Evidence for keratinocyte immortalization in high-grade squamous intraepithelial lesions of the cervix infected with high-risk human papillomaviruses.
In this study, we demonstrate that expression of cyclin B protein is up-regulated and persists into the upper epithelial layers in parallel with cyclin A expression in high-grade squamous intraepithelial lesions (SIL) infected with human papillomaviruses 16, 31, 33, 51, 58, 66, and 67 (n = 33). In contrast, low-grade SIL infected with human papillomaviruses 16, 18, 31, 33, 39, 51, 52, 56, 58, and 66 (n = 27) show weaker cyclin B expression confined to basal and parabasal cells despite extension of cyclin A and Ki67 expression into superficial cells. Moreover, aneusomy is present in 20% of the high-grade lesions but in none of the low-grade lesions. The persistent expression of cyclin B in high-grade SIL, and the restriction of aneusomy to high-grade SIL suggest that there is cell cycle progression. In combination with in vitro studies, this provides evidence that high-grade SIL lesions have undergone immortalization.
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Department of Pathology, University of Liverpool, Royal Liverpool University Hospital, United Kingdom.
McDicken
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Herrington
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D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000473:pathology* / Q000821:virology*; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000473:pathology*; D014412:Tumor Virus Infections / Q000473:pathology*; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000821:virology*
D018797:Cell Cycle Proteins