title: Progression of abnormal MIB-1 staining patterns of reserve cells in cervical smears from women ultimately developing high grade squamous intraepithelial lesions.
abstract: OBJECTIVE
  To assess, in a longitudinal study in women diagnosed with high grade squamous epithelial lesion (HSIL), the progression over time of proliferative activity in reserve cells using population screening cervical cytology specimens.
  
  
  METHODS
  Twenty consecutive, unselected patients with HSIL lesions were part of the national cervical screening program. From the archives, for each patient, the last prior normal population screening smear was included in the study. Concurrent sets of cervical smears from 80 age-matched women without pathology formed the controls. The original slides were stained using MIB-1 monoclonal antibody. The fraction of MIB-1-positive reserve cells was assessed using systematic random sampling and running progressive means assessment to ensure a sufficient sample size.
  
  
  RESULTS
  The proliferation fraction in reserve cells of HSIL patients was significantly raised (mean, 65.0%; range, 53.5-94.1%; p < 0.01) as compared with that in concurrent controls (mean, 12.8%; range, 1.9-45.4%). Prior smears from HSIL patients, although without morphologic abnormalities, had abnormally high proliferation fractions (mean, 59.1%; range, 1.0-94.7%), significantly raised over those from concurrent controls (mean, 9.4%; range
  
  
  CONCLUSIONS
  In population-based cervical smear screening, HSIL patients already have abnormally raised proliferation fractions of reserve cells, even without morphologic changes in squamous cells, 1-5 (mean, 3.6) years prior to diagnosis.
authors.affiliation: Department of Obstetrics and Gynaecology, Reinier de Graaf Gasthuis, Delft, The Netherlands. f.c.siemens@lcpl.nl
authors.forename: Frederike C
authors.initials: FC
authors.lastname: Siemens
authors.forename: Carolien
authors.initials: C
authors.lastname: van Haaften
authors.forename: Johan C
authors.initials: JC
authors.lastname: Kuijpers
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Helmerhorst
authors.forename: Mathilde E
authors.initials: ME
authors.lastname: Boon
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002452:Cell Count; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000737:chemistry* / Q000473:pathology; D002584:Cervix Uteri / Q000737:chemistry / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis*; D015588:Observer Variation; D011379:Prognosis; D015203:Reproducibility of Results; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000473:pathology; D014626:Vaginal Smears; D002578:Uterine Cervical Dysplasia / Q000737:chemistry* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen