title: Ki67 expression in bronchial preneoplastic lesions and carcinoma in situ defined according to the new 1999 WHO/IASLC criteria: a preliminary study.
abstract: OBJECTIVE
  The World Health Organization classification of bronchial intraepithelial neoplastic lesions has been shown to be reproducible. However little is known about its biological value. The aim of this study was to assess the proliferative activity of mild (MiD), moderate (MoD), severe (SD) dysplasia and carcinoma in situ (CIS) by the expression of Ki67 on biopsy specimens obtained during fluorescence bronchoscopy.
  
  
  RESULTS
  The percentage of Ki67+ lesional nuclei was calculated in each lesion. In addition, the presence of Ki67 clusters (defined as a group of at least two strongly Ki67+ nuclei located in the upper third of the epithelium) and a Ki67 score were evaluated. The Ki67 score depended on the proportion of the stained nuclei and on the intensity of staining. MiD, MoD, SD and CIS showed increased Ki67 staining (respectively, 10%, 20%, 30% and 40% median values of positive cells). Thirty-one percent MiD, 77% MoD, 91% SD and 100% CIS showed one or more positive clusters. When only multiple clusters were considered the difference between high- and low-grade lesions was accentuated. Ki67+ clusters were more frequent in SD (91%) and CIS (94%) compared with MiD (15%) and MoD (22%). This difference was statistically significant (P < 0.01). Evaluation of the Ki67 score was in line with the above results: high grade lesions (SD and CIS) more often showed scores >4 (P = 0.05 between MiD plus MoD versus SD plus CIS).
  
  
  CONCLUSIONS
  Ki67 expression increases from MiD to CIS with a statistically significant difference between MiD plus MoD and SD plus CIS. These results suggest that, in terms of Ki67 positivity, SD behaves like CIS rather than like MiD or MoD.
authors.affiliation: Départment de Médicine Interne et Laboratoire d'Investigation Clinique et d'Oncologie Expérimentale HJ Tagnon, Institut Jules Bordet, Brussels, Belgium.
authors.forename: A-P
authors.initials: AP
authors.lastname: Meert
authors.forename: F
authors.initials: F
authors.lastname: Feoli
authors.forename: B
authors.initials: B
authors.lastname: Martin
authors.forename: J-M
authors.initials: JM
authors.lastname: Verdebout
authors.forename: C
authors.initials: C
authors.lastname: Mascaux
authors.forename: A
authors.initials: A
authors.lastname: Verhest
authors.forename: V
authors.initials: V
authors.lastname: Ninane
authors.forename: J-P
authors.initials: JP
authors.lastname: Sculier
mesh_terms: D001706:Biopsy; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D001999:Bronchoscopy; D002278:Carcinoma in Situ / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D011230:Precancerous Conditions / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D014944:World Health Organization
chemical_list: D019394:Ki-67 Antigen