Immunohistochemical localization of telomerase hTERT protein and analysis of clonality in multifocal vulvar intraepithelial neoplasia
Vulvar intraepithelial neoplasias (VINs) are potentially premalignant lesions of the squamous mucosa. The immunohistochemical distribution of the catalytic protein subunit of telomerase (hTERT) and the patterns of X chromosome inactivation were investigated as markers of neoplasia in samples from a...
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| Veröffentlicht in: | American journal of clinical pathology 2000-09, Vol.114 (3), p.371-379 |
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| creator | WADA, Hiroko ENOMOTO, Takayuki LOPEZ-URIBE, Daniel SHROYER, Kenneth R YOSHINO, Kiyoshi OZAKI, Keiichiro KURACHI, Hirohisa NOMURA, Taisei MURATA, Yuji NAM KIM WEINRICH, Scott LEA-CHOU, Elaine |
| description | Vulvar intraepithelial neoplasias (VINs) are potentially premalignant lesions of the squamous mucosa. The immunohistochemical distribution of the catalytic protein subunit of telomerase (hTERT) and the patterns of X chromosome inactivation were investigated as markers of neoplasia in samples from a patient with multifocal and diffuse VIN. hTERT nuclear staining in VIN correlated with squamous maturation and the degree of nuclear atypia. Normal mucosa revealed faint nuclear staining of parabasal cells and lower intermediate layer squamous cells. Monoclonal composition was demonstrated in 0 of 3 samples of VIN1, 2 of 3 samples of VIN2, and 13 of 13 samples of VIN3. The patterns of X chromosome inactivation indicated intramucosal extension and multifocal origin of individual lesions. Five samples of histologically normal vulvar squamous epithelium revealed a random pattern of X chromosome inactivation, consistent with polyclonal composition. All 19 samples from 9 lesions contained human papillomavirus (HPV)-16 sequences. Neither mutations in the p53 tumor suppressor gene or K-ras oncogenes nor loss of heterozygosity at 7 chromosomal loci were detected in any of the 19 samples of VIN. These results demonstrate that HPV-associated VIN may result from multifocal and diffuse 2-dimensional intraepithelial expansion of an immortalized monoclonal cell population. |
| doi_str_mv | 10.1093/ajcp/114.3.371 |
| format | Article |
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The immunohistochemical distribution of the catalytic protein subunit of telomerase (hTERT) and the patterns of X chromosome inactivation were investigated as markers of neoplasia in samples from a patient with multifocal and diffuse VIN. hTERT nuclear staining in VIN correlated with squamous maturation and the degree of nuclear atypia. Normal mucosa revealed faint nuclear staining of parabasal cells and lower intermediate layer squamous cells. Monoclonal composition was demonstrated in 0 of 3 samples of VIN1, 2 of 3 samples of VIN2, and 13 of 13 samples of VIN3. The patterns of X chromosome inactivation indicated intramucosal extension and multifocal origin of individual lesions. Five samples of histologically normal vulvar squamous epithelium revealed a random pattern of X chromosome inactivation, consistent with polyclonal composition. All 19 samples from 9 lesions contained human papillomavirus (HPV)-16 sequences. Neither mutations in the p53 tumor suppressor gene or K-ras oncogenes nor loss of heterozygosity at 7 chromosomal loci were detected in any of the 19 samples of VIN. These results demonstrate that HPV-associated VIN may result from multifocal and diffuse 2-dimensional intraepithelial expansion of an immortalized monoclonal cell population.</description><identifier>ISSN: 0002-9173</identifier><identifier>EISSN: 1943-7722</identifier><identifier>DOI: 10.1093/ajcp/114.3.371</identifier><identifier>PMID: 10989637</identifier><identifier>CODEN: AJCPAI</identifier><language>eng</language><publisher>Chicago, IL: American Society of Clinical Pathologists</publisher><subject>Biological and medical sciences ; Carcinoma in Situ - enzymology ; Carcinoma in Situ - pathology ; Catalytic Domain ; Clone Cells ; DNA Primers - chemistry ; DNA-Binding Proteins ; Dosage Compensation, Genetic ; Female ; Female genital diseases ; Genes, p53 ; Genes, ras ; Gynecology. Andrology. Obstetrics ; Humans ; Immunohistochemistry ; Loss of Heterozygosity ; Medical sciences ; Middle Aged ; Mutation ; Polymerase Chain Reaction ; RNA ; Telomerase - analysis ; Tumors ; Vulvar Neoplasms - enzymology ; Vulvar Neoplasms - pathology ; X Chromosome</subject><ispartof>American journal of clinical pathology, 2000-09, Vol.114 (3), p.371-379</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c426t-5f2ba47751c579e78a0a9e0d29091ef33bc3be21cc370c622a92833d5fb12ef53</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1474371$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10989637$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WADA, Hiroko</creatorcontrib><creatorcontrib>ENOMOTO, Takayuki</creatorcontrib><creatorcontrib>LOPEZ-URIBE, Daniel</creatorcontrib><creatorcontrib>SHROYER, Kenneth R</creatorcontrib><creatorcontrib>YOSHINO, Kiyoshi</creatorcontrib><creatorcontrib>OZAKI, Keiichiro</creatorcontrib><creatorcontrib>KURACHI, Hirohisa</creatorcontrib><creatorcontrib>NOMURA, Taisei</creatorcontrib><creatorcontrib>MURATA, Yuji</creatorcontrib><creatorcontrib>NAM KIM</creatorcontrib><creatorcontrib>WEINRICH, Scott</creatorcontrib><creatorcontrib>LEA-CHOU, Elaine</creatorcontrib><title>Immunohistochemical localization of telomerase hTERT protein and analysis of clonality in multifocal vulvar intraepithelial neoplasia</title><title>American journal of clinical pathology</title><addtitle>Am J Clin Pathol</addtitle><description>Vulvar intraepithelial neoplasias (VINs) are potentially premalignant lesions of the squamous mucosa. The immunohistochemical distribution of the catalytic protein subunit of telomerase (hTERT) and the patterns of X chromosome inactivation were investigated as markers of neoplasia in samples from a patient with multifocal and diffuse VIN. hTERT nuclear staining in VIN correlated with squamous maturation and the degree of nuclear atypia. Normal mucosa revealed faint nuclear staining of parabasal cells and lower intermediate layer squamous cells. Monoclonal composition was demonstrated in 0 of 3 samples of VIN1, 2 of 3 samples of VIN2, and 13 of 13 samples of VIN3. The patterns of X chromosome inactivation indicated intramucosal extension and multifocal origin of individual lesions. Five samples of histologically normal vulvar squamous epithelium revealed a random pattern of X chromosome inactivation, consistent with polyclonal composition. All 19 samples from 9 lesions contained human papillomavirus (HPV)-16 sequences. Neither mutations in the p53 tumor suppressor gene or K-ras oncogenes nor loss of heterozygosity at 7 chromosomal loci were detected in any of the 19 samples of VIN. These results demonstrate that HPV-associated VIN may result from multifocal and diffuse 2-dimensional intraepithelial expansion of an immortalized monoclonal cell population.</description><subject>Biological and medical sciences</subject><subject>Carcinoma in Situ - enzymology</subject><subject>Carcinoma in Situ - pathology</subject><subject>Catalytic Domain</subject><subject>Clone Cells</subject><subject>DNA Primers - chemistry</subject><subject>DNA-Binding Proteins</subject><subject>Dosage Compensation, Genetic</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Genes, p53</subject><subject>Genes, ras</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Loss of Heterozygosity</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Polymerase Chain Reaction</subject><subject>RNA</subject><subject>Telomerase - analysis</subject><subject>Tumors</subject><subject>Vulvar Neoplasms - enzymology</subject><subject>Vulvar Neoplasms - pathology</subject><subject>X Chromosome</subject><issn>0002-9173</issn><issn>1943-7722</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE1r3DAQhkVpaTZprz0WH0pv3ujDXlnHEjZNIBAo27MYa0esgmy5khzY3PO_K7MLyUESM3rmRXoI-cbomlElruHJTNeMNWuxFpJ9ICumGlFLyflHsqKU8loxKS7IZUpPlDLe0eYzuSijndoIuSKv98Mwj-HgUg7mgIMz4Csfyu5eILswVsFWGX0YMELC6rDb_tlVUwwZ3VjBuC8L_DG5tIDGh1K5fKzK5TD77OwSVT3P_hliaeYIOLl8QO9Ke8QweUgOvpBPFnzCr-fzivy93e5u7uqHx9_3N78eatPwTa5by3topGyZaaVC2QEFhXTPFVUMrRC9ET1yZoyQ1Gw4B8U7Ifat7RlH24or8vOUWz7wb8aU9eCSQe-hPGVOumjbdILSAq5PoIkhpYhWT9ENEI-aUb2I14t4XcRroYv4MvD9nDz3A-7f4SfTBfhxBiAVJTbCaFx64xrZLDn_AZjdj48</recordid><startdate>20000901</startdate><enddate>20000901</enddate><creator>WADA, Hiroko</creator><creator>ENOMOTO, Takayuki</creator><creator>LOPEZ-URIBE, Daniel</creator><creator>SHROYER, Kenneth R</creator><creator>YOSHINO, Kiyoshi</creator><creator>OZAKI, Keiichiro</creator><creator>KURACHI, Hirohisa</creator><creator>NOMURA, Taisei</creator><creator>MURATA, Yuji</creator><creator>NAM KIM</creator><creator>WEINRICH, Scott</creator><creator>LEA-CHOU, Elaine</creator><general>American Society of Clinical Pathologists</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20000901</creationdate><title>Immunohistochemical localization of telomerase hTERT protein and analysis of clonality in multifocal vulvar intraepithelial neoplasia</title><author>WADA, Hiroko ; ENOMOTO, Takayuki ; LOPEZ-URIBE, Daniel ; SHROYER, Kenneth R ; YOSHINO, Kiyoshi ; OZAKI, Keiichiro ; KURACHI, Hirohisa ; NOMURA, Taisei ; MURATA, Yuji ; NAM KIM ; WEINRICH, Scott ; LEA-CHOU, Elaine</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-5f2ba47751c579e78a0a9e0d29091ef33bc3be21cc370c622a92833d5fb12ef53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Biological and medical sciences</topic><topic>Carcinoma in Situ - enzymology</topic><topic>Carcinoma in Situ - pathology</topic><topic>Catalytic Domain</topic><topic>Clone Cells</topic><topic>DNA Primers - chemistry</topic><topic>DNA-Binding Proteins</topic><topic>Dosage Compensation, Genetic</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Genes, p53</topic><topic>Genes, ras</topic><topic>Gynecology. Andrology. 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The immunohistochemical distribution of the catalytic protein subunit of telomerase (hTERT) and the patterns of X chromosome inactivation were investigated as markers of neoplasia in samples from a patient with multifocal and diffuse VIN. hTERT nuclear staining in VIN correlated with squamous maturation and the degree of nuclear atypia. Normal mucosa revealed faint nuclear staining of parabasal cells and lower intermediate layer squamous cells. Monoclonal composition was demonstrated in 0 of 3 samples of VIN1, 2 of 3 samples of VIN2, and 13 of 13 samples of VIN3. The patterns of X chromosome inactivation indicated intramucosal extension and multifocal origin of individual lesions. Five samples of histologically normal vulvar squamous epithelium revealed a random pattern of X chromosome inactivation, consistent with polyclonal composition. All 19 samples from 9 lesions contained human papillomavirus (HPV)-16 sequences. Neither mutations in the p53 tumor suppressor gene or K-ras oncogenes nor loss of heterozygosity at 7 chromosomal loci were detected in any of the 19 samples of VIN. These results demonstrate that HPV-associated VIN may result from multifocal and diffuse 2-dimensional intraepithelial expansion of an immortalized monoclonal cell population.</abstract><cop>Chicago, IL</cop><pub>American Society of Clinical Pathologists</pub><pmid>10989637</pmid><doi>10.1093/ajcp/114.3.371</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | American journal of clinical pathology, 2000-09, Vol.114 (3), p.371-379 |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals |
| subjects | Biological and medical sciences Carcinoma in Situ - enzymology Carcinoma in Situ - pathology Catalytic Domain Clone Cells DNA Primers - chemistry DNA-Binding Proteins Dosage Compensation, Genetic Female Female genital diseases Genes, p53 Genes, ras Gynecology. Andrology. Obstetrics Humans Immunohistochemistry Loss of Heterozygosity Medical sciences Middle Aged Mutation Polymerase Chain Reaction RNA Telomerase - analysis Tumors Vulvar Neoplasms - enzymology Vulvar Neoplasms - pathology X Chromosome |
| title | Immunohistochemical localization of telomerase hTERT protein and analysis of clonality in multifocal vulvar intraepithelial neoplasia |
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