Expression of Topoisomerase IIα, Ki-67, Proliferating Cell Nuclear Antigen, p53, and Argyrophilic Nucleolar Organizer Regions in Vulvar Squamous Lesions

Brustmann, Hermann; Naudé, S. M.

doi:10.1006/gyno.2002.6747

Cited by 28 publications

(16 citation statements)

References 32 publications

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“…2 We observed a progressive increase of hTERT expression from nonneoplastic to neoplastic and finally invasive vulvar squamous epithelia similar to those noted for proliferation markers like Ki-67 and topoisomerase IIa in a previous study. 8 A comparable increase of hTERT expression was reported by Saha et al 13 for cervical intraepithelial neoplasia. They concluded that this phenomenon represents an early genetic abnormality in cervical pathogenesis, which may be assumed for vulvar neoplasia, too.…”

supporting

confidence: 72%

“…Mutation of p53 leads to an impaired function and results in stabilization of the protein, allowing its immunohistochemical detection. 8 Despite its relevance in neoplastic growth, hTERT expression has not been evaluated earlier over a range of vulvar squamous epithelial lesions. The present study is the first to assess whether hTERT upregulation and overexpression is of relevance in different kinds of VIN and in the progression to ISCC.…”

mentioning

confidence: 99%

“…5 Indeed, expression patterns were similar to those of different proliferation markers (Ki-67, topoisomerase IIa) in vulvar tissues as noted previously. 8 Several studies deal with survivin immunohistochemistry in squamous cell carcinomas of different origins. Nuclear survivin expression has been detected in the majority of esophageal squamous cell carcinomas, where it has been considered an unfavorable prognostic marker.…”

mentioning

confidence: 99%

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Expression of Human Telomerase Reverse Transcriptase in Vulvar Intraepithelial Neoplasia and Squamous Cell Carcinoma: An Immunohistochemical Study With Survivin and p53

Wellenhofer¹,

Brustmann²

2012

Archives of Pathology &Amp; Laboratory Medicine

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N Context.-Human telomerase reverse transcriptase (hTERT), an enzyme that enables cells to overcome replicative senescence and to divide indefinitely, is overexpressed in many cancers and their precursor lesions.Objective.-To test whether hTERT expression is related to neoplastic progression and resistance to apoptosis in vulvar epithelia.Design.-Immunoexpression of hTERT was evaluated in 101 formalin-fixed, paraffin-embedded archival vulvar epithelia consisting of normal squamous vulvar epithelia (n = 25), lichen sclerosus (n = 10), high-grade classic vulvar intraepithelial neoplasia (n = 16), differentiated vulvar intraepithelial neoplasia (n = 18), and vulvar invasive keratinizing squamous cell carcinoma (n = 32) and related to survivin and p53 expression. Immunostaining for all factors was scored for moderate and strong intensities with regard to quantity to determine upregulation and overexpression (score 0, 0% immunoreactive cells; score 1+, ,5% immunoreactive cells; score 2+, 5% to 50% immunoreactive cells; score 3+, .50% immunoreactive cells). Score 3+ was considered as overexpression.Results.-Nuclear hTERT immunoexpression was closely related to survivin reactivity, increased from normal vulvar squamous epithelia to lichen sclerosus and to high-grade classic vulvar intraepithelial neoplasia, differentiated vulvar intraepithelial neoplasia, and invasive keratinizing squamous cell carcinoma (P , .001), and followed the morphologic distribution of atypical squamous epithelial cells. Overexpression of hTERT was comparable to that seen for p53 in invasive keratinizing squamous cell carcinoma (P = .62); significant differences were calculated for differentiated vulvar intraepithelial neoplasia (P = .003) and highgrade classic vulvar intraepithelial neoplasia (P = .001).Conclusion.-Human telomerase reverse transcriptase is upregulated in vulvar intraepithelial neoplasia and invasive keratinizing squamous cell carcinoma compared with nonneoplastic squamous epithelia of the vulva as an apparently early and preinvasive event in the neoplastic transformation, with development of cellular longevity and resistance to apoptosis by survivin activation as associated features, independent of the etiology of vulvar intraepithelial neoplasia.(Arch Pathol Lab Med. 2012;136:1359-1365; doi: 10.5858/arpa.2011-0440-OA) I nvasive squamous cell carcinoma (ISCC) is the most common type of all invasive vulvar cancers. Vulvar intraepithelial neoplasias (VINs) are precancerous changes, defined as proliferative intraepithelial squamous lesions that display abnormal growth, exhibiting lack of cellular maturation and crowding of cells. According to the grade of dysplasia, they are designated as VIN grade 1, 2, or 3. The vast majority of VIN lesions are considered grade 2 or 3, with a distinction between these 2 grades being highly subjective. Basaloid and warty (condylomatous) or classic subtypes of VIN are associated with relatively younger women, and evidence of human papillomavirus (HPV) nucleic acids. A third, ''differentiated'' su...

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confidence: 99%

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confidence: 99%

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Expression of Human Telomerase Reverse Transcriptase in Vulvar Intraepithelial Neoplasia and Squamous Cell Carcinoma: An Immunohistochemical Study With Survivin and p53

Wellenhofer¹,

Brustmann²

2012

Archives of Pathology &Amp; Laboratory Medicine

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“…Several other investigators calculated a MIB1 positivity or labelling index, measuring the entire thickness of the epithelium or only the basal cell layer, but none of the groups used digital quantitative image analysis and mostly no distinction was made between differentiated and usual VIN, or only usual VIN was analysed. 27 Only scoring the MIB1 pattern or using a semiquantitative scoring method is less accurate. 28 Owing to deep rete pegs the measurement of the entire epithelium, as previously published by Bulten et al 15 for cervical lesions, is technically not possible in differentiated VIN lesions.…”

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confidence: 99%

MIB1 expression in basal cell layer: a diagnostic tool to identify premalignancies of the vulva

et al. 2007

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Lichen sclerosus, high-grade usual vulvar intraepithelial neoplasia (VIN) and differentiated VIN have a different malignant potential. The objective of this study was to quantify the proliferative activity in the basal region of the epithelium of vulvar premalignancies. Furthermore, we investigated whether MIB1 expression in the basal region of vulvar epithelium can be helpful in diagnosing differentiated VIN, which may be hard to discern from normal epithelium. MIB1 was used to immunohistochemically visualise proliferating cells within formalin-fixed, paraffin-embedded, archival tissue sections of different vulvar premalignancies (N ¼ 48) and normal vulvar epithelium (N ¼ 16). Automatic digital image analysis software was developed to quantify the proliferating fraction in different parts of the epithelium (MIB1 positivity index). MIB1 expression differed among the various vulvar premalignancies; a MIB1-negative basal cell layer was a distinct feature of normal vulvar epithelium. No MIB1-negative basal cell layer was noted in differentiated VIN or other vulvar premalignancies. Owing to this negative cell layer, the MIB1 proliferation index in normal vulvar epithelium was significantly lower than in vulvar premalignancies. In conclusion, MIB1 expression can be a helpful tool in diagnosing a premalignancy and has additional value especially to distinguish differentiated VIN neoplasia from normal vulvar epithelium, but cannot explain the differences in malignant potential.

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“…Endometrial angiogenesis is specific for endothelial cells that are renewed from degenerated coiled arteries and then migrate and form microvessel tubes in the final stage of menstruation [3,15]. The steps of angiogenesis are regulated by angiogenic factors and their transcription factors.…”

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confidence: 99%

Expression of ETS-1 Related to Angiogenesis in Uterine Endometrium during the Menstrual Cycle

et al. 2003

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ETS-1 has been identified as a transcription factor for angiogenesis, which is essential for the development and growth of the uterine endometrium. This characteristic prompted us to study whether ETS-1 functions as an angiogenic mediator in uterine endometrium. Immunohistochemical staining revealed that the localization of ETS-1 was similar to that of vascular endothelial cells. There was a significant correlation between microvessel counts and both ETS-1 histoscores and ets-1 mRNA levels in uterine endometrium. The ETS-1 histoscores and ets-1 mRNA levels increased in the proliferative phase, reached a peak during peri-ovulation and decreased in the secretory phase. Furthermore, the ETS-1 histoscores and ets-1 mRNA levels correlated with vascular endothelial growth factor (VEGF) levels in the proliferative phase. This indicates that ETS-1 might be an angiogenic mediator in uterine endometrium linked to VEGF in the proliferative phase.

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Expression of Topoisomerase IIα, Ki-67, Proliferating Cell Nuclear Antigen, p53, and Argyrophilic Nucleolar Organizer Regions in Vulvar Squamous Lesions

Cited by 28 publications

References 32 publications

Expression of Human Telomerase Reverse Transcriptase in Vulvar Intraepithelial Neoplasia and Squamous Cell Carcinoma: An Immunohistochemical Study With Survivin and p53

Expression of Human Telomerase Reverse Transcriptase in Vulvar Intraepithelial Neoplasia and Squamous Cell Carcinoma: An Immunohistochemical Study With Survivin and p53

MIB1 expression in basal cell layer: a diagnostic tool to identify premalignancies of the vulva

Expression of ETS-1 Related to Angiogenesis in Uterine Endometrium during the Menstrual Cycle

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