title: The value of immunohistochemical determination of topoisomerase IIα and Ki67 as markers of cell proliferation and malignant transformation in colonic mucosa.
abstract: BACKGROUND
  Considering the role of topoisomerase IIα in cell division, and its increased expression in the G2/M phase of cell cycle, immunohistochemical staining for topoisomerase IIα might be used as a marker for cell proliferation or malignant transformation and compared with traditional proliferation marker (Ki67).
  
  
  METHODS
  In this study, 215 consecutive patients, who had undergone colonoscopy with biopsy, were included. The biopsy samples were fixed in formaldehyde, embedded in paraffin, cut into 3- to 4-μm sections, stained with hematoxylin-eosin and analyzed under a light microscope for pathologic diagnosis. For determination of topoisomerase IIα and Ki67 expression, paraffin blocks were cut into 4- to 5-μm sections and immunohistochemically stained with antitopoisomerase IIα antibody and Ki67. The dysplasia level was determined in adenomas and inflammatory bowel disease (IBD) samples using standard histologic criteria, whereas the grade of differentiation was determined for all colonic carcinomas.
  
  
  RESULTS
  In 27 patients (12.6%) normal colonic mucosa was found, IBD was diagnosed in 72 patients (33.5%), 68 (31.6%) patients had adenomas, and 48 (22.3%) were diagnosed as colon carcinoma. In all samples with epithelial dysplasia, higher topoisomerase IIα expression was related to a higher level of dysplasia grade (P<0.0001). High topoisomerase IIα expression was found in all samples of colorectal carcinomas (low and high grade). There was strong correlation between topoisomerase IIα and Ki67 expression in all levels of epithelial dysplasia as well as tumor grades.
  
  
  CONCLUSIONS
  The imunohistochemical staining for topoisomerase IIα expression might be useful as additional marker for mucosal dysplasia degree determination, as well as in differentiation of reactive/repair changes from dysplasia in IBD patients, but these findings need further evaluation.
authors.affiliation: Departments of *Internal Medicine, Division of Gastroenterology and Hepatology †Pathology, University Hospital Zagreb, Zagreb, Croatia.
authors.forename: Ivana Knezevic
authors.initials: IK
authors.lastname: Stromar
authors.forename: Jasminka
authors.initials: J
authors.lastname: Jakic-Razumovic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D002454:Cell Differentiation; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D016195:G2 Phase; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D019394:Ki-67 Antigen / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D004250:DNA Topoisomerases, Type II