Cell-Cycle Control Protein Expression Is Disrupted in Anogenital Condylomata Infected With Low-Risk Human Papillomavirus Types

Rachel C. Lyman, Mary L. Wilson, C. Simon Herrington

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    Abstract

    Objective. To investigate how low-risk human papillomavirus (HPV) infection disrupts cell cycle control.

    Materials and Methods. A series of anogenital condylomata acuminata was analyzed by immunohistochemistry (IHC) for cell cycle protein expression and by polymerase chain reaction and in situ hybridization for HPV type and distribution.

    Results. Of the 27 condylomata analyzed, 17 contained HPV6 DNA, 8 contained HPV11 DNA and 2 were HPV-negative. Compared with adjacent normal squamous epithelium, there was marked up-regulation of Ki67, cyclin A, and p21 expression in HPV-infected epithelium, particularly in suprabasal keratinocytes. Cyclin E expression mapped to areas with viral DNA amplification. Cyclin D1 expression was largely confined to basal and parabasal cells but was more widespread in the condylomata than in normal epithelium. Only low-level expression of cyclin B was observed. Dual IHC confirmed that expression of p21 was considerably more widespread than p53, consistent with p53-independent expression of p21 in suprabasal keratinocytes in HPV-infected epithelium. Ki67 was expressed throughout the whole thickness of the epithelium in localized areas that were confirmed by dual IHC/in situ hybridization to map to areas of viral DNA amplification.

    Conclusions. These data show that cell-cycle disruption as a result of low-risk HPV infection is similar to that reported for productive high-risk HPV infection, suggesting that the life cycles of these 2 viral groups in suprabasal keratinocytes is similar. The reexpression of Ki67 in areas of viral DNA amplification suggests that this protein may play a role in HPV DNA replication.

    Original languageEnglish
    Pages (from-to)224-231
    Number of pages8
    JournalJournal of Lower Genital Tract Disease
    Volume12
    Issue number3
    DOIs
    Publication statusPublished - Jul 2008

    Keywords

    • papillomavirus
    • condyloma
    • cyclin
    • p21
    • p53
    • SQUAMOUS INTRAEPITHELIAL LESIONS
    • RECURRENT RESPIRATORY PAPILLOMATOSIS
    • DIFFERENTIATED KERATINOCYTES
    • DNA-SYNTHESIS
    • E7
    • P21
    • P53
    • HYBRIDIZATION
    • TRANSITION
    • INDUCTION

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