Oncogene Alterations in Carcinomas of the Uterine Cervix: Overexpression of the Epidermal Growth Factor Receptor Is Associated with Poor Prognosis
The involvement of human papillomavirus (HPV) in the development of carcinomas of the uterine cervix has been firmly established. However, other genetic alterations also play an important role in the pathogenesis of cervical cancer. Therefore, we have investigated the role of several (onco)genes in...
Gespeichert in:
| Veröffentlicht in: | Clinical cancer research 1999-03, Vol.5 (3), p.577-586 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 586 |
|---|---|
| container_issue | 3 |
| container_start_page | 577 |
| container_title | Clinical cancer research |
| container_volume | 5 |
| creator | KERSEMAEKERS, A.-M. F FLEUREN, G. J KENTER, G. G VAN DEN BROEK, L. J. C. M ULJEE, S. M HERMANS, J VAN DE VIJVER, M. J |
| description | The involvement of human papillomavirus (HPV) in the development of carcinomas of the uterine cervix has been firmly established.
However, other genetic alterations also play an important role in the pathogenesis of cervical cancer. Therefore, we have
investigated the role of several (onco)genes in cervical carcinoma.
In tumors from 136 patients with stage I and II cancer of the uterine cervix, the expression of epidermal growth factor receptor
(EGFR), c-erbB-2/neu, p53, and murine double minute 2 (MDM-2) was studied using immunohistochemistry. In 32 cases, amplification
of EGFR, c-erbB-2/neu, MDM-2, and c-myc was studied by Southern blot hybridization. The expression levels of these proteins
were correlated with HPV positivity, International Federation of Gynecologists and Obstetricians stage, lymph node metastases,
tumor diameter, vessel invasion, and disease-free and overall survival.
Moderate/strong expression of EGFR was observed in 54% of tumors. c-erbB-2/neu was focally positive in 12 cases. p53 showed
moderate/strong expression in 32% of the tumors. Thirteen % of tumors showed a moderate/strong expression of MDM-2, and this
expression was correlated to p53 expression ( P < 0.001). Only moderate/strong expression of EGFR was associated with reduced disease-free ( P = 0.002) and overall survival ( P = 0.003). In multivariate analysis, the association of EGFR overexpression with poor prognosis was independent from lymph
node status. Gene amplification was found for EGFR (four cases), c-erbB-2/neu (two cases), and c-myc (six cases). In two tumors,
rearrangement of c-myc was found, probably due to the integration of HPV.
In conclusion, overexpression of the EGFR is an independent predictor for prognosis in earlier stages (stage I and II) of
cervical cancer. p53 and MDM-2 expression are correlated to each other and may play a role in the interaction with HPV. The
importance of c-erbB-2/neu and c-myc amplification is relatively small in stage I and II cervical cancer. |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_69659671</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>69659671</sourcerecordid><originalsourceid>FETCH-LOGICAL-h267t-377a8b917bbff2d93b772e088339327479ecd67b3807e770e9b5b756b720826a3</originalsourceid><addsrcrecordid>eNpF0M1KxDAQB_AiiuvXK0gO4q2QNttO421ZdlUQVkTPJUmn20jb1Ez3w9fwiY244ilD5jcz8D-KzpIsg1ikeXYcag5FzKcinUTnRO-cJ9OET0-jScITzoHLs-hr1Ru3xh7ZrB3Rq9G6npjt2Vx5Y3vXKWKuZmOD7C30bYBz9Fu7v2OrLXrcDx6JwtCfWgy2Qt-plt17txsbtlRmdJ69oMHhp3gkNiNyxqoRK7azgTy78P_s3bp3ZOkyOqlVS3h1eC-it-Xidf4QP63uH-ezp7hJcxhjAaAKLRPQuq7TSgoNkCIvCiGkSGEKEk2VgxYFBwTgKHWmIcs1pLxIcyUuotvfvYN3HxuksewsGWxb1aPbUJnLPJM5JAFeH-BGd1iVg7ed8p_lX4oB3ByAIqPa2qveWPp3YYcs4P9gY9fNznosTYDoQ4IY0m7KrBRlBiC-AfHAiuo</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>69659671</pqid></control><display><type>article</type><title>Oncogene Alterations in Carcinomas of the Uterine Cervix: Overexpression of the Epidermal Growth Factor Receptor Is Associated with Poor Prognosis</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>KERSEMAEKERS, A.-M. F ; FLEUREN, G. J ; KENTER, G. G ; VAN DEN BROEK, L. J. C. M ; ULJEE, S. M ; HERMANS, J ; VAN DE VIJVER, M. J</creator><creatorcontrib>KERSEMAEKERS, A.-M. F ; FLEUREN, G. J ; KENTER, G. G ; VAN DEN BROEK, L. J. C. M ; ULJEE, S. M ; HERMANS, J ; VAN DE VIJVER, M. J</creatorcontrib><description>The involvement of human papillomavirus (HPV) in the development of carcinomas of the uterine cervix has been firmly established.
However, other genetic alterations also play an important role in the pathogenesis of cervical cancer. Therefore, we have
investigated the role of several (onco)genes in cervical carcinoma.
In tumors from 136 patients with stage I and II cancer of the uterine cervix, the expression of epidermal growth factor receptor
(EGFR), c-erbB-2/neu, p53, and murine double minute 2 (MDM-2) was studied using immunohistochemistry. In 32 cases, amplification
of EGFR, c-erbB-2/neu, MDM-2, and c-myc was studied by Southern blot hybridization. The expression levels of these proteins
were correlated with HPV positivity, International Federation of Gynecologists and Obstetricians stage, lymph node metastases,
tumor diameter, vessel invasion, and disease-free and overall survival.
Moderate/strong expression of EGFR was observed in 54% of tumors. c-erbB-2/neu was focally positive in 12 cases. p53 showed
moderate/strong expression in 32% of the tumors. Thirteen % of tumors showed a moderate/strong expression of MDM-2, and this
expression was correlated to p53 expression ( P < 0.001). Only moderate/strong expression of EGFR was associated with reduced disease-free ( P = 0.002) and overall survival ( P = 0.003). In multivariate analysis, the association of EGFR overexpression with poor prognosis was independent from lymph
node status. Gene amplification was found for EGFR (four cases), c-erbB-2/neu (two cases), and c-myc (six cases). In two tumors,
rearrangement of c-myc was found, probably due to the integration of HPV.
In conclusion, overexpression of the EGFR is an independent predictor for prognosis in earlier stages (stage I and II) of
cervical cancer. p53 and MDM-2 expression are correlated to each other and may play a role in the interaction with HPV. The
importance of c-erbB-2/neu and c-myc amplification is relatively small in stage I and II cervical cancer.</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 10100709</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Biomarkers, Tumor - biosynthesis ; Disease-Free Survival ; Female ; Female genital diseases ; Genes, erbB-2 - physiology ; Genes, myc - physiology ; Gynecology. Andrology. Obstetrics ; Humans ; Lymphatic Metastasis ; Medical sciences ; Middle Aged ; Mitotic Index ; Mutation ; Neoplasm Staging ; Nuclear Proteins ; Oncogene Proteins - biosynthesis ; Papillomaviridae - isolation & purification ; Prognosis ; Proto-Oncogene Proteins - biosynthesis ; Proto-Oncogene Proteins c-mdm2 ; Receptor, Epidermal Growth Factor - biosynthesis ; Tumor Suppressor Protein p53 - biosynthesis ; Tumors ; Uterine Cervical Neoplasms - diagnosis ; Uterine Cervical Neoplasms - metabolism ; Uterine Cervical Neoplasms - mortality ; Uterine Cervical Neoplasms - pathology</subject><ispartof>Clinical cancer research, 1999-03, Vol.5 (3), p.577-586</ispartof><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1713987$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10100709$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KERSEMAEKERS, A.-M. F</creatorcontrib><creatorcontrib>FLEUREN, G. J</creatorcontrib><creatorcontrib>KENTER, G. G</creatorcontrib><creatorcontrib>VAN DEN BROEK, L. J. C. M</creatorcontrib><creatorcontrib>ULJEE, S. M</creatorcontrib><creatorcontrib>HERMANS, J</creatorcontrib><creatorcontrib>VAN DE VIJVER, M. J</creatorcontrib><title>Oncogene Alterations in Carcinomas of the Uterine Cervix: Overexpression of the Epidermal Growth Factor Receptor Is Associated with Poor Prognosis</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>The involvement of human papillomavirus (HPV) in the development of carcinomas of the uterine cervix has been firmly established.
However, other genetic alterations also play an important role in the pathogenesis of cervical cancer. Therefore, we have
investigated the role of several (onco)genes in cervical carcinoma.
In tumors from 136 patients with stage I and II cancer of the uterine cervix, the expression of epidermal growth factor receptor
(EGFR), c-erbB-2/neu, p53, and murine double minute 2 (MDM-2) was studied using immunohistochemistry. In 32 cases, amplification
of EGFR, c-erbB-2/neu, MDM-2, and c-myc was studied by Southern blot hybridization. The expression levels of these proteins
were correlated with HPV positivity, International Federation of Gynecologists and Obstetricians stage, lymph node metastases,
tumor diameter, vessel invasion, and disease-free and overall survival.
Moderate/strong expression of EGFR was observed in 54% of tumors. c-erbB-2/neu was focally positive in 12 cases. p53 showed
moderate/strong expression in 32% of the tumors. Thirteen % of tumors showed a moderate/strong expression of MDM-2, and this
expression was correlated to p53 expression ( P < 0.001). Only moderate/strong expression of EGFR was associated with reduced disease-free ( P = 0.002) and overall survival ( P = 0.003). In multivariate analysis, the association of EGFR overexpression with poor prognosis was independent from lymph
node status. Gene amplification was found for EGFR (four cases), c-erbB-2/neu (two cases), and c-myc (six cases). In two tumors,
rearrangement of c-myc was found, probably due to the integration of HPV.
In conclusion, overexpression of the EGFR is an independent predictor for prognosis in earlier stages (stage I and II) of
cervical cancer. p53 and MDM-2 expression are correlated to each other and may play a role in the interaction with HPV. The
importance of c-erbB-2/neu and c-myc amplification is relatively small in stage I and II cervical cancer.</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - biosynthesis</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Genes, erbB-2 - physiology</subject><subject>Genes, myc - physiology</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Lymphatic Metastasis</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Mitotic Index</subject><subject>Mutation</subject><subject>Neoplasm Staging</subject><subject>Nuclear Proteins</subject><subject>Oncogene Proteins - biosynthesis</subject><subject>Papillomaviridae - isolation & purification</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins - biosynthesis</subject><subject>Proto-Oncogene Proteins c-mdm2</subject><subject>Receptor, Epidermal Growth Factor - biosynthesis</subject><subject>Tumor Suppressor Protein p53 - biosynthesis</subject><subject>Tumors</subject><subject>Uterine Cervical Neoplasms - diagnosis</subject><subject>Uterine Cervical Neoplasms - metabolism</subject><subject>Uterine Cervical Neoplasms - mortality</subject><subject>Uterine Cervical Neoplasms - pathology</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0M1KxDAQB_AiiuvXK0gO4q2QNttO421ZdlUQVkTPJUmn20jb1Ez3w9fwiY244ilD5jcz8D-KzpIsg1ikeXYcag5FzKcinUTnRO-cJ9OET0-jScITzoHLs-hr1Ru3xh7ZrB3Rq9G6npjt2Vx5Y3vXKWKuZmOD7C30bYBz9Fu7v2OrLXrcDx6JwtCfWgy2Qt-plt17txsbtlRmdJ69oMHhp3gkNiNyxqoRK7azgTy78P_s3bp3ZOkyOqlVS3h1eC-it-Xidf4QP63uH-ezp7hJcxhjAaAKLRPQuq7TSgoNkCIvCiGkSGEKEk2VgxYFBwTgKHWmIcs1pLxIcyUuotvfvYN3HxuksewsGWxb1aPbUJnLPJM5JAFeH-BGd1iVg7ed8p_lX4oB3ByAIqPa2qveWPp3YYcs4P9gY9fNznosTYDoQ4IY0m7KrBRlBiC-AfHAiuo</recordid><startdate>19990301</startdate><enddate>19990301</enddate><creator>KERSEMAEKERS, A.-M. F</creator><creator>FLEUREN, G. J</creator><creator>KENTER, G. G</creator><creator>VAN DEN BROEK, L. J. C. M</creator><creator>ULJEE, S. M</creator><creator>HERMANS, J</creator><creator>VAN DE VIJVER, M. J</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>19990301</creationdate><title>Oncogene Alterations in Carcinomas of the Uterine Cervix: Overexpression of the Epidermal Growth Factor Receptor Is Associated with Poor Prognosis</title><author>KERSEMAEKERS, A.-M. F ; FLEUREN, G. J ; KENTER, G. G ; VAN DEN BROEK, L. J. C. M ; ULJEE, S. M ; HERMANS, J ; VAN DE VIJVER, M. J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h267t-377a8b917bbff2d93b772e088339327479ecd67b3807e770e9b5b756b720826a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - biosynthesis</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Genes, erbB-2 - physiology</topic><topic>Genes, myc - physiology</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Lymphatic Metastasis</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Mitotic Index</topic><topic>Mutation</topic><topic>Neoplasm Staging</topic><topic>Nuclear Proteins</topic><topic>Oncogene Proteins - biosynthesis</topic><topic>Papillomaviridae - isolation & purification</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins - biosynthesis</topic><topic>Proto-Oncogene Proteins c-mdm2</topic><topic>Receptor, Epidermal Growth Factor - biosynthesis</topic><topic>Tumor Suppressor Protein p53 - biosynthesis</topic><topic>Tumors</topic><topic>Uterine Cervical Neoplasms - diagnosis</topic><topic>Uterine Cervical Neoplasms - metabolism</topic><topic>Uterine Cervical Neoplasms - mortality</topic><topic>Uterine Cervical Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KERSEMAEKERS, A.-M. F</creatorcontrib><creatorcontrib>FLEUREN, G. J</creatorcontrib><creatorcontrib>KENTER, G. G</creatorcontrib><creatorcontrib>VAN DEN BROEK, L. J. C. M</creatorcontrib><creatorcontrib>ULJEE, S. M</creatorcontrib><creatorcontrib>HERMANS, J</creatorcontrib><creatorcontrib>VAN DE VIJVER, M. J</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KERSEMAEKERS, A.-M. F</au><au>FLEUREN, G. J</au><au>KENTER, G. G</au><au>VAN DEN BROEK, L. J. C. M</au><au>ULJEE, S. M</au><au>HERMANS, J</au><au>VAN DE VIJVER, M. J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oncogene Alterations in Carcinomas of the Uterine Cervix: Overexpression of the Epidermal Growth Factor Receptor Is Associated with Poor Prognosis</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>1999-03-01</date><risdate>1999</risdate><volume>5</volume><issue>3</issue><spage>577</spage><epage>586</epage><pages>577-586</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>The involvement of human papillomavirus (HPV) in the development of carcinomas of the uterine cervix has been firmly established.
However, other genetic alterations also play an important role in the pathogenesis of cervical cancer. Therefore, we have
investigated the role of several (onco)genes in cervical carcinoma.
In tumors from 136 patients with stage I and II cancer of the uterine cervix, the expression of epidermal growth factor receptor
(EGFR), c-erbB-2/neu, p53, and murine double minute 2 (MDM-2) was studied using immunohistochemistry. In 32 cases, amplification
of EGFR, c-erbB-2/neu, MDM-2, and c-myc was studied by Southern blot hybridization. The expression levels of these proteins
were correlated with HPV positivity, International Federation of Gynecologists and Obstetricians stage, lymph node metastases,
tumor diameter, vessel invasion, and disease-free and overall survival.
Moderate/strong expression of EGFR was observed in 54% of tumors. c-erbB-2/neu was focally positive in 12 cases. p53 showed
moderate/strong expression in 32% of the tumors. Thirteen % of tumors showed a moderate/strong expression of MDM-2, and this
expression was correlated to p53 expression ( P < 0.001). Only moderate/strong expression of EGFR was associated with reduced disease-free ( P = 0.002) and overall survival ( P = 0.003). In multivariate analysis, the association of EGFR overexpression with poor prognosis was independent from lymph
node status. Gene amplification was found for EGFR (four cases), c-erbB-2/neu (two cases), and c-myc (six cases). In two tumors,
rearrangement of c-myc was found, probably due to the integration of HPV.
In conclusion, overexpression of the EGFR is an independent predictor for prognosis in earlier stages (stage I and II) of
cervical cancer. p53 and MDM-2 expression are correlated to each other and may play a role in the interaction with HPV. The
importance of c-erbB-2/neu and c-myc amplification is relatively small in stage I and II cervical cancer.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>10100709</pmid><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1078-0432 |
| ispartof | Clinical cancer research, 1999-03, Vol.5 (3), p.577-586 |
| issn | 1078-0432 1557-3265 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_69659671 |
| source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adult Aged Biological and medical sciences Biomarkers, Tumor - biosynthesis Disease-Free Survival Female Female genital diseases Genes, erbB-2 - physiology Genes, myc - physiology Gynecology. Andrology. Obstetrics Humans Lymphatic Metastasis Medical sciences Middle Aged Mitotic Index Mutation Neoplasm Staging Nuclear Proteins Oncogene Proteins - biosynthesis Papillomaviridae - isolation & purification Prognosis Proto-Oncogene Proteins - biosynthesis Proto-Oncogene Proteins c-mdm2 Receptor, Epidermal Growth Factor - biosynthesis Tumor Suppressor Protein p53 - biosynthesis Tumors Uterine Cervical Neoplasms - diagnosis Uterine Cervical Neoplasms - metabolism Uterine Cervical Neoplasms - mortality Uterine Cervical Neoplasms - pathology |
| title | Oncogene Alterations in Carcinomas of the Uterine Cervix: Overexpression of the Epidermal Growth Factor Receptor Is Associated with Poor Prognosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-03T10%3A50%3A48IST&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=Oncogene%20Alterations%20in%20Carcinomas%20of%20the%20Uterine%20Cervix:%20Overexpression%20of%20the%20Epidermal%20Growth%20Factor%20Receptor%20Is%20Associated%20with%20Poor%20Prognosis&rft.jtitle=Clinical%20cancer%20research&rft.au=KERSEMAEKERS,%20A.-M.%20F&rft.date=1999-03-01&rft.volume=5&rft.issue=3&rft.spage=577&rft.epage=586&rft.pages=577-586&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/&rft_dat=%3Cproquest_pubme%3E69659671%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=69659671&rft_id=info:pmid/10100709&rfr_iscdi=true |