SundströmOlli CarpénOlli CarpénLaura LahtinenTeijo KuopioAnnika ÅLgarsAnnika ÅLgarsEija KorkeilaRaija RistamäkiMinnamaija LintunenTuulia AvorantaTuulia Avorantasubject
Male0301 basic medicineTime FactorsColorectal cancerBLOCKADEGene DosageCetuximabmedicine.disease_causeAntineoplastic Agents Immunological0302 clinical medicinePREDICTS RESPONSEMedicineHETEROGENEITYBENEFITCopy-number variationEpidermal growth factor receptorIn Situ Hybridization FluorescenceAged 80 and overbiologyPanitumumabvasta-aineetMiddle AgedImmunohistochemistry3. Good healthErbB ReceptorsGene Expression Regulation NeoplasticTreatment OutcomeRAS MUTATIONSChemotherapy Adjuvant030220 oncology & carcinogenesisFemaleKRASAntibodyColorectal NeoplasmsAdultgene copy numbermedicine.drug_classCETUXIMAB THERAPY3122 Cancerssilver in situ hybridizationDown-Regulationcolorectal cancerIn situ hybridizationAdenocarcinomaMonoclonal antibodyta3111Pathology and Forensic MedicineProto-Oncogene Proteins p21(ras)03 medical and health sciencesKRASHumansWILD-TYPEMETAANALYSISAgedRetrospective Studiessyöpähoidotbusiness.industrymedicine.diseaseta3122Blockadeperäsuolisyöpä030104 developmental biologymonoclonal antibodyMutationCancer researchbiology.protein3111 BiomedicineNeoplasm Recurrence Localbusinessepidermal growth factor receptorACQUIRED-RESISTANCEdescription
Epidermal growth factor receptor (EGFR) gene copy number (GCN) increase is associated with a favorable anti-EGFR antibody treatment response in RAS wild-type metastatic colorectal cancer. However, there are limited and comparative data regarding the EGFR GCN in primary colorectal cancer tumors and corresponding metastases or the effect of anti-EGFR antibody treatment on EGFR GCN in recurrent disease. In addition, little is known about the potential EGFR GCN changes during anti-EGFR therapy in comparison with other treatment regimens. EGFR GCN was analyzed by EGFR immunohistochemistry-guided silver in situ hybridization in primary and corresponding recurrent local or metastatic tumors from 80 colorectal cancer patients. GCN levels were compared between KRAS wild-type patients having received antiEGFR therapy and patients having received other forms of treatment after primary surgery. The EGFR GCN decrease between primary and recurrent tumors was more pronounced among the anti EGFR-treated patients than among patients not treated with anti-EGFR therapy (P=.047). None of the patients experiencing an EGFR GCN increase of at least 1.0 between the primary and recurrent tumors were treated with antiEGFR antibodies. When including only patients with distant metastases, an EGFR GCN decrease of at least 1.0 was more common among the anti EGFR-treated patients than among patients not treated with anti-EGFR therapy (P=.028). Our results suggest that anti-EGFR antibody treatment is associated with EGFR GCN decrease between the primary and recurrent colorectal adenocarcinomas, whereas no GCN change is observed among patients receiving other forms of treatment after primary surgery. (C) 2018 The Authors. Published by Elsevier Inc. Peer reviewed
year | journal | country | edition | language |
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2018-12-01 | Human Pathology |