Down-regulated nucleoside diphosphate kinase nm23-H1 expression is unrelated to high-risk human papillomavirus but associated with progression of cervical intraepithelial neoplasia and unfavourable prognosis in cervical cancer
Objective: One of the factors leading to an invasive phenotype is the nm23 family of metastases-associated genes. Of the six known members, nm23-H1 is the most frequently studied potential anti-metastatic gene in cervical cancer. However, the possible molecular links to oncogenic human papillomaviru...
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| Veröffentlicht in: | Journal of clinical pathology 2006-10, Vol.59 (10), p.1044-1051 |
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| creator | Branca, M Giorgi, C Ciotti, M Santini, D Di Bonito, L Costa, S Benedetto, A Bonifacio, D Di Bonito, P Paba, P Accardi, L Mariani, L Ruutu, M Favalli, C Syrjänen, K |
| description | Objective: One of the factors leading to an invasive phenotype is the nm23 family of metastases-associated genes. Of the six known members, nm23-H1 is the most frequently studied potential anti-metastatic gene in cervical cancer. However, the possible molecular links to oncogenic human papillomavirus (HPV) are completely unexplored as yet. Materials and methods: As a part of the HPV-Pathogen Istituto Superiore di Sanità study, a series of 150 squamous cell carcinomas (SCCs) and 152 cervical intraepithelial neoplasia (CIN) lesions were examined by immunohistochemical staining for nm23-H1, and tested for HPV by polymerase chain reaction (PCR) with three sets of primers (MY09/11, GP5+/GP6+ and short PCR fragment). Follow-up data were available on all patients with SCC, and 67 CIN lesions were monitored by serial PCR for clearance or persistence of HPV after cone treatment. Results: A linear decrease (p = 0.001) was observed in nm23-H1 expression, starting from CIN1 (85% with normal expression), with the most dramatic down regulation on transition from CIN2 (70% normal) to CIN3 (39%) and further to SCC (25%). Reduced expression was associated with CIN3 or cancer at an odds ratio 8.72 (95% confidence interval 4.13 to 18.41). Nm23-H1 was of no use as a marker of the high-risk human papillomavirus (HR-HPV) type, and it did not predict clearance or persistence of HR-HPV after treatment of CIN. Importantly, nm23-H1 expression was a significant prognostic factor in cervical cancer, reduced expression being associated with lower survival (p = 0.022) in univariate analysis. In the multivariate (Cox) regression model, however, only the International Federation of Gynecology and Obstetrics stage (p = 0.001) and age (p = 0.011) remained independent prognostic predictors. Conclusions: Down-regulated nm23-H1 expression is markedly associated with progression from CIN2 to CIN3, and predicts poor prognosis in cervical cancer. Nm23-H1 down regulation is probably orchestrated by mechanisms independent of HR-HPV oncoproteins and is possibly related to the emergence of a proteolytic phenotype. |
| doi_str_mv | 10.1136/jcp.2005.033142 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1861749</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4022525961</sourcerecordid><originalsourceid>FETCH-LOGICAL-b512t-41ab04ee2643f90af79c45d62bcf9c52b8085f866847210cc67a7cadffa6a0e63</originalsourceid><addsrcrecordid>eNqFkktv1DAUhSMEokNhzQ5ZQrBAytSPxEk2SGigFKk8FqWws24cZ-IZxw52Mi1_l1-CpzN0gE1Xfn33-Pj6JMlTgueEMH6yksOcYpzPMWMko_eSGckKmmYk4_eTGcaUpFWR8aPkUQgrjAkrCHuYHBGes4IXbJb8euuubOrVcjIwqgbZSRrlgm4UavTQuTB0cR-ttYWgkO0pS88IUteDVyFoZ5EOaLJe7apHhzq97FKvwxp1Uw8WDTBoY1wPG-2ngOppRBCCk_qm4EqPHRq8W_6Rcy2Sym-0BIO0HT2oISLK6Li2yg0GggYEtom3trBxk4faqBsJG22HWHQQkGDj_HHyoAUT1JP9eJx8PX13sThLzz-__7B4c57WOaFj7BnUOFOK8oy1FYa2qGSWN5zWsq1kTusSl3lbcl7GDhMsJS-gkNC0LXDAirPj5PVOd5jqXjVSbe0bMXjdg_8pHGjx74nVnVi6jSAlJ0VWRYGXewHvfkwqjKLXQSpjIL58CoKXFc3KktwJkopxRvOtpef_gavYMRu7IEhREkw5JTRSJztKeheCV-2tZ4LFNmYixkxsYyZ2MYsVz_5-6oHf5yoCL_YAhPgTrY8_ocOBK2NAWZFHLt1xOozq-vYc_FpEmSIXny4X4vvFt9Pyy2UlPkb-1Y6v-9WdLn8Drxb_hA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1781026212</pqid></control><display><type>article</type><title>Down-regulated nucleoside diphosphate kinase nm23-H1 expression is unrelated to high-risk human papillomavirus but associated with progression of cervical intraepithelial neoplasia and unfavourable prognosis in cervical cancer</title><source>MEDLINE</source><source>BMJ Journals - NESLi2</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Branca, M ; Giorgi, C ; Ciotti, M ; Santini, D ; Di Bonito, L ; Costa, S ; Benedetto, A ; Bonifacio, D ; Di Bonito, P ; Paba, P ; Accardi, L ; Mariani, L ; Ruutu, M ; Favalli, C ; Syrjänen, K</creator><creatorcontrib>Branca, M ; Giorgi, C ; Ciotti, M ; Santini, D ; Di Bonito, L ; Costa, S ; Benedetto, A ; Bonifacio, D ; Di Bonito, P ; Paba, P ; Accardi, L ; Mariani, L ; Ruutu, M ; Favalli, C ; Syrjänen, K ; HPV-Pathogen Istituto Superiore di Sanità Study Group</creatorcontrib><description>Objective: One of the factors leading to an invasive phenotype is the nm23 family of metastases-associated genes. Of the six known members, nm23-H1 is the most frequently studied potential anti-metastatic gene in cervical cancer. However, the possible molecular links to oncogenic human papillomavirus (HPV) are completely unexplored as yet. Materials and methods: As a part of the HPV-Pathogen Istituto Superiore di Sanità study, a series of 150 squamous cell carcinomas (SCCs) and 152 cervical intraepithelial neoplasia (CIN) lesions were examined by immunohistochemical staining for nm23-H1, and tested for HPV by polymerase chain reaction (PCR) with three sets of primers (MY09/11, GP5+/GP6+ and short PCR fragment). Follow-up data were available on all patients with SCC, and 67 CIN lesions were monitored by serial PCR for clearance or persistence of HPV after cone treatment. Results: A linear decrease (p = 0.001) was observed in nm23-H1 expression, starting from CIN1 (85% with normal expression), with the most dramatic down regulation on transition from CIN2 (70% normal) to CIN3 (39%) and further to SCC (25%). Reduced expression was associated with CIN3 or cancer at an odds ratio 8.72 (95% confidence interval 4.13 to 18.41). Nm23-H1 was of no use as a marker of the high-risk human papillomavirus (HR-HPV) type, and it did not predict clearance or persistence of HR-HPV after treatment of CIN. Importantly, nm23-H1 expression was a significant prognostic factor in cervical cancer, reduced expression being associated with lower survival (p = 0.022) in univariate analysis. In the multivariate (Cox) regression model, however, only the International Federation of Gynecology and Obstetrics stage (p = 0.001) and age (p = 0.011) remained independent prognostic predictors. Conclusions: Down-regulated nm23-H1 expression is markedly associated with progression from CIN2 to CIN3, and predicts poor prognosis in cervical cancer. Nm23-H1 down regulation is probably orchestrated by mechanisms independent of HR-HPV oncoproteins and is possibly related to the emergence of a proteolytic phenotype.</description><identifier>ISSN: 0021-9746</identifier><identifier>EISSN: 1472-4146</identifier><identifier>DOI: 10.1136/jcp.2005.033142</identifier><identifier>PMID: 16537673</identifier><identifier>CODEN: JCPAAK</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and Association of Clinical Pathologists</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Carcinoma, Squamous Cell - enzymology ; Carcinoma, Squamous Cell - pathology ; Carcinoma, Squamous Cell - virology ; Cell cycle ; Cervical cancer ; cervical intraepithelial neoplasia ; Cervical Intraepithelial Neoplasia - enzymology ; Cervical Intraepithelial Neoplasia - pathology ; Cervical Intraepithelial Neoplasia - virology ; CIN ; Disease Progression ; Down-Regulation ; Epidemiologic Methods ; ERK ; extracellular signal-regulated kinase ; Female ; Female genital diseases ; FIGO ; Genes ; Gynecology. Andrology. Obstetrics ; high-risk human papillomavirus ; HPV ; HR-HPV ; Human papillomavirus ; Humans ; IHC ; immunohistochemistry ; International Federation of Gynecology and Obstetrics ; Investigative techniques, diagnostic techniques (general aspects) ; ISS ; Istituto Superiore di Sanità ; Kinases ; low-risk human papillomavirus ; LR-HPV ; matrix metalloproteinase ; Medical prognosis ; Medical sciences ; Metastasis ; Middle Aged ; MMP ; Multivariate analysis ; NDP ; negative predictive value ; NPV ; nucleoside diphosphate ; Nucleoside-Diphosphate Kinase - genetics ; Nucleoside-Diphosphate Kinase - metabolism ; oncogenic human papillomavirus ; Original ; Papillomaviridae - classification ; Papillomaviridae - isolation & purification ; Papillomavirus Infections - complications ; Papillomavirus Infections - enzymology ; Pathogens ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; PCR ; polymerase chain reaction ; Polymerase Chain Reaction - methods ; positive predictive value ; PPV ; Prognosis ; Proteins ; SCC ; Signal transduction ; squamous cell carcinoma ; Studies ; Tumors ; Uterine Cervical Neoplasms - enzymology ; Uterine Cervical Neoplasms - pathology ; Uterine Cervical Neoplasms - virology ; vascular endothelial growth factor ; VEGF</subject><ispartof>Journal of clinical pathology, 2006-10, Vol.59 (10), p.1044-1051</ispartof><rights>Copyright 2006 Journal of Clinical Pathology</rights><rights>2006 INIST-CNRS</rights><rights>Copyright: 2006 Copyright 2006 Journal of Clinical Pathology</rights><rights>Copyright © 2006 The BMJ Publishing Group and the Association of Clinical Pathologists</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b512t-41ab04ee2643f90af79c45d62bcf9c52b8085f866847210cc67a7cadffa6a0e63</citedby><cites>FETCH-LOGICAL-b512t-41ab04ee2643f90af79c45d62bcf9c52b8085f866847210cc67a7cadffa6a0e63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttp://jcp.bmj.com/content/59/10/1044.full.pdf$$EPDF$$P50$$Gbmj$$H</linktopdf><linktohtml>$$Uhttp://jcp.bmj.com/content/59/10/1044.full$$EHTML$$P50$$Gbmj$$H</linktohtml><link.rule.ids>114,115,230,314,723,776,780,881,3183,23550,27901,27902,53766,53768,77569,77600</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18146375$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16537673$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Branca, M</creatorcontrib><creatorcontrib>Giorgi, C</creatorcontrib><creatorcontrib>Ciotti, M</creatorcontrib><creatorcontrib>Santini, D</creatorcontrib><creatorcontrib>Di Bonito, L</creatorcontrib><creatorcontrib>Costa, S</creatorcontrib><creatorcontrib>Benedetto, A</creatorcontrib><creatorcontrib>Bonifacio, D</creatorcontrib><creatorcontrib>Di Bonito, P</creatorcontrib><creatorcontrib>Paba, P</creatorcontrib><creatorcontrib>Accardi, L</creatorcontrib><creatorcontrib>Mariani, L</creatorcontrib><creatorcontrib>Ruutu, M</creatorcontrib><creatorcontrib>Favalli, C</creatorcontrib><creatorcontrib>Syrjänen, K</creatorcontrib><creatorcontrib>HPV-Pathogen Istituto Superiore di Sanità Study Group</creatorcontrib><title>Down-regulated nucleoside diphosphate kinase nm23-H1 expression is unrelated to high-risk human papillomavirus but associated with progression of cervical intraepithelial neoplasia and unfavourable prognosis in cervical cancer</title><title>Journal of clinical pathology</title><addtitle>J Clin Pathol</addtitle><description>Objective: One of the factors leading to an invasive phenotype is the nm23 family of metastases-associated genes. Of the six known members, nm23-H1 is the most frequently studied potential anti-metastatic gene in cervical cancer. However, the possible molecular links to oncogenic human papillomavirus (HPV) are completely unexplored as yet. Materials and methods: As a part of the HPV-Pathogen Istituto Superiore di Sanità study, a series of 150 squamous cell carcinomas (SCCs) and 152 cervical intraepithelial neoplasia (CIN) lesions were examined by immunohistochemical staining for nm23-H1, and tested for HPV by polymerase chain reaction (PCR) with three sets of primers (MY09/11, GP5+/GP6+ and short PCR fragment). Follow-up data were available on all patients with SCC, and 67 CIN lesions were monitored by serial PCR for clearance or persistence of HPV after cone treatment. Results: A linear decrease (p = 0.001) was observed in nm23-H1 expression, starting from CIN1 (85% with normal expression), with the most dramatic down regulation on transition from CIN2 (70% normal) to CIN3 (39%) and further to SCC (25%). Reduced expression was associated with CIN3 or cancer at an odds ratio 8.72 (95% confidence interval 4.13 to 18.41). Nm23-H1 was of no use as a marker of the high-risk human papillomavirus (HR-HPV) type, and it did not predict clearance or persistence of HR-HPV after treatment of CIN. Importantly, nm23-H1 expression was a significant prognostic factor in cervical cancer, reduced expression being associated with lower survival (p = 0.022) in univariate analysis. In the multivariate (Cox) regression model, however, only the International Federation of Gynecology and Obstetrics stage (p = 0.001) and age (p = 0.011) remained independent prognostic predictors. Conclusions: Down-regulated nm23-H1 expression is markedly associated with progression from CIN2 to CIN3, and predicts poor prognosis in cervical cancer. Nm23-H1 down regulation is probably orchestrated by mechanisms independent of HR-HPV oncoproteins and is possibly related to the emergence of a proteolytic phenotype.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Carcinoma, Squamous Cell - enzymology</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Carcinoma, Squamous Cell - virology</subject><subject>Cell cycle</subject><subject>Cervical cancer</subject><subject>cervical intraepithelial neoplasia</subject><subject>Cervical Intraepithelial Neoplasia - enzymology</subject><subject>Cervical Intraepithelial Neoplasia - pathology</subject><subject>Cervical Intraepithelial Neoplasia - virology</subject><subject>CIN</subject><subject>Disease Progression</subject><subject>Down-Regulation</subject><subject>Epidemiologic Methods</subject><subject>ERK</subject><subject>extracellular signal-regulated kinase</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>FIGO</subject><subject>Genes</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>high-risk human papillomavirus</subject><subject>HPV</subject><subject>HR-HPV</subject><subject>Human papillomavirus</subject><subject>Humans</subject><subject>IHC</subject><subject>immunohistochemistry</subject><subject>International Federation of Gynecology and Obstetrics</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>ISS</subject><subject>Istituto Superiore di Sanità</subject><subject>Kinases</subject><subject>low-risk human papillomavirus</subject><subject>LR-HPV</subject><subject>matrix metalloproteinase</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>MMP</subject><subject>Multivariate analysis</subject><subject>NDP</subject><subject>negative predictive value</subject><subject>NPV</subject><subject>nucleoside diphosphate</subject><subject>Nucleoside-Diphosphate Kinase - genetics</subject><subject>Nucleoside-Diphosphate Kinase - metabolism</subject><subject>oncogenic human papillomavirus</subject><subject>Original</subject><subject>Papillomaviridae - classification</subject><subject>Papillomaviridae - isolation & purification</subject><subject>Papillomavirus Infections - complications</subject><subject>Papillomavirus Infections - enzymology</subject><subject>Pathogens</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>PCR</subject><subject>polymerase chain reaction</subject><subject>Polymerase Chain Reaction - methods</subject><subject>positive predictive value</subject><subject>PPV</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>SCC</subject><subject>Signal transduction</subject><subject>squamous cell carcinoma</subject><subject>Studies</subject><subject>Tumors</subject><subject>Uterine Cervical Neoplasms - enzymology</subject><subject>Uterine Cervical Neoplasms - pathology</subject><subject>Uterine Cervical Neoplasms - virology</subject><subject>vascular endothelial growth factor</subject><subject>VEGF</subject><issn>0021-9746</issn><issn>1472-4146</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkktv1DAUhSMEokNhzQ5ZQrBAytSPxEk2SGigFKk8FqWws24cZ-IZxw52Mi1_l1-CpzN0gE1Xfn33-Pj6JMlTgueEMH6yksOcYpzPMWMko_eSGckKmmYk4_eTGcaUpFWR8aPkUQgrjAkrCHuYHBGes4IXbJb8euuubOrVcjIwqgbZSRrlgm4UavTQuTB0cR-ttYWgkO0pS88IUteDVyFoZ5EOaLJe7apHhzq97FKvwxp1Uw8WDTBoY1wPG-2ngOppRBCCk_qm4EqPHRq8W_6Rcy2Sym-0BIO0HT2oISLK6Li2yg0GggYEtom3trBxk4faqBsJG22HWHQQkGDj_HHyoAUT1JP9eJx8PX13sThLzz-__7B4c57WOaFj7BnUOFOK8oy1FYa2qGSWN5zWsq1kTusSl3lbcl7GDhMsJS-gkNC0LXDAirPj5PVOd5jqXjVSbe0bMXjdg_8pHGjx74nVnVi6jSAlJ0VWRYGXewHvfkwqjKLXQSpjIL58CoKXFc3KktwJkopxRvOtpef_gavYMRu7IEhREkw5JTRSJztKeheCV-2tZ4LFNmYixkxsYyZ2MYsVz_5-6oHf5yoCL_YAhPgTrY8_ocOBK2NAWZFHLt1xOozq-vYc_FpEmSIXny4X4vvFt9Pyy2UlPkb-1Y6v-9WdLn8Drxb_hA</recordid><startdate>20061001</startdate><enddate>20061001</enddate><creator>Branca, M</creator><creator>Giorgi, C</creator><creator>Ciotti, M</creator><creator>Santini, D</creator><creator>Di Bonito, L</creator><creator>Costa, S</creator><creator>Benedetto, A</creator><creator>Bonifacio, D</creator><creator>Di Bonito, P</creator><creator>Paba, P</creator><creator>Accardi, L</creator><creator>Mariani, L</creator><creator>Ruutu, M</creator><creator>Favalli, C</creator><creator>Syrjänen, K</creator><general>BMJ Publishing Group Ltd and Association of Clinical Pathologists</general><general>BMJ</general><general>BMJ Publishing Group LTD</general><general>BMJ Group</general><scope>BSCLL</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20061001</creationdate><title>Down-regulated nucleoside diphosphate kinase nm23-H1 expression is unrelated to high-risk human papillomavirus but associated with progression of cervical intraepithelial neoplasia and unfavourable prognosis in cervical cancer</title><author>Branca, M ; Giorgi, C ; Ciotti, M ; Santini, D ; Di Bonito, L ; Costa, S ; Benedetto, A ; Bonifacio, D ; Di Bonito, P ; Paba, P ; Accardi, L ; Mariani, L ; Ruutu, M ; Favalli, C ; Syrjänen, K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b512t-41ab04ee2643f90af79c45d62bcf9c52b8085f866847210cc67a7cadffa6a0e63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Carcinoma, Squamous Cell - enzymology</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Carcinoma, Squamous Cell - virology</topic><topic>Cell cycle</topic><topic>Cervical cancer</topic><topic>cervical intraepithelial neoplasia</topic><topic>Cervical Intraepithelial Neoplasia - enzymology</topic><topic>Cervical Intraepithelial Neoplasia - pathology</topic><topic>Cervical Intraepithelial Neoplasia - virology</topic><topic>CIN</topic><topic>Disease Progression</topic><topic>Down-Regulation</topic><topic>Epidemiologic Methods</topic><topic>ERK</topic><topic>extracellular signal-regulated kinase</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>FIGO</topic><topic>Genes</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>high-risk human papillomavirus</topic><topic>HPV</topic><topic>HR-HPV</topic><topic>Human papillomavirus</topic><topic>Humans</topic><topic>IHC</topic><topic>immunohistochemistry</topic><topic>International Federation of Gynecology and Obstetrics</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>ISS</topic><topic>Istituto Superiore di Sanità</topic><topic>Kinases</topic><topic>low-risk human papillomavirus</topic><topic>LR-HPV</topic><topic>matrix metalloproteinase</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>MMP</topic><topic>Multivariate analysis</topic><topic>NDP</topic><topic>negative predictive value</topic><topic>NPV</topic><topic>nucleoside diphosphate</topic><topic>Nucleoside-Diphosphate Kinase - genetics</topic><topic>Nucleoside-Diphosphate Kinase - metabolism</topic><topic>oncogenic human papillomavirus</topic><topic>Original</topic><topic>Papillomaviridae - classification</topic><topic>Papillomaviridae - isolation & purification</topic><topic>Papillomavirus Infections - complications</topic><topic>Papillomavirus Infections - enzymology</topic><topic>Pathogens</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>PCR</topic><topic>polymerase chain reaction</topic><topic>Polymerase Chain Reaction - methods</topic><topic>positive predictive value</topic><topic>PPV</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>SCC</topic><topic>Signal transduction</topic><topic>squamous cell carcinoma</topic><topic>Studies</topic><topic>Tumors</topic><topic>Uterine Cervical Neoplasms - enzymology</topic><topic>Uterine Cervical Neoplasms - pathology</topic><topic>Uterine Cervical Neoplasms - virology</topic><topic>vascular endothelial growth factor</topic><topic>VEGF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Branca, M</creatorcontrib><creatorcontrib>Giorgi, C</creatorcontrib><creatorcontrib>Ciotti, M</creatorcontrib><creatorcontrib>Santini, D</creatorcontrib><creatorcontrib>Di Bonito, L</creatorcontrib><creatorcontrib>Costa, S</creatorcontrib><creatorcontrib>Benedetto, A</creatorcontrib><creatorcontrib>Bonifacio, D</creatorcontrib><creatorcontrib>Di Bonito, P</creatorcontrib><creatorcontrib>Paba, P</creatorcontrib><creatorcontrib>Accardi, L</creatorcontrib><creatorcontrib>Mariani, L</creatorcontrib><creatorcontrib>Ruutu, M</creatorcontrib><creatorcontrib>Favalli, C</creatorcontrib><creatorcontrib>Syrjänen, K</creatorcontrib><creatorcontrib>HPV-Pathogen Istituto Superiore di Sanità Study Group</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>BMJ Journals</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Branca, M</au><au>Giorgi, C</au><au>Ciotti, M</au><au>Santini, D</au><au>Di Bonito, L</au><au>Costa, S</au><au>Benedetto, A</au><au>Bonifacio, D</au><au>Di Bonito, P</au><au>Paba, P</au><au>Accardi, L</au><au>Mariani, L</au><au>Ruutu, M</au><au>Favalli, C</au><au>Syrjänen, K</au><aucorp>HPV-Pathogen Istituto Superiore di Sanità Study Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Down-regulated nucleoside diphosphate kinase nm23-H1 expression is unrelated to high-risk human papillomavirus but associated with progression of cervical intraepithelial neoplasia and unfavourable prognosis in cervical cancer</atitle><jtitle>Journal of clinical pathology</jtitle><addtitle>J Clin Pathol</addtitle><date>2006-10-01</date><risdate>2006</risdate><volume>59</volume><issue>10</issue><spage>1044</spage><epage>1051</epage><pages>1044-1051</pages><issn>0021-9746</issn><eissn>1472-4146</eissn><coden>JCPAAK</coden><abstract>Objective: One of the factors leading to an invasive phenotype is the nm23 family of metastases-associated genes. Of the six known members, nm23-H1 is the most frequently studied potential anti-metastatic gene in cervical cancer. However, the possible molecular links to oncogenic human papillomavirus (HPV) are completely unexplored as yet. Materials and methods: As a part of the HPV-Pathogen Istituto Superiore di Sanità study, a series of 150 squamous cell carcinomas (SCCs) and 152 cervical intraepithelial neoplasia (CIN) lesions were examined by immunohistochemical staining for nm23-H1, and tested for HPV by polymerase chain reaction (PCR) with three sets of primers (MY09/11, GP5+/GP6+ and short PCR fragment). Follow-up data were available on all patients with SCC, and 67 CIN lesions were monitored by serial PCR for clearance or persistence of HPV after cone treatment. Results: A linear decrease (p = 0.001) was observed in nm23-H1 expression, starting from CIN1 (85% with normal expression), with the most dramatic down regulation on transition from CIN2 (70% normal) to CIN3 (39%) and further to SCC (25%). Reduced expression was associated with CIN3 or cancer at an odds ratio 8.72 (95% confidence interval 4.13 to 18.41). Nm23-H1 was of no use as a marker of the high-risk human papillomavirus (HR-HPV) type, and it did not predict clearance or persistence of HR-HPV after treatment of CIN. Importantly, nm23-H1 expression was a significant prognostic factor in cervical cancer, reduced expression being associated with lower survival (p = 0.022) in univariate analysis. In the multivariate (Cox) regression model, however, only the International Federation of Gynecology and Obstetrics stage (p = 0.001) and age (p = 0.011) remained independent prognostic predictors. Conclusions: Down-regulated nm23-H1 expression is markedly associated with progression from CIN2 to CIN3, and predicts poor prognosis in cervical cancer. Nm23-H1 down regulation is probably orchestrated by mechanisms independent of HR-HPV oncoproteins and is possibly related to the emergence of a proteolytic phenotype.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and Association of Clinical Pathologists</pub><pmid>16537673</pmid><doi>10.1136/jcp.2005.033142</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9746 |
| ispartof | Journal of clinical pathology, 2006-10, Vol.59 (10), p.1044-1051 |
| issn | 0021-9746 1472-4146 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_1861749 |
| source | MEDLINE; BMJ Journals - NESLi2; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adolescent Adult Aged Aged, 80 and over Biological and medical sciences Biomarkers Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Carcinoma, Squamous Cell - enzymology Carcinoma, Squamous Cell - pathology Carcinoma, Squamous Cell - virology Cell cycle Cervical cancer cervical intraepithelial neoplasia Cervical Intraepithelial Neoplasia - enzymology Cervical Intraepithelial Neoplasia - pathology Cervical Intraepithelial Neoplasia - virology CIN Disease Progression Down-Regulation Epidemiologic Methods ERK extracellular signal-regulated kinase Female Female genital diseases FIGO Genes Gynecology. Andrology. Obstetrics high-risk human papillomavirus HPV HR-HPV Human papillomavirus Humans IHC immunohistochemistry International Federation of Gynecology and Obstetrics Investigative techniques, diagnostic techniques (general aspects) ISS Istituto Superiore di Sanità Kinases low-risk human papillomavirus LR-HPV matrix metalloproteinase Medical prognosis Medical sciences Metastasis Middle Aged MMP Multivariate analysis NDP negative predictive value NPV nucleoside diphosphate Nucleoside-Diphosphate Kinase - genetics Nucleoside-Diphosphate Kinase - metabolism oncogenic human papillomavirus Original Papillomaviridae - classification Papillomaviridae - isolation & purification Papillomavirus Infections - complications Papillomavirus Infections - enzymology Pathogens Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques PCR polymerase chain reaction Polymerase Chain Reaction - methods positive predictive value PPV Prognosis Proteins SCC Signal transduction squamous cell carcinoma Studies Tumors Uterine Cervical Neoplasms - enzymology Uterine Cervical Neoplasms - pathology Uterine Cervical Neoplasms - virology vascular endothelial growth factor VEGF |
| title | Down-regulated nucleoside diphosphate kinase nm23-H1 expression is unrelated to high-risk human papillomavirus but associated with progression of cervical intraepithelial neoplasia and unfavourable prognosis in cervical cancer |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T04%3A56%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Down-regulated%20nucleoside%20diphosphate%20kinase%20nm23-H1%20expression%20is%20unrelated%20to%20high-risk%20human%20papillomavirus%20but%20associated%20with%20progression%20of%20cervical%20intraepithelial%20neoplasia%20and%20unfavourable%20prognosis%20in%20cervical%20cancer&rft.jtitle=Journal%20of%20clinical%20pathology&rft.au=Branca,%20M&rft.aucorp=HPV-Pathogen%20Istituto%20Superiore%20di%20Sanit%C3%A0%20Study%20Group&rft.date=2006-10-01&rft.volume=59&rft.issue=10&rft.spage=1044&rft.epage=1051&rft.pages=1044-1051&rft.issn=0021-9746&rft.eissn=1472-4146&rft.coden=JCPAAK&rft_id=info:doi/10.1136/jcp.2005.033142&rft_dat=%3Cproquest_pubme%3E4022525961%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1781026212&rft_id=info:pmid/16537673&rfr_iscdi=true |