title: Distribution of the c-MYC gene product in colorectal neoplasia.
abstract: OBJECTIVE
  Recent attempts to study MYC distribution in human samples have been confounded by a lack of agreement in immunohistochemical staining between antibodies targeting the N-terminus and those targeting the C-terminus of the MYC protein. The aim of this study was to use a novel in-situ hybridization (ISH) approach to detect MYC mRNA in clinically relevant samples, and thereby determine the reliability of MYC-targeting antibodies.
  
  
  RESULTS
  We performed immunohistochemistry on human formalin-fixed paraffin embedded normal colon (n = 15), hyperplastic polyp (n = 4) and neoplastic colon samples (n = 55), using the N-terminally directed antibody Y69, and the C-terminally directed antibody 9E10. The MYC protein distributions were then compared with the location of MYC mRNA, determined by ISH. We found that the localization of MYC mRNA correlated well with the protein distribution determined with the N-terminally directed antibody Y69, and was also associated with expression of the proliferation marker Ki67. The protein distribution determined with the C-terminally directed antibody 9E10 was not always associated with MYC mRNA, Y69, or Ki67, and indeed often showed a reciprocal pattern of expression, with staining being strongest in non-proliferating cells.
  
  
  CONCLUSIONS
  The observed discrepancy between the staining patterns suggests that the significance of 9E10 in immunohistochemical staining is currently uncertain, and therefore should be interpreted with caution.
authors.affiliation: Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Baker
authors.affiliation: Department of Histopathology, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Van Noorden
authors.affiliation: Department of Histopathology, University College London, London, UK.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodriguez-Justo
authors.affiliation: Department of Cellular Pathology, Clarence Memorial Wing, St Mary's Hospital, London, UK.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cohen
authors.affiliation: Centre for Tumour Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Wright
authors.affiliation: Department of Histopathology, West Middlesex University Hospital, Isleworth, UK.
authors.forename: Irvin A
authors.initials: IA
authors.lastname: Lampert
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000911:Antibodies, Monoclonal; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D003111:Colonic Polyps / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D000911:Antibodies, Monoclonal; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger
keywords: c-MYC; colorectal cancer; immunohistochemistry; in-situ hybridization
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