Original ContributionsLoss of cytokeratin 14 expression is related to human papillomavirus type and lesion grade in squamous intraepithelial lesions of the cervix*,**
Section snippets
Choice of specimens
Ten control normal cervical tissues from patients with no history of SIL and 49 low-grade SIL specimens were from a previously reported series that examined cyclin expression.1 Ten additional normal cervical biopsy specimens and 30 high-grade SILs were identified from the routine diagnostic files of the Department of Pathology of Royal Liverpool University Hospital, and diagnoses were confirmed by 2 gynecologic pathologists (C.S.H. and I.W.M.).
Six-micrometer parallel formalin-fixed paraffin
HPV typing
The 209-bp β-globin fragment was amplified, showing adequate DNA quality from all tissues. All normal cervical tissue controls were negative for HPV. Twenty-seven low-grade SILs1 were infected with high-risk HPV types (HPV 16, n = 5; 18, n = 4; 31, n = 1; 33, n = 1; 39, n = 2; 51, n = 2; 52, n = 3; 56, n = 1; 58, n = 5; 66, n = 3), and 24 were infected with low-risk HPV types (HPV 6, n = 12; 11, n = 6; 42, n = 3; 43, n = 2; 44, n = 1). Double infections (included in the above figures) were
Discussion
There were 2 main findings in this study: (1) absence of cytokeratin 14 expression is associated with high-risk HPV infection and occurs more frequently in high-grade SILs; and (2) dedifferentiation, with loss of cytokeratin 13 or involucrin expression, occurs only in high-grade lesions. Overall, disruption of squamous differentiation occurred more often in high-grade than in low-grade lesions and was associated with high-risk HPV infection.
In most of the low-grade SILs, cytokeratin 14
Acknowledgements
The authors thank Dr E.-M. de Villiers (Deutches Krebsforschungszentrum, Heidelberg, Germany), Dr G. Orth (Institut Pasteur, Paris, France), Dr Y. Matsukura (National Institute of Health, Tokyo, Japan), and A. T. Lorincz (DiGene Diagnostics, Gaithersburg, MD) for providing HPV plasmid clones.
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Expression of papillomavirus L1 proteins regulated by authentic gene codon usage is favoured in G2/M-like cells in differentiating keratinocytes
2010, VirologyCitation Excerpt :One may argue that co-expression of the L1 protein encoded by HPV6b Nat L1 gene with cyclin B1 is not an association with a cell cycle phase in KCs, probably due to that the differentiating KCs only express B-type cyclins. Based on published studies, the link between cell cycle exit, proliferation and differentiation in KCs is still intricate (Mannik et al., 2009; Southern et al., 2001). Differentiation of KCs in culture does not prohibit cells from re-entering the cell cycle and de-differentiating (Mannik et al., 2009).
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Supported by grants from Wellbeing and the Royal College of Obstetricians and Gynaecologists (H1/96) and the University of Liverpool.
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Address correspondence and reprint requests to C. Simon Herrington, Department of Pathology, University of Liverpool, Royal Liverpool University Hospital, Daulby St, Liverpool L69 3GA, England.