HPV related VIN: highly proliferative and diminished responsiveness to extracellular signals
Open accessAbstract
Vulvar intraepithelial neoplasia (VIN) is a premalignant disorder caused by human papillomaviruses. Basic knowledge about the molecular pathogenesis of VIN is sparse. Therefore, we have analyzed the gene expression profile of 9 VIN samples in comparison to 10 control samples by using genome wide Affymetrix Human U133A plus2 GeneChips. Results were validated by quantitative real‐time RT‐PCR analysis and immunostaining of a few representative genes (TACSTD1, CCNE2, AR and ESR1). Significance analysis of microarrays (SAM) showed that 1,497 genes were differentially expressed in VIN compared to controls. By analyzing the biological processes affected by the observed differences, we found that VIN appears to be a highly proliferative disease; many cyclins (CCNA, CCNB and CCNE) and almost all prereplication complex proteins are upregulated. Thereby, VIN does not seem to depend for its proliferation on paracrine or endocrine signals. Many receptors (for example ESR1 and AR) and ligands are downregulated. Furthermore, although VIN is not an invasive disease, the inhibition of expression of a marked number of cell–cell adhesion molecules seems to indicate development towards invasion. Upon reviewing apoptosis and angiogenesis, it was observed that these processes have not become significantly disregulated in VIN. In conclusion: although VIN is still a premalignant disease, it already displays several hallmarks of cancer. © 2007 Wiley‐Liss, Inc.
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Human vulvar intraepithelial neoplasias (VIN) that bypassed senescence via inactivation of RB family and p53 (Santegoets et al., 2007) also show hyperinduction of the replication factors studied here (Figure S1E).
“It remains to be determined whether our observations in fibroblasts can be extended to other cells types, though it is interesting that, human vulvar intraepithelial neoplesias (VIN) that have bypassed senescence through inactivation of the RB family and p53 (Santegoets et al., 2007) also show hyperinduction of the replication factors studied here (Figure S1E).”
From Dissecting the Unique Role of the Retinoblastoma Tumor Suppressor during Cellular Senescence (2010) · cites this paper as Santegoets et al., 2007
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Cites
Hanahan, D., & Weinberg, R. A. (2000) · Cell · doi:10.1016/s0092-8674(00)81683-9 · Cited by 29,219 · see citing works
Bolstad, B. M., Irizarry, R. A., Åstrand, M., & Speed, T. P. (2003) · Bioinformatics · doi:10.1093/bioinformatics/19.2.185 · Cited by 8,185 · see citing works
Clifford, G., Gallus, S., Herrero, R., Muñóz, N., Snijders, P. J. F., Vaccarella, S., PTH, A., Catterina Ferreccio, R., Hieu, N., Matos, E., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)67069-9 · Cited by 1,091 · see citing works
van den Brule, A. J. C., Pol, R. P., Daalmeijer, N. F., Schouls, L. M., Meijer, C. J. L. M., & Snijders, P. J. F. (2002) · Journal of Clinical Microbiology · doi:10.1128/jcm.40.3.779-787.2002 · Cited by 553 · see citing works
Kjellberg, L., Hallmans, G., Åhren, A.-M., Johansson, R., Bergman, F., Wadell, G., Ångström, T., & Dillner, J. (2000) · British Journal of Cancer · doi:10.1054/bjoc.1999.1100 · Cited by 346 · see citing works
van Seters, M., van Beurden, M., & de Craen, A. J. M. (2005) · Gynecologic Oncology · doi:10.1016/j.ygyno.2005.02.012 · Cited by 339 · see citing works
Self-citationSideri, M. G., Jones, R. W., Wilkinson, E. J., Preti, M., Heller, D. S., Scurry, J., Haefner, H. K., & Neill, S. (2006) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000201921.69949.10 · Cited by 336 · see citing works
Gonzalez, S. L., Stremlau, M., He, X., Basile, J. R., & Münger, K. (2001) · Journal of Virology · doi:10.1128/jvi.75.16.7583-7591.2001 · Cited by 312 · see citing works
Salem, M. L. (2004) · Current Drug Targets - Inflammation & Allergy · doi:10.2174/1568010043483944 · Cited by 289 · see citing works
Vulvar Intraepithelial Neoplasia
Jones, R. W., Rowan, D., & Stewart, A. W. (2005) · Obstetrics and Gynecology · doi:10.1097/01.aog.0000187301.76283.7f · Cited by 274 · see citing works
p16 Expression in the Female Genital Tract and Its Value in Diagnosis
O’Neill, C., & McCluggage, W. G. (2006) · Advances in Anatomic Pathology · doi:10.1097/01.pap.0000201828.92719.f3 · Cited by 227 · see citing works
Vulvar Squamous Cell Carcinoma in Young Women: A Clinicopathologic Study of 21 Cases
Al-Ghamdi, A., Freedman, D., Miller, D. M., Poh, C. F.-Y., Rosin, M. P., Zhang, L., & Gilks, C. B. (2002) · Gynecologic Oncology · doi:10.1006/gyno.2001.6466 · Cited by 158 · see citing works
Sideri, M., Jones, R. W., Wilkinson, E. J., Preti, M., Heller, D. S., Scurry, J., Haefner, H. K., & Neill, S. (2005) · PubMed · Cited by 155 · see citing works
p16INK4A expression as biomarker for HPV 16-related vulvar neoplasias
Riethdorf, S., Neffen, E., Čviko, A., Löning, T., Crum, C. P., & Riethdorf, L. (2004) · Human Pathology · doi:10.1016/j.humpath.2004.09.004 · Cited by 121 · see citing works
Clonal History of Papillomavirus-Induced Dysplasia in the Female Lower Genital Tract
Vinokurova, S., Wentzensen, N., Einenkel, J., Klaes, R., Ziegert, C., Melsheimer, P., Sartor, H., Horn, L., Höckel, M., & Doeberitz, M. V. K. (2005) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/dji428 · Cited by 109 · see citing works
Chiasson, M. A. (1997) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(97)00069-0 · Cited by 99 · see citing works
van Poelgeest, M. I. E., van Seters, M., van Beurden, M., Kwappenberg, K. M. C., Heijmans‐Antonissen, C., Drijfhout, J. W., Melief, C. J. M., Kenter, G. G., Helmerhorst, T. J. M., Offringa, R., et al. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0616 · Cited by 91 · see citing works
Self-citationSexual Function and Somatopsychic Reactions in Vulvectomy‐Operated Women and their Partners
ANDREASSON, B., Moth, I., Jensen, S. B., & Bock, J. E. (1986) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.3109/00016348609158221 · Cited by 73 · see citing works
van Seters, M., Fons, G., & van Beurden, M. (2002) · PubMed · Cited by 65 · see citing works
Self-citationRufforny, I., Wilkinson, E. J., Liu, C., Zhu, H., Buteral, M., & Massoll, N. A. (2005) · Journal of Lower Genital Tract Disease · doi:10.1097/00128360-200504000-00007 · Cited by 48 · see citing works
Goffin, F., Mayrand, M., Gauthier, P., Alobaid, A. S., Lussier, C., Provencher, D. M., Drouin, P., Franco, E. L., & Coutlée, F. (2006) · Journal of Medical Virology · doi:10.1002/jmv.20628 · Cited by 42 · see citing works
Cyclin D1 and retinoblastoma protein in vulvar cancer and adjacent lesions
Rolfe, K. J., Crow, J. C., Benjamin, E. O., Reid, W. M. N., MacLean, A., & Perrett, C. W. (2001) · International Journal of Gynecological Cancer · doi:10.1046/j.1525-1438.2001.01039.x · Cited by 39 · see citing works
Hanifi‐Moghaddam, P., Boers-Sijmons, B., Klaassens, A. H. A., van Wijk, F. H., den Bakker, M. A., Ott, M., Shipley, G. L., Verheul, H. A. M., Kloosterboer, H. J., Burger, C. W., et al. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-006-0146-1 · Cited by 20 · see citing works
Self-citationKlaassens, A. H. A., van Wijk, F. H., Hanifi‐Moghaddam, P., Sijmons, B., Ewing, P. C., Kate-Booij, M. J. T., Kooi, G. S., Kloosterboer, H. J., Blok, L. J., & Burger, C. W. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2005.12.077 · Cited by 18 · see citing works
Self-citationContemporary experience with the management of vulval intraepithelial neoplasia in Northern Ireland
Zawislak, A. A., Price, J., Dobbs, S. P., McClelland, H. R., & McCluggage, W. G. (2006) · International Journal of Gynecological Cancer · doi:10.1111/j.1525-1438.2006.00375.x · Cited by 16 · see citing works
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- Zawislak AA, Price JH, Dobbs SP, McClelland HR, McCluggage WG. The management of vulval intraepithelial neoplasia in Northern Ireland. Int J Gynecol Cancer 2006;16:780-5.
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- Authors
- Santegoets, L. A. M., Seters, M. V., Helmerhorst, T. J. M., Heijmans‐Antonissen, C., Hanifi‐Moghaddam, P., Ewing, P. C., van IJcken, W. F. J., van der Spek, P. J., van der Meijden, W. I., & Blok, L. J.
- Affiliations
- Erasmus MC (NL)
- Corresponding author
- Santegoets, Lindy A.M.
- ORCID
- Seters, Manon van
- Venue
- International Journal of Cancer
- Publisher
- Wiley
- Published
- 2007-04-30
- Volume
- 121
- Issue
- 4
- Pages
- 759-766
- ISSN
- 0020-7136 (ISSN-L)
- 1097-0215
- OpenAlex
- W1964782716
- Cited by
- 40
- References
- 25
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 6
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- International Journal of Cancer (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
- Health Sciences › Medicine › Surgery › Genital Health and Disease
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Keywords
- vulvar intraepithelial neoplasia, human papillomavirus, gene expression profiling, cell proliferation, cyclins, pre-replication complex, estrogen receptor, androgen receptor, ESR1, cell-cell adhesion molecules, invasion, apoptosis, angiogenesis, premalignant disease, cancer hallmarks
- MeSH terms
- Adult, Carcinoma in Situ, Female, Humans, Middle Aged, Precancerous Conditions, Vulvar Neoplasms, Reproducibility of Results, Signal Transduction, Cell Cycle Proteins, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, Cell Proliferation, Alphapapillomavirus
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