Heterogeneous EGFR gene copy number increase is common in colorectal cancer and defines response to anti-EGFR therapy
Anti-EGFR therapy is commonly used to treat colorectal cancer (CRC), although only a subset of patients benefit from the treatment. While KRAS mutation predicts non-responsiveness, positive predictive markers are not in clinical practice. We previously showed that immunohistochemistry (IHC)-guided E...
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Published in | PloS one Vol. 9; no. 6; p. e99590 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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18.06.2014
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Abstract | Anti-EGFR therapy is commonly used to treat colorectal cancer (CRC), although only a subset of patients benefit from the treatment. While KRAS mutation predicts non-responsiveness, positive predictive markers are not in clinical practice. We previously showed that immunohistochemistry (IHC)-guided EGFR gene copy number (GCN) analysis may identify CRC patients benefiting from anti-EGFR treatment. Here we tested the predictive value of such analysis in chemorefractory metastatic CRC, elucidated EGFR GCN heterogeneity within the tumors, and evaluated the association between EGFR GCN, KRAS status, and anti-EGFR antibody response in CRC cell lines. The chemorefractory patient cohort consisted of 54 KRAS wild-type (WT) metastatic CRC patients. EGFR GCN status was analyzed by silver in situ hybridization using a cut-off value of 4.0 EGFR gene copies/cell. KRAS-WT and KRAS mutant CRC cell lines with different EGFR GCN were used in in vitro studies. The chemorefractory CRC tumors with EGFR GCN increase (≥4.0) responded better to anti-EGFR therapy than EGFR GCN (<4.0) tumors (clinical benefit, P = 0.0004; PFS, HR = 0.23, 95% CI 0.12-0.46). EGFR GCN counted using EGFR IHC guidance was significantly higher than the value from randomly selected areas verifying intratumoral EGFR GCN heterogeneity. In CRC cell lines, EGFR GCN correlated with EGFR expression. Best anti-EGFR response was seen with KRAS-WT, EGFR GCN = 4 cells and poorest response with KRAS-WT, EGFR GCN = 2 cells. Anti-EGFR response was associated with AKT and ERK1/2 phosphorylation, which was effectively inhibited only in cells with KRAS-WT and increased EGFR GCN. In conclusion, IHC-guided EGFR GCN is a promising predictor of anti-EGFR treatment efficacy in chemorefractory CRC. |
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AbstractList | Anti-EGFR therapy is commonly used to treat colorectal cancer (CRC), although only a subset of patients benefit from the treatment. While KRAS mutation predicts non-responsiveness, positive predictive markers are not in clinical practice. We previously showed that immunohistochemistry (IHC)-guided EGFR gene copy number (GCN) analysis may identify CRC patients benefiting from anti-EGFR treatment. Here we tested the predictive value of such analysis in chemorefractory metastatic CRC, elucidated EGFR GCN heterogeneity within the tumors, and evaluated the association between EGFR GCN, KRAS status, and anti-EGFR antibody response in CRC cell lines. The chemorefractory patient cohort consisted of 54 KRAS wild-type (WT) metastatic CRC patients. EGFR GCN status was analyzed by silver in situ hybridization using a cut-off value of 4.0 EGFR gene copies/cell. KRAS-WT and KRAS mutant CRC cell lines with different EGFR GCN were used in in vitro studies. The chemorefractory CRC tumors with EGFR GCN increase (≥4.0) responded better to anti-EGFR therapy than EGFR GCN (<4.0) tumors (clinical benefit, P = 0.0004; PFS, HR = 0.23, 95% CI 0.12–0.46). EGFR GCN counted using EGFR IHC guidance was significantly higher than the value from randomly selected areas verifying intratumoral EGFR GCN heterogeneity. In CRC cell lines, EGFR GCN correlated with EGFR expression. Best anti-EGFR response was seen with KRAS-WT, EGFR GCN = 4 cells and poorest response with KRAS-WT, EGFR GCN = 2 cells. Anti-EGFR response was associated with AKT and ERK1/2 phosphorylation, which was effectively inhibited only in cells with KRAS-WT and increased EGFR GCN. In conclusion, IHC-guided EGFR GCN is a promising predictor of anti-EGFR treatment efficacy in chemorefractory CRC. Anti-EGFR therapy is commonly used to treat colorectal cancer (CRC), although only a subset of patients benefit from the treatment. While KRAS mutation predicts non-responsiveness, positive predictive markers are not in clinical practice. We previously showed that immunohistochemistry (IHC)-guided EGFR gene copy number (GCN) analysis may identify CRC patients benefiting from anti-EGFR treatment. Here we tested the predictive value of such analysis in chemorefractory metastatic CRC, elucidated EGFR GCN heterogeneity within the tumors, and evaluated the association between EGFR GCN, KRAS status, and anti-EGFR antibody response in CRC cell lines. The chemorefractory patient cohort consisted of 54 KRAS wild-type (WT) metastatic CRC patients. EGFR GCN status was analyzed by silver in situ hybridization using a cut-off value of 4.0 EGFR gene copies/cell. KRAS -WT and KRAS mutant CRC cell lines with different EGFR GCN were used in in vitro studies. The chemorefractory CRC tumors with EGFR GCN increase (≥4.0) responded better to anti-EGFR therapy than EGFR GCN (<4.0) tumors (clinical benefit, P = 0.0004; PFS, HR = 0.23, 95% CI 0.12–0.46). EGFR GCN counted using EGFR IHC guidance was significantly higher than the value from randomly selected areas verifying intratumoral EGFR GCN heterogeneity. In CRC cell lines, EGFR GCN correlated with EGFR expression. Best anti-EGFR response was seen with KRAS -WT, EGFR GCN = 4 cells and poorest response with KRAS -WT, EGFR GCN = 2 cells. Anti-EGFR response was associated with AKT and ERK1/2 phosphorylation, which was effectively inhibited only in cells with KRAS -WT and increased EGFR GCN. In conclusion, IHC-guided EGFR GCN is a promising predictor of anti-EGFR treatment efficacy in chemorefractory CRC. |
Author | Sundström, Jari Avoranta, Tuulia Jokilehto, Terhi Ristimäki, Ari Österlund, Pia Carpén, Olli Ålgars, Annika Ristamäki, Raija Lintunen, Minnamaija |
AuthorAffiliation | 7 Department of Pathology, Haartman Institute and Genome-Scale Biology, Research Programs Unit, University of Helsinki, Helsinki, Finland 2 Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland 3 Department of Oncology, University of Helsinki, Helsinki, Finland The Chinese University of Hong Kong, Hong Kong 1 Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland 6 Division of Pathology and Genetics, Helsinki University Central Hospital - HUSLAB, Helsinki, Finland 4 Department of Pathology, University of Turku, Turku, Finland 5 Department of Pathology, Turku University Hospital –Tyks-Sapa, Turku, Finland |
AuthorAffiliation_xml | – name: 7 Department of Pathology, Haartman Institute and Genome-Scale Biology, Research Programs Unit, University of Helsinki, Helsinki, Finland – name: 2 Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland – name: The Chinese University of Hong Kong, Hong Kong – name: 4 Department of Pathology, University of Turku, Turku, Finland – name: 1 Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland – name: 3 Department of Oncology, University of Helsinki, Helsinki, Finland – name: 5 Department of Pathology, Turku University Hospital –Tyks-Sapa, Turku, Finland – name: 6 Division of Pathology and Genetics, Helsinki University Central Hospital - HUSLAB, Helsinki, Finland |
Author_xml | – sequence: 1 givenname: Annika surname: Ålgars fullname: Ålgars, Annika organization: Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland – sequence: 2 givenname: Tuulia surname: Avoranta fullname: Avoranta, Tuulia organization: Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland – sequence: 3 givenname: Pia surname: Österlund fullname: Österlund, Pia organization: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland; Department of Oncology, University of Helsinki, Helsinki, Finland – sequence: 4 givenname: Minnamaija surname: Lintunen fullname: Lintunen, Minnamaija organization: Department of Pathology, University of Turku, Turku, Finland; Department of Pathology, Turku University Hospital -Tyks-Sapa, Turku, Finland – sequence: 5 givenname: Jari surname: Sundström fullname: Sundström, Jari organization: Department of Pathology, University of Turku, Turku, Finland; Department of Pathology, Turku University Hospital -Tyks-Sapa, Turku, Finland – sequence: 6 givenname: Terhi surname: Jokilehto fullname: Jokilehto, Terhi organization: Department of Pathology, University of Turku, Turku, Finland; Department of Pathology, Turku University Hospital -Tyks-Sapa, Turku, Finland – sequence: 7 givenname: Ari surname: Ristimäki fullname: Ristimäki, Ari organization: Division of Pathology and Genetics, Helsinki University Central Hospital - HUSLAB, Helsinki, Finland; Department of Pathology, Haartman Institute and Genome-Scale Biology, Research Programs Unit, University of Helsinki, Helsinki, Finland – sequence: 8 givenname: Raija surname: Ristamäki fullname: Ristamäki, Raija organization: Department of Oncology and Radiotherapy, Turku University Hospital, Turku, Finland – sequence: 9 givenname: Olli surname: Carpén fullname: Carpén, Olli organization: Department of Pathology, University of Turku, Turku, Finland; Department of Pathology, Turku University Hospital -Tyks-Sapa, Turku, Finland |
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Cites_doi | 10.1093/annonc/mdi064 10.1038/nature11156 10.1038/onc.2012.302 10.1038/bjc.2011.223 10.1200/JCO.2007.11.5956 10.1186/1756-8722-2-18 10.1016/S1470-2045(05)70102-9 10.1097/CJI.0b013e31825943aa 10.1158/1078-0432.CCR-08-0449 10.1016/j.ejca.2008.10.026 10.1056/NEJMoa1113205 10.1016/S0305-7372(10)00036-8 10.1016/j.ejca.2010.03.005 10.1097/CJI.0000000000000004 10.1136/jclinpath-2011-200353 10.1016/j.ccr.2011.11.005 10.1002/ijc.23253 10.1038/modpathol.2011.198 10.1002/stem.1031 10.1158/0008-5472.CAN-06-0191 10.1186/1756-8722-5-52 10.1111/j.1365-2184.2012.00837.x |
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Copyright | 2014 Ålgars et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2014 Ålgars et al 2014 Ålgars et al |
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DocumentTitleAlternate | EGFR Gene Copy Number and Anti-EGFR Response in Colorectal Cancer |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: AÅ TA PÖ ML JS TJ AR RR OC. Performed the experiments: ML JS TJ. Analyzed the data: AÅ TA PÖ ML JS TJ AR RR OC. Contributed reagents/materials/analysis tools: AÅ TA PÖ ML JS TJ AR RR OC. Wrote the paper: AÅ TA PÖ ML JS TJ AR RR OC. Competing Interests: AÅ, ML, JS, RR and OC are inventors in a patent related to this work: US 20110217296 A1 Method for selecting patients for treatment with an EGFR inhibitor. All remaining authors have declared no conflicts of interest. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials. |
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References | 18794099 - Clin Cancer Res. 2008 Sep 15;14(18):5869-76 16618717 - Cancer Res. 2006 Apr 15;66(8):3992-5 22232074 - Stem Cells. 2012 Mar;30(3):363-71 17664472 - J Clin Oncol. 2007 Aug 1;25(22):3238-45 15668283 - Ann Oncol. 2005 Feb;16(2):273-8 24316553 - J Immunother. 2014 Jan;37(1):26-35 22397650 - N Engl J Med. 2012 Mar 8;366(10):883-92 22130903 - J Clin Pathol. 2012 Mar;65(3):218-23 22722830 - Nature. 2012 Jun 28;486(7404):532-6 15863375 - Lancet Oncol. 2005 May;6(5):279-86 22576349 - J Immunother. 2012 Jun;35(5):440-7 20399639 - Eur J Cancer. 2010 Jun;46(9):1703-11 20189053 - Cancer Treat Rev. 2010 Feb;36 Suppl 1:S1-10 22925500 - Cell Prolif. 2012 Oct;45(5):413-9 18033688 - Int J Cancer. 2008 Apr 1;122(7):1530-8 19386128 - J Hematol Oncol. 2009;2:18 22222640 - Mod Pathol. 2012 May;25(5):637-50 22797062 - Oncogene. 2013 Jun 6;32(23):2873-81 21694725 - Br J Cancer. 2011 Jul 12;105(2):255-62 22897982 - J Hematol Oncol. 2012;5:52 22137795 - Cancer Cell. 2011 Dec 13;20(6):810-7 19097774 - Eur J Cancer. 2009 Jan;45(2):228-47 A Lievre (ref2) 2006; 66 J Rüschoff (ref19) 2012; 25 Y Feng (ref21) 2012; 45 M Moroni (ref4) 2005; 6 DZ Chang (ref3) 2009; 2 EA Eisenhauer (ref10) 2009; 45 P Correale (ref12) 2010; 46 T Yoshida (ref22) 2008; 122 A Ålgars (ref8) 2011; 105 S Kasper (ref11) 2012; 32 M Gerlinger (ref15) 2012; 366 AG Vaiopoulos (ref20) 2012; 30 N Personeni (ref6) 2008; 14 S Misale (ref16) 2012; 486 ZY Yang (ref9) 2012; 5 M Tanner (ref18) 2005; 16 M Snuderl (ref17) 2011; 20 A Sartore-Bianchi (ref5) 2007; 25 A Sartore-Bianchi (ref7) 2012; 65 C Botta (ref13) 2012; 35 P Correale (ref14) 2014; 37 O Bouché (ref1) 2010; 36 |
References_xml | – volume: 16 start-page: 273 year: 2005 ident: ref18 article-title: Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab publication-title: Ann Oncol doi: 10.1093/annonc/mdi064 contributor: fullname: M Tanner – volume: 486 start-page: 532 year: 2012 ident: ref16 article-title: Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer publication-title: Nature doi: 10.1038/nature11156 contributor: fullname: S Misale – volume: 32 start-page: 2873 year: 2012 ident: ref11 article-title: Oncogenic RAS simultaneously protects against anti-EGFR antibody-dependent cellular cytotoxicity and EGFR signaling blockade publication-title: Oncogene doi: 10.1038/onc.2012.302 contributor: fullname: S Kasper – volume: 105 start-page: 255 year: 2011 ident: ref8 article-title: EGFR gene copy number assessment from areas with highest EGFR expression predicts response to anti-EGFR therapy in colorectal cancer publication-title: Br J Cancer doi: 10.1038/bjc.2011.223 contributor: fullname: A Ålgars – volume: 25 start-page: 3238 year: 2007 ident: ref5 article-title: Epidermal growth factor receptor gene copy number and clinical outcome of metastatic colorectal cancer treated with panitumumab publication-title: J Clin Oncol doi: 10.1200/JCO.2007.11.5956 contributor: fullname: A Sartore-Bianchi – volume: 2 start-page: 18 year: 2009 ident: ref3 article-title: Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy publication-title: J Hematol Oncol doi: 10.1186/1756-8722-2-18 contributor: fullname: DZ Chang – volume: 6 start-page: 279 year: 2005 ident: ref4 article-title: Gene copy number for epidermal growth factor receptor (EGFR) and clinical response to antiEGFR treatment in colorectal cancer: a cohort study publication-title: Lancet Oncol doi: 10.1016/S1470-2045(05)70102-9 contributor: fullname: M Moroni – volume: 35 start-page: 440 year: 2012 ident: ref13 article-title: Immune-modulating effects of the newest cetuximab-based chemoimmunotherapy regimen in advanced colorectal cancer patients publication-title: J Immunother doi: 10.1097/CJI.0b013e31825943aa contributor: fullname: C Botta – volume: 14 start-page: 5869 year: 2008 ident: ref6 article-title: Clinical usefulness of EGFR gene copy number as a predictive marker in colorectal cancer patients treated with cetuximab: a fluorescent in situ hybridization study publication-title: Clin Cancer Res doi: 10.1158/1078-0432.CCR-08-0449 contributor: fullname: N Personeni – volume: 45 start-page: 228 year: 2009 ident: ref10 article-title: New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) publication-title: Eur J Cancer doi: 10.1016/j.ejca.2008.10.026 contributor: fullname: EA Eisenhauer – volume: 366 start-page: 883 year: 2012 ident: ref15 article-title: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing publication-title: N Engl J Med doi: 10.1056/NEJMoa1113205 contributor: fullname: M Gerlinger – volume: 36 start-page: S1 year: 2010 ident: ref1 article-title: The role of anti-epidermal growth factor receptor monoclonal antibody monotherapy in the treatment of metastatic colorectal cancer publication-title: Cancer Treat Rev doi: 10.1016/S0305-7372(10)00036-8 contributor: fullname: O Bouché – volume: 46 start-page: 1703 year: 2010 ident: ref12 article-title: Cytotoxic drugs up-regulate epidermal growth factor receptor (EGFR) expression in colon cancer cells and enhance their susceptibility to EGFR-targeted antibody-dependent cell-mediated-cytotoxicity (ADCC) publication-title: Eur J Cancer doi: 10.1016/j.ejca.2010.03.005 contributor: fullname: P Correale – volume: 37 start-page: 26 year: 2014 ident: ref14 article-title: Gemcitabine, oxaliplatin, levofolinate, 5-fluorouracil, granulocyte-macrophage colony-stimulating factor, and interleukin-2 (GOLFIG) versus FOLFOX chemotherapy in metastatic colorectal cancer patients: the GOLFIG-2 multicentric open-label randomized phase III trial publication-title: J Immunother doi: 10.1097/CJI.0000000000000004 contributor: fullname: P Correale – volume: 65 start-page: 218 year: 2012 ident: ref7 article-title: Standardisation of EGFR FISH in colorectal cancer: results of an international interlaboratory reproducibility ring study publication-title: J Clin Pathol doi: 10.1136/jclinpath-2011-200353 contributor: fullname: A Sartore-Bianchi – volume: 20 start-page: 810 year: 2011 ident: ref17 article-title: Mosaic amplification of multiple receptor tyrosine kinase genes in glioblastoma publication-title: Cancer Cell doi: 10.1016/j.ccr.2011.11.005 contributor: fullname: M Snuderl – volume: 122 start-page: 1530 year: 2008 ident: ref22 article-title: Matuzumab and cetuximab activate the epidermal growth factor receptor but fail to trigger downstream signaling by Akt or Erk publication-title: Int J Cancer doi: 10.1002/ijc.23253 contributor: fullname: T Yoshida – volume: 25 start-page: 637 year: 2012 ident: ref19 article-title: HER2 testing in gastric cancer: a practical approach publication-title: Mod Pathol doi: 10.1038/modpathol.2011.198 contributor: fullname: J Rüschoff – volume: 30 start-page: 363 year: 2012 ident: ref20 article-title: Colorectal cancer stem cells publication-title: Stem Cells doi: 10.1002/stem.1031 contributor: fullname: AG Vaiopoulos – volume: 66 start-page: 3992 year: 2006 ident: ref2 article-title: KRAS mutation status is predictive of response to cetuximab therapy in colorectal cancer publication-title: Cancer Res doi: 10.1158/0008-5472.CAN-06-0191 contributor: fullname: A Lievre – volume: 5 start-page: 52 year: 2012 ident: ref9 article-title: EGFR gene copy number as a predictive biomarker for the treatment of metastatic colorectal cancer with anti-EGFR monoclonal antibodies: a meta-analysis publication-title: J Hematol Oncol doi: 10.1186/1756-8722-5-52 contributor: fullname: ZY Yang – volume: 45 start-page: 413 year: 2012 ident: ref21 article-title: EGF signalling pathway regulates colon cancer stem cell proliferation and apoptosis publication-title: Cell Prolif doi: 10.1111/j.1365-2184.2012.00837.x contributor: fullname: Y Feng |
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Snippet | Anti-EGFR therapy is commonly used to treat colorectal cancer (CRC), although only a subset of patients benefit from the treatment. While KRAS mutation... Anti-EGFR therapy is commonly used to treat colorectal cancer (CRC), although only a subset of patients benefit from the treatment. While KRAS mutation... |
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SubjectTerms | Adult Aged AKT protein Antibody response Biotechnology Cancer Cancer therapies Cell Line, Tumor Chemotherapy Cohort Studies Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - drug therapy Colorectal Neoplasms - genetics Copy number Cytotoxicity Disease-Free Survival Drug Resistance, Neoplasm Epidermal growth factor Epidermal growth factor receptors Extracellular signal-regulated kinase Female Gastric cancer Gene amplification Gene Dosage Gene Expression Regulation, Neoplastic Genetic Heterogeneity Heterogeneity Histology Humans Immunohistochemistry In Situ Hybridization K-Ras protein Kaplan-Meier Estimate Male Medical diagnosis Medical prognosis Medicine and Health Sciences Metastases Metastasis Middle Aged Mutation NMR Nuclear magnetic resonance Oncology Pathology Patients Phosphorylation Protein expression Proteins Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins p21(ras) Radiation therapy ras Proteins - genetics Receptor, Epidermal Growth Factor - antagonists & inhibitors Receptor, Epidermal Growth Factor - genetics Reproducibility of Results Rodents Silver Stem cells Studies Therapy Treatment Outcome Tumors |
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Title | Heterogeneous EGFR gene copy number increase is common in colorectal cancer and defines response to anti-EGFR therapy |
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