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

A. Schmitt-Graeff, A. Koeninger, M. Olschewski, S. Haxelmans, R. Nitschke, M. L. Bochaton-Piallat, B. Lifschitz-Mercer, G. Gabbiani, L. Langbein, B. Czernobilsky

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: 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.

Original languageEnglish
Pages (from-to)87-97
Number of pages11
JournalHistopathology
Volume51
Issue number1
DOIs
StatePublished - Jul 2007
Externally publishedYes

Keywords

  • Cellular retinol-binding protein-1
  • Desmoplakin
  • Plakophilin-1
  • Proliferative activity
  • Squamous cell lesions of uterine cervix

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