Influence of mRNA expression of epiregulin and amphiregulin on outcome of patients with metastatic colorectal cancer treated with 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as first-line treatment (FIRE 1-trial).
Our aim was to investigate the impact of EREG and AREG mRNA expression (by RT-qPCR) in patients with metastatic colorectal cancer (mCRC). In addition, epidermal growth factor receptor (EGFR) expression (by immunohistochemistry) as well as RAS-and PIK3CA-mutations (by pyrosequencing) were assessed. Tumors of 208 mCRC patients receiving 5-fluorouracil/leucovorin plus irinotecan (FUFIRI) or irinotecan plus oxaliplatin (mIROX) within the FIRE-1 trial were analyzed for mutations. Molecular characteristics were correlated with response, progression-free survival (PFS), overall survival (OS). mRNA expression was evaluated using ROC-analysis in 192 tumors (AREG high n = 31 vs. low n = 161; EREG high n = 89 vs. low n = 103). High versus low AREG expression was associated with PFS of 10.0 versus 8.0 months (HR = 0.62, 95% CI: 0.402-0.940, p = 0.03) and OS of 24.6 versus 18.7 months (HR = 0.72, 95% CI: 0.476-1.078, p = 0.11). High versus low EREG expression correlated with prolonged PFS (9.4 vs. 6.8 months, HR = 0.62, 95% CI: 0.460-0.846, p = 0.002) and OS (25.8 vs. 15.5 months, HR = 0.48, 95% CI: 0.351-0.657, p < 0.001). The positive prognostic effect of high EREG expression was confirmed in a multivariate analysis and was neither affected by EGFR expression nor by mutations of RAS- and PIK3CA-genes. EREG expression appears as an independent prognostic marker in patients with mCRC receiving first-line irinotecan-based chemotherapy.
Department of Medicine III And Comprehensive Cancer Centre, University Hospital Grosshadern, University of Munich, Germany.|Institute of Pathology, University of Munich, Germany.
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Stahler
Department of Medicine III And Comprehensive Cancer Centre, University Hospital Grosshadern, University of Munich, Germany.|DKTK, German Cancer Consortium, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
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Heinemann
Department of Medicine III And Comprehensive Cancer Centre, University Hospital Grosshadern, University of Munich, Germany.
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Giessen-Jung
Institute of Medical Informatics, Biometry, and Epidemiology, University of Munich, Germany.
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Crispin
Department of Medicine III And Comprehensive Cancer Centre, University Hospital Grosshadern, University of Munich, Germany.
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Schalhorn
Department of Medicine III And Comprehensive Cancer Centre, University Hospital Grosshadern, University of Munich, Germany.|DKTK, German Cancer Consortium, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
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Stintzing
Klinikum St. Marien, Oncology, Amberg, Germany.
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Fischer von Weikersthal
Onkologische Praxis, Landshut, Germany.
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Vehling-Kaiser
Onkologische Schwerpunktpraxis in Kronach, Ambulantes Zentrum Für Hämatologie Und Onkologie, Kronach, Germany.
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Stauch
Klinikum Chemnitz, Chemnitz, Germany.
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Quietzsch
ClinAssess GmbH, Leverkusen, Germany.
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Held
Department of Medicine III And Comprehensive Cancer Centre, University Hospital Grosshadern, University of Munich, Germany.
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von Einem
Department of Medicine III And Comprehensive Cancer Centre, University Hospital Grosshadern, University of Munich, Germany.
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Holch
Institute of Pathology, University of Munich, Germany.|DKTK, German Cancer Consortium, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
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Neumann
Institute of Pathology, University of Munich, Germany.|DKTK, German Cancer Consortium, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
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Kirchner
Institute of Pathology, University of Munich, Germany.|DKTK, German Cancer Consortium, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
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Jung
Department of Medicine III And Comprehensive Cancer Centre, University Hospital Grosshadern, University of Munich, Germany.|DKTK, German Cancer Consortium, German Cancer Research Centre (DKFZ), Heidelberg, Germany.
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DP
Modest
D000328:Adult; D000368:Aged; D066258:Amphiregulin / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D066260:Epiregulin / Q000235:genetics*; D005260:Female; D011905:Genes, ras; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*
D066258:Amphiregulin; D066260:Epiregulin; D009944:Organoplatinum Compounds; D012333:RNA, Messenger; D000077150:Oxaliplatin; D000077146:Irinotecan; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D002166:Camptothecin
AREG; EREG; RAS; metastatic colorectal cancer