title: Evaluation of prospective, routine application of Ki-67 immunoquantitation in early CIN for assessment of short-term progression risk.
abstract: OBJECTIVE
  To prospectively validate, in early cervical intraepithelial neoplasia (CIN), routine assessment of a previously developed prognostic Ki-67 immunoquantitative progression-risk model.
  
  
  METHODS
  Two hundred sixty-six consecutive cervical biopsies taken for an abnormal cytologic smear were routinely diagnosed by experienced pathologists as CIN. Ki-67 immunoquantitation was performed routinely by 3 technicians blinded to clinical and pathologic information. Progression of CIN 1-2 to CIN 3 in histologic follow-up biopsies was used as the intermediate end point.
  
  
  RESULTS
  In 58 (22%) biopsies, technical shortcomings prevented Ki-67 immunoquantitation, and in 22 biopsies no follow-up was available. The routine diagnosis in the 186 remaining biopsies was CIN 1 = 24, CIN 2 = 56 and CIN 3 = 106. In 52 marker biopsies with expert review diagnosis of CIN 1-2 and adequate follow-up, histologic biopsies revealed CIN 3 in 9 (17%) cases: 9 of 34 (26%) of Ki-67 high-risk and 0 of 18 (0%) of Ki-67 low-risk lesions (log rank = 5.0, P = .03). Routine CIN grade (1 or 2) was not prognostic (P = .65). Eleven (55%) of 20 CIN 1 and 7 of 32 (22%) CIN 2 cases were Ki-67 low risk and none progressed, contrasting with 4 of 9 (44%) progressions of Ki-67 high risk CIN 1s and 5 of 25 (20%) high risk CIN 2s. Expert CIN grades were stronger prognostically than routine CIN grade, but Ki-67 was still stronger.
  
  
  CONCLUSIONS
  Routine Ki-67 immunoquantitative progression prediction in CIN 1-2 is more predictive of CIN 3 in follow-up than are routine and review CIN grades.
authors.affiliation: Department of Pathology, Rogaland Central Hospital, P.O. Box 8100, 4068 Stavanger, Norway. baja@sir.no
authors.forename: Amold-Jan
authors.initials: AJ
authors.lastname: Kruse
authors.forename: Einar
authors.initials: E
authors.lastname: Gudlaugsson
authors.forename: Tove
authors.initials: T
authors.lastname: Helliesen
authors.forename: Emiel A
authors.initials: EA
authors.lastname: Janssen
authors.forename: Bianca
authors.initials: B
authors.lastname: van Diermen
authors.forename: Silje
authors.initials: S
authors.lastname: Sandvik
authors.forename: Jan P
authors.initials: JP
authors.lastname: Baak
mesh_terms: D001706:Biopsy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis* / Q000276:immunology*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D019394:Ki-67 Antigen