title: Heterogeneity in proliferation markers in colorectal cancer.
abstract: BACKGROUND
  The intratumoral heterogeneity in different markers of proliferation, and the immunohistochemical overexpression of the p53 protein-a possible regulator of proliferation-have been investigated to only a minor extent in colorectal cancer. The evaluation of tumour biopsy samples, especially preoperatively, when multiple sampling is not always feasible, must be based upon markers being more or less homogeneously expressed.
  
  
  METHODS
  Three different DNA-labelling techniques were investigated in multiple biopsy samples (2-10, median 4) from 19 tumours obtained from 18 patients. Anti-bromodeoxyuridine and Ki-67 monoclonal antibodies were used to detect nuclei of proliferating cells in adjacent tumour sections. Adjacent tumour material was analysed by flow cytometry of propidium iodide labelled nuclei. In addition, overexpression of the p53 protein was detected using the monoclonal anti-p53 antibody DO-7
  
  
  RESULTS
  There was considerable intratumoral heterogeneity in the labelling indices. No correlation was found between overexpression of the p53 protein and markers for proliferation, as indicated by observations made using three different methods. In contrast, the staining for p53 protein was either homogeneously positive or negative.
  
  
  CONCLUSIONS
  The results indicate that analyses of proliferation in preoperatively obtained tumour biopsies are of limited value for prognostic prediction, or other purposes, in view of the extensive intratumoral heterogeneity shown with three different markers.
authors.affiliation: Department of Surgery, University Hospital University of Uppsala, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Kressner
authors.forename: G
authors.initials: G
authors.lastname: Lindmark
authors.forename: B
authors.initials: B
authors.lastname: Gerdin
authors.forename: L
authors.initials: L
authors.lastname: Pahlman
authors.forename: B
authors.initials: B
authors.lastname: Glimelius
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D000911:Antibodies, Monoclonal / Q000276:immunology; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D001973:Bromodeoxyuridine / Q000032:analysis; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000473:pathology*; D004261:DNA Replication; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000276:immunology; D009687:Nuclear Proteins / Q000032:analysis* / Q000276:immunology; D015203:Reproducibility of Results; D016037:Single-Blind Method; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; D001973:Bromodeoxyuridine