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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

Schmitt-Graff, Annette
Koeninger, A.
Olschewski, Manfred
Haxelmans, S.
Nitschke, Roland
Lifschitz-Mercer, B.
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Published in Histopathology. 2007, vol. 51, no. 1, p. 87-97
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.
Keywords Carcinoma, Squamous Cell/ metabolism/pathologyCase-Control StudiesCell ProliferationCell Transformation, Neoplastic/geneticsCervix Uteri/metabolism/pathologyCondylomata Acuminata/metabolism/pathologyDesmoplakins/genetics/ metabolismDisease ProgressionFemaleGene Expression Regulation, NeoplasticHumansKi-67 Antigen/genetics/ metabolismPlakophilins/genetics/ metabolismRNA, Messenger/genetics/metabolismRetinol-Binding Proteins/genetics/ metabolismRetinol-Binding Proteins, CellularUterine Cervical Neoplasms/ metabolism/pathology
Stable URL http://archive-ouverte.unige.ch/unige:11081
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PMID: 17593084
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