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P21Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis
Human papillomavirus is involved in the carcinogenesis of tonsillar squamous cell carcinomas. Here, we investigated the expression and the prognostic value of key cell cycle proteins in the pRb and p53 pathways in both human papillomavirus type 16-positive and -negative tonsillar squamous cell carci...
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| Published in: | Modern pathology 2009-05, Vol.22 (5), p.686-698 |
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| creator | Hafkamp, Harriët C Mooren, Jeroen J Claessen, Sandra MH Klingenberg, Boris Voogd, Adri C Bot, Fredrik J Klussmann, J Peter Hopman, Anton HN Manni, Johannes J Kremer, Bernd Ramaekers, Frans CS Speel, Ernst-Jan M |
| description | Human papillomavirus is involved in the carcinogenesis of tonsillar squamous cell carcinomas. Here, we investigated the expression and the prognostic value of key cell cycle proteins in the pRb and p53 pathways in both human papillomavirus type 16-positive and -negative tonsillar squamous cell carcinomas. Using immunohistochemistry, 77 tonsillar squamous cell carcinomas with known human papillomavirus type 16 status and clinical outcome were analyzed for expression of Ki67, p16
INK4A,
cyclin D1, pRb, p14
ARF
, MDM2, p53, p21
Cip1/WAF1
, and p27
KIP1
. Results were correlated with each other and with clinical and demographic patient data. A total of 35% of tonsillar carcinomas harbored integrated human papillomavirus type 16 DNA and p16
INK4A
overexpression, both being considered essential features for human papillomavirus association. These tumors also showed the overexpression of p14
ARF
(
P |
| doi_str_mv | 10.1038/modpathol.2009.23 |
| format | article |
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INK4A,
cyclin D1, pRb, p14
ARF
, MDM2, p53, p21
Cip1/WAF1
, and p27
KIP1
. Results were correlated with each other and with clinical and demographic patient data. A total of 35% of tonsillar carcinomas harbored integrated human papillomavirus type 16 DNA and p16
INK4A
overexpression, both being considered essential features for human papillomavirus association. These tumors also showed the overexpression of p14
ARF
(
P
<0.0001) and p21
Cip1/WAF1
(
P
=0.001), and downregulation of pRb (
P
<0.0001) and cyclin D1 (
P
=0.027) compared with the human papillomavirus-negative cases. Univariate Cox regression analyses revealed a favorable survival rate for non-smokers (
P
=0.006), as well as for patients with T1-2 tumors (
P
<0.0001) or tumors showing low expression of cyclin D1 (
P
=0.028), presence of human papillomavirus and overexpression of p16
INK4A
(
P
=0.01), p14
ARF
(
P
=0.02) or p21
Cip1/WAF1
(
P
=0.004). In multivariate regression analyses, smoking and tumor size, as well as expression of cyclin D1 and p21
Cip1/WAF1
, were found to be independent prognostic markers. We conclude that human papillomavirus positivity in tonsillar squamous cell carcinomas strongly correlates with p21
Cip1/WAF1
and p14
ARF
overexpression and downregulation of pRb and cyclin D1. In particular p21
Cip1/WAF1
overexpression is an excellent favorable prognosticator in tonsillar squamous cell carcinomas.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2009.23</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Cancer ; Cell cycle ; Developmental biology ; Human papillomavirus ; Laboratory Medicine ; Medical prognosis ; Medicine ; Medicine & Public Health ; Oncology ; original-article ; Otolaryngology ; Pathology ; Protein expression ; Proteins ; Regression analysis ; Smoking ; Tumors</subject><ispartof>Modern pathology, 2009-05, Vol.22 (5), p.686-698</ispartof><rights>United States and Canadian Academy of Pathology, Inc. 2009</rights><rights>Copyright Nature Publishing Group May 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1603-106be6b0c1f30b04a3a679cc3ca3bb163d00c03f0522db79a3fc0d04bcee17dd3</citedby><cites>FETCH-LOGICAL-c1603-106be6b0c1f30b04a3a679cc3ca3bb163d00c03f0522db79a3fc0d04bcee17dd3</cites></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></links><search><creatorcontrib>Hafkamp, Harriët C</creatorcontrib><creatorcontrib>Mooren, Jeroen J</creatorcontrib><creatorcontrib>Claessen, Sandra MH</creatorcontrib><creatorcontrib>Klingenberg, Boris</creatorcontrib><creatorcontrib>Voogd, Adri C</creatorcontrib><creatorcontrib>Bot, Fredrik J</creatorcontrib><creatorcontrib>Klussmann, J Peter</creatorcontrib><creatorcontrib>Hopman, Anton HN</creatorcontrib><creatorcontrib>Manni, Johannes J</creatorcontrib><creatorcontrib>Kremer, Bernd</creatorcontrib><creatorcontrib>Ramaekers, Frans CS</creatorcontrib><creatorcontrib>Speel, Ernst-Jan M</creatorcontrib><title>P21Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><description>Human papillomavirus is involved in the carcinogenesis of tonsillar squamous cell carcinomas. Here, we investigated the expression and the prognostic value of key cell cycle proteins in the pRb and p53 pathways in both human papillomavirus type 16-positive and -negative tonsillar squamous cell carcinomas. Using immunohistochemistry, 77 tonsillar squamous cell carcinomas with known human papillomavirus type 16 status and clinical outcome were analyzed for expression of Ki67, p16
INK4A,
cyclin D1, pRb, p14
ARF
, MDM2, p53, p21
Cip1/WAF1
, and p27
KIP1
. Results were correlated with each other and with clinical and demographic patient data. A total of 35% of tonsillar carcinomas harbored integrated human papillomavirus type 16 DNA and p16
INK4A
overexpression, both being considered essential features for human papillomavirus association. These tumors also showed the overexpression of p14
ARF
(
P
<0.0001) and p21
Cip1/WAF1
(
P
=0.001), and downregulation of pRb (
P
<0.0001) and cyclin D1 (
P
=0.027) compared with the human papillomavirus-negative cases. Univariate Cox regression analyses revealed a favorable survival rate for non-smokers (
P
=0.006), as well as for patients with T1-2 tumors (
P
<0.0001) or tumors showing low expression of cyclin D1 (
P
=0.028), presence of human papillomavirus and overexpression of p16
INK4A
(
P
=0.01), p14
ARF
(
P
=0.02) or p21
Cip1/WAF1
(
P
=0.004). In multivariate regression analyses, smoking and tumor size, as well as expression of cyclin D1 and p21
Cip1/WAF1
, were found to be independent prognostic markers. We conclude that human papillomavirus positivity in tonsillar squamous cell carcinomas strongly correlates with p21
Cip1/WAF1
and p14
ARF
overexpression and downregulation of pRb and cyclin D1. In particular p21
Cip1/WAF1
overexpression is an excellent favorable prognosticator in tonsillar squamous cell carcinomas.</description><subject>Cancer</subject><subject>Cell cycle</subject><subject>Developmental biology</subject><subject>Human papillomavirus</subject><subject>Laboratory Medicine</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>original-article</subject><subject>Otolaryngology</subject><subject>Pathology</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Regression analysis</subject><subject>Smoking</subject><subject>Tumors</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNp1kD1PwzAURS0EEqXwA9gs9rTPdpImY1VRilSJDnyM1rPjtK5SO9ih0H9PqiKYmO5yzr3SJeSWwYiBKMY7X7XYbXwz4gDliIszMmCZgAR4kZ2TARSlSESZ8UtyFeMWgKVZwQfErTib2ZaN36ZzRs1XG0yM1jtqI41d8G7dHCjG6LXFzlT003Ybuli9Jq2PtrN7Qzvvom0aDFRj0Nb5HVJ0FUVa494HVI2hbfBr1wvxmlzU2ERz85ND8jK_f54tkuXTw-Nsukw0y0EkDHJlcgWa1QIUpCgwn5RaC41CKZaLCkCDqCHjvFKTEkWtoYJUaWPYpKrEkNydevvl9w8TO7n1H8H1k5JzxrKiSEUPsROkg48xmFq2we4wHCQDeXxV_r4qj69KfnT4yYk969Ym_BX_L30DduiACw</recordid><startdate>20090501</startdate><enddate>20090501</enddate><creator>Hafkamp, Harriët C</creator><creator>Mooren, Jeroen J</creator><creator>Claessen, Sandra MH</creator><creator>Klingenberg, Boris</creator><creator>Voogd, Adri C</creator><creator>Bot, Fredrik J</creator><creator>Klussmann, J Peter</creator><creator>Hopman, Anton HN</creator><creator>Manni, Johannes J</creator><creator>Kremer, Bernd</creator><creator>Ramaekers, Frans CS</creator><creator>Speel, Ernst-Jan M</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20090501</creationdate><title>P21Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis</title><author>Hafkamp, Harriët C ; Mooren, Jeroen J ; Claessen, Sandra MH ; Klingenberg, Boris ; Voogd, Adri C ; Bot, Fredrik J ; Klussmann, J Peter ; Hopman, Anton HN ; Manni, Johannes J ; Kremer, Bernd ; Ramaekers, Frans CS ; Speel, Ernst-Jan M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1603-106be6b0c1f30b04a3a679cc3ca3bb163d00c03f0522db79a3fc0d04bcee17dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Cancer</topic><topic>Cell cycle</topic><topic>Developmental biology</topic><topic>Human papillomavirus</topic><topic>Laboratory Medicine</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>original-article</topic><topic>Otolaryngology</topic><topic>Pathology</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Regression analysis</topic><topic>Smoking</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hafkamp, Harriët C</creatorcontrib><creatorcontrib>Mooren, Jeroen J</creatorcontrib><creatorcontrib>Claessen, Sandra MH</creatorcontrib><creatorcontrib>Klingenberg, Boris</creatorcontrib><creatorcontrib>Voogd, Adri C</creatorcontrib><creatorcontrib>Bot, Fredrik J</creatorcontrib><creatorcontrib>Klussmann, J Peter</creatorcontrib><creatorcontrib>Hopman, Anton HN</creatorcontrib><creatorcontrib>Manni, Johannes J</creatorcontrib><creatorcontrib>Kremer, Bernd</creatorcontrib><creatorcontrib>Ramaekers, Frans CS</creatorcontrib><creatorcontrib>Speel, Ernst-Jan M</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</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)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</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>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Biological Science Journals</collection><collection>Nursing & Allied Health Premium</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><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hafkamp, Harriët C</au><au>Mooren, Jeroen J</au><au>Claessen, Sandra MH</au><au>Klingenberg, Boris</au><au>Voogd, Adri C</au><au>Bot, Fredrik J</au><au>Klussmann, J Peter</au><au>Hopman, Anton HN</au><au>Manni, Johannes J</au><au>Kremer, Bernd</au><au>Ramaekers, Frans CS</au><au>Speel, Ernst-Jan M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>P21Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><date>2009-05-01</date><risdate>2009</risdate><volume>22</volume><issue>5</issue><spage>686</spage><epage>698</epage><pages>686-698</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><abstract>Human papillomavirus is involved in the carcinogenesis of tonsillar squamous cell carcinomas. Here, we investigated the expression and the prognostic value of key cell cycle proteins in the pRb and p53 pathways in both human papillomavirus type 16-positive and -negative tonsillar squamous cell carcinomas. Using immunohistochemistry, 77 tonsillar squamous cell carcinomas with known human papillomavirus type 16 status and clinical outcome were analyzed for expression of Ki67, p16
INK4A,
cyclin D1, pRb, p14
ARF
, MDM2, p53, p21
Cip1/WAF1
, and p27
KIP1
. Results were correlated with each other and with clinical and demographic patient data. A total of 35% of tonsillar carcinomas harbored integrated human papillomavirus type 16 DNA and p16
INK4A
overexpression, both being considered essential features for human papillomavirus association. These tumors also showed the overexpression of p14
ARF
(
P
<0.0001) and p21
Cip1/WAF1
(
P
=0.001), and downregulation of pRb (
P
<0.0001) and cyclin D1 (
P
=0.027) compared with the human papillomavirus-negative cases. Univariate Cox regression analyses revealed a favorable survival rate for non-smokers (
P
=0.006), as well as for patients with T1-2 tumors (
P
<0.0001) or tumors showing low expression of cyclin D1 (
P
=0.028), presence of human papillomavirus and overexpression of p16
INK4A
(
P
=0.01), p14
ARF
(
P
=0.02) or p21
Cip1/WAF1
(
P
=0.004). In multivariate regression analyses, smoking and tumor size, as well as expression of cyclin D1 and p21
Cip1/WAF1
, were found to be independent prognostic markers. We conclude that human papillomavirus positivity in tonsillar squamous cell carcinomas strongly correlates with p21
Cip1/WAF1
and p14
ARF
overexpression and downregulation of pRb and cyclin D1. In particular p21
Cip1/WAF1
overexpression is an excellent favorable prognosticator in tonsillar squamous cell carcinomas.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><doi>10.1038/modpathol.2009.23</doi><tpages>13</tpages></addata></record> |
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| ispartof | Modern pathology, 2009-05, Vol.22 (5), p.686-698 |
| issn | 0893-3952 1530-0285 |
| language | eng |
| recordid | cdi_proquest_journals_221158843 |
| source | Nature |
| subjects | Cancer Cell cycle Developmental biology Human papillomavirus Laboratory Medicine Medical prognosis Medicine Medicine & Public Health Oncology original-article Otolaryngology Pathology Protein expression Proteins Regression analysis Smoking Tumors |
| title | P21Cip1/WAF1 expression is strongly associated with HPV-positive tonsillar carcinoma and a favorable prognosis |
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