Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82234
Title:
Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia.
Authors:
Davidson, Emma J; Morris, L S; Scott, I S; Rushbrook, S M; Bird, K; Laskey, R A; Wilson, Godfrey E; Kitchener, Henry C; Coleman, N; Stern, Peter L
Abstract:
Vulval intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. To investigate the functional properties of VIN, the expression of several proteins involved in the regulation of the cell cycle as well as in situ DNA replication competence was analysed by immunohistochemistry. Snap-frozen vulval biopsies were graded as normal squamous epithelium (n=6), undifferentiated HPV positive VIN 1 (n=3), VIN 2 (n=8) and VIN 3 (n=20). Immunohistochemistry was performed using the following markers: cyclin D1 (expressed in middle/late G1), cyclin B1 (expressed in G2/early M), phosphorylated histone H3 (expressed during mitosis) and minichromosome maintenance (Mcm) proteins 2 and 5 (expressed during the cell cycle, but not in differentiated or quiescent cells). In situ DNA replication competence was used to identify S-phase cells. The percentage of positively stained nuclei in three representative microscopic fields was calculated per biopsy. In normal vulva, the expression of all markers was restricted to the proliferative compartment of the basal layer of the epithelium. In contrast in high-grade VIN, the majority of epithelial cells expressed the Mcm proteins from basal to superficial layer. The detection of cyclins B1 and D1, phospho-histone H3 and in situ DNA replication was also found through the full thickness of these lesions but by a lower proportion of the cells. This is consistent with these markers providing a series of 'snapshots' of the cell cycle status of individual cells. The low-grade VIN showed reduced expression of the cell cycle markers in relation to the level of dysplasia. The combination of these analyses establishes that the majority of VIN cells remain in a functional replicative or prereplicative state of the cell cycle. Clinical application of these analyses may provide a basis for improved diagnosis of VIN.
Affiliation:
Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Minichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia. 2003, 88 (2):257-62 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
27-Jan-2003
URI:
http://hdl.handle.net/10541/82234
DOI:
10.1038/sj.bjc.6600729
PubMed ID:
12610511
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorDavidson, Emma J-
dc.contributor.authorMorris, L S-
dc.contributor.authorScott, I S-
dc.contributor.authorRushbrook, S M-
dc.contributor.authorBird, K-
dc.contributor.authorLaskey, R A-
dc.contributor.authorWilson, Godfrey E-
dc.contributor.authorKitchener, Henry C-
dc.contributor.authorColeman, N-
dc.contributor.authorStern, Peter L-
dc.date.accessioned2009-09-23T09:28:32Z-
dc.date.available2009-09-23T09:28:32Z-
dc.date.issued2003-01-27-
dc.identifier.citationMinichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia. 2003, 88 (2):257-62 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid12610511-
dc.identifier.doi10.1038/sj.bjc.6600729-
dc.identifier.urihttp://hdl.handle.net/10541/82234-
dc.description.abstractVulval intraepithelial neoplasia (VIN) is defined histopathologically by distinctive abnormalities of cellular maturation and differentiation. To investigate the functional properties of VIN, the expression of several proteins involved in the regulation of the cell cycle as well as in situ DNA replication competence was analysed by immunohistochemistry. Snap-frozen vulval biopsies were graded as normal squamous epithelium (n=6), undifferentiated HPV positive VIN 1 (n=3), VIN 2 (n=8) and VIN 3 (n=20). Immunohistochemistry was performed using the following markers: cyclin D1 (expressed in middle/late G1), cyclin B1 (expressed in G2/early M), phosphorylated histone H3 (expressed during mitosis) and minichromosome maintenance (Mcm) proteins 2 and 5 (expressed during the cell cycle, but not in differentiated or quiescent cells). In situ DNA replication competence was used to identify S-phase cells. The percentage of positively stained nuclei in three representative microscopic fields was calculated per biopsy. In normal vulva, the expression of all markers was restricted to the proliferative compartment of the basal layer of the epithelium. In contrast in high-grade VIN, the majority of epithelial cells expressed the Mcm proteins from basal to superficial layer. The detection of cyclins B1 and D1, phospho-histone H3 and in situ DNA replication was also found through the full thickness of these lesions but by a lower proportion of the cells. This is consistent with these markers providing a series of 'snapshots' of the cell cycle status of individual cells. The low-grade VIN showed reduced expression of the cell cycle markers in relation to the level of dysplasia. The combination of these analyses establishes that the majority of VIN cells remain in a functional replicative or prereplicative state of the cell cycle. Clinical application of these analyses may provide a basis for improved diagnosis of VIN.en
dc.language.isoenen
dc.subjectBiological Tumour Markersen
dc.subjectVulvar Canceren
dc.subject.meshBiopsy-
dc.subject.meshCarcinoma in Situ-
dc.subject.meshCell Cycle-
dc.subject.meshCell Cycle Proteins-
dc.subject.meshCyclin B-
dc.subject.meshCyclin D1-
dc.subject.meshDNA Replication-
dc.subject.meshDNA, Neoplasm-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFemale-
dc.subject.meshHistones-
dc.subject.meshHumans-
dc.subject.meshImmunoenzyme Techniques-
dc.subject.meshNuclear Proteins-
dc.subject.meshSchizosaccharomyces pombe Proteins-
dc.subject.meshTumor Markers, Biological-
dc.subject.meshVulvar Neoplasms-
dc.titleMinichromosome maintenance (Mcm) proteins, cyclin B1 and D1, phosphohistone H3 and in situ DNA replication for functional analysis of vulval intraepithelial neoplasia.en
dc.typeArticleen
dc.contributor.departmentImmunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren

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