title: The Ki67+ proliferation index correlates with increased cellular retinol-binding protein-1 and the coordinated loss of plakophilin-1 and desmoplakin during progression of cervical squamous lesions.
abstract: OBJECTIVE
  To investigate the modulation of cellular retinol-binding protein (CRBP)-1 and the desmosomal plaque proteins plakophilin (PKP)-1 and desmoplakin (DP) in correlation with the Ki67+ proliferation index (PI) during the progression of cervical squamous intraepithelial lesions (SIL) to squamous cell carcinoma (SCC).
  
  
  METHODS
  Using in situ imaging by brightfield and confocal laser scanning microscopy, the expression of CRBP-1 protein and transcripts, PKP-1, DP and the Ki67 PI were analysed in 38 low-grade (L) SIL, 56 high-grade (H) SIL, 49 SCC, 30 control cervices and 10 human papillomavirus-positive condylomatous lesions.
  
  
  RESULTS
  CRBP-1+ cells increased from 11.4% in the normal cervix to 80.3% in LSILs, 92.3% in HSILs and slightly decreased to 78.3% in invasive SCCs (P = 0.0001) in close association with the Ki67 PI (r =0.41; P < 0.0001). PKP-1+ and DP+ cells were correlated (0.32; P < 0.0001) and decreased from normal (81% versus 92.3%) to LSIL (53.1% versus 85.3%), to HSIL (46.4% versus 67.5%) and SCC (35.1% versus 35.9%). The Ki67+ PI was inversely correlated with DP (-0.20, P = 0.0014) and PKP-1 (-0.19, P = 0.015). Condylomata retained low CRBP-1 and high expression of PKP-1 and DP.
  
  
  CONCLUSIONS
  The gain of CRBP-1 and the loss of desmosomal proteins occur early in cervical carcinogenesis.
authors.affiliation: Institute of Pathology, University Hospital, Freiburg, Germany. annette.schmitt-graeff@uniklinik-freiburg.de
authors.forename: A
authors.initials: A
authors.lastname: Schmitt-Graeff
authors.forename: A
authors.initials: A
authors.lastname: Koeninger
authors.forename: M
authors.initials: M
authors.lastname: Olschewski
authors.forename: S
authors.initials: S
authors.lastname: Haxelmans
authors.forename: R
authors.initials: R
authors.lastname: Nitschke
authors.forename: M-L
authors.initials: ML
authors.lastname: Bochaton-Piallat
authors.forename: B
authors.initials: B
authors.lastname: Lifschitz-Mercer
authors.forename: G
authors.initials: G
authors.lastname: Gabbiani
authors.forename: L
authors.initials: L
authors.lastname: Langbein
authors.forename: B
authors.initials: B
authors.lastname: Czernobilsky
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D003218:Condylomata Acuminata / Q000378:metabolism / Q000473:pathology; D051180:Desmoplakins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D051191:Plakophilins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D051180:Desmoplakins; D019394:Ki-67 Antigen; D051191:Plakophilins; D012333:RNA, Messenger; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular