PLAP expression is linked to invasive tumor growth in urothelial carcinoma of the bladder
Placental alkaline phosphatase (PLAP) is a protein with a poorly understood function that is normally only expressed in the placenta. In cancer, PLAP expression is a hallmark of germ cell neoplasms, but it can also occur in urothelial carcinoma. To evaluate the potential clinical significance of PLA...
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| creator | Plage, Henning Furlano, Kira Hofbauer, Sebastian Roßner, Florian Schallenberg, Simon Elezkurtaj, Sefer Lennartz, Maximilian Marx, Andreas Samtleben, Henrik Fisch, Margit Rink, Michael Slojewski, Marcin Kaczmarek, Krystian Ecke, Thorsten Klatte, Tobias Koch, Stefan Adamini, Nico Minner, Sarah Simon, Ronald Sauter, Guido Weischenfeldt, Joachim Schlomm, Thorsten Horst, David Zecha, Henrik Kluth, Martina Weinberger, Sarah |
| description | Placental alkaline phosphatase (PLAP) is a protein with a poorly understood function that is normally only expressed in the placenta. In cancer, PLAP expression is a hallmark of germ cell neoplasms, but it can also occur in urothelial carcinoma. To evaluate the potential clinical significance of PLAP expression in bladder cancer, METHODS: PLAP protein was analyzed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format.
PLAP staining was absent in normal urothelial cells but was observed in 15.9% of urothelial carcinomas, including 282 (11.5%) with weak, 57 (2.3%) with moderate, and 51 (2.1%) with strong staining. PLAP positivity occurred in 4.1% of 413 pTa G2 low-grade, 10.2% of 176 pTa G2 high-grade, and 7.2% of 97 pTa G3 tumors (p = 0.0636). As compared to pTa tumors, the PLAP positivity rate was markedly higher in 1341 pT2-4 carcinomas (19.8%, p 0.25). However, PLAP positivity was linked to p16 positivity (p = 0.0185), GATA3 positivity (p |
| doi_str_mv | 10.1007/s11255-024-04319-8 |
| format | Article |
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PLAP staining was absent in normal urothelial cells but was observed in 15.9% of urothelial carcinomas, including 282 (11.5%) with weak, 57 (2.3%) with moderate, and 51 (2.1%) with strong staining. PLAP positivity occurred in 4.1% of 413 pTa G2 low-grade, 10.2% of 176 pTa G2 high-grade, and 7.2% of 97 pTa G3 tumors (p = 0.0636). As compared to pTa tumors, the PLAP positivity rate was markedly higher in 1341 pT2-4 carcinomas (19.8%, p < 0.0001). Within pT2-4 carcinomas, PLAP staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence-free survival, and cancer-specific survival (p > 0.25). However, PLAP positivity was linked to p16 positivity (p = 0.0185), GATA3 positivity (p < 0.0001), and p63 expression loss (p = 0.0456).
In summary, these data show that PLAP is expressed in a significant fraction of pT2-4 urothelial carcinomas, unrelated to cancer aggressiveness but associated with specific molecular features. Once anti-PLAP cancer drugs become effective, urothelial carcinoma is a candidate tumor entity for clinical evaluation.</description><identifier>ISSN: 1573-2584</identifier><identifier>EISSN: 1573-2584</identifier><identifier>DOI: 10.1007/s11255-024-04319-8</identifier><identifier>PMID: 39680294</identifier><language>eng</language><publisher>Netherlands</publisher><ispartof>International urology and nephrology, 2024-12</ispartof><rights>2024. The Author(s).</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c184t-933447523898547d8b1d316f4ac3e27808faad277cc35d9cfb2176c67b74a44d3</cites><orcidid>0000-0002-7680-1870</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39680294$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Plage, Henning</creatorcontrib><creatorcontrib>Furlano, Kira</creatorcontrib><creatorcontrib>Hofbauer, Sebastian</creatorcontrib><creatorcontrib>Roßner, Florian</creatorcontrib><creatorcontrib>Schallenberg, Simon</creatorcontrib><creatorcontrib>Elezkurtaj, Sefer</creatorcontrib><creatorcontrib>Lennartz, Maximilian</creatorcontrib><creatorcontrib>Marx, Andreas</creatorcontrib><creatorcontrib>Samtleben, Henrik</creatorcontrib><creatorcontrib>Fisch, Margit</creatorcontrib><creatorcontrib>Rink, Michael</creatorcontrib><creatorcontrib>Slojewski, Marcin</creatorcontrib><creatorcontrib>Kaczmarek, Krystian</creatorcontrib><creatorcontrib>Ecke, Thorsten</creatorcontrib><creatorcontrib>Klatte, Tobias</creatorcontrib><creatorcontrib>Koch, Stefan</creatorcontrib><creatorcontrib>Adamini, Nico</creatorcontrib><creatorcontrib>Minner, Sarah</creatorcontrib><creatorcontrib>Simon, Ronald</creatorcontrib><creatorcontrib>Sauter, Guido</creatorcontrib><creatorcontrib>Weischenfeldt, Joachim</creatorcontrib><creatorcontrib>Schlomm, Thorsten</creatorcontrib><creatorcontrib>Horst, David</creatorcontrib><creatorcontrib>Zecha, Henrik</creatorcontrib><creatorcontrib>Kluth, Martina</creatorcontrib><creatorcontrib>Weinberger, Sarah</creatorcontrib><title>PLAP expression is linked to invasive tumor growth in urothelial carcinoma of the bladder</title><title>International urology and nephrology</title><addtitle>Int Urol Nephrol</addtitle><description>Placental alkaline phosphatase (PLAP) is a protein with a poorly understood function that is normally only expressed in the placenta. In cancer, PLAP expression is a hallmark of germ cell neoplasms, but it can also occur in urothelial carcinoma. To evaluate the potential clinical significance of PLAP expression in bladder cancer, METHODS: PLAP protein was analyzed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format.
PLAP staining was absent in normal urothelial cells but was observed in 15.9% of urothelial carcinomas, including 282 (11.5%) with weak, 57 (2.3%) with moderate, and 51 (2.1%) with strong staining. PLAP positivity occurred in 4.1% of 413 pTa G2 low-grade, 10.2% of 176 pTa G2 high-grade, and 7.2% of 97 pTa G3 tumors (p = 0.0636). As compared to pTa tumors, the PLAP positivity rate was markedly higher in 1341 pT2-4 carcinomas (19.8%, p < 0.0001). Within pT2-4 carcinomas, PLAP staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence-free survival, and cancer-specific survival (p > 0.25). However, PLAP positivity was linked to p16 positivity (p = 0.0185), GATA3 positivity (p < 0.0001), and p63 expression loss (p = 0.0456).
In summary, these data show that PLAP is expressed in a significant fraction of pT2-4 urothelial carcinomas, unrelated to cancer aggressiveness but associated with specific molecular features. Once anti-PLAP cancer drugs become effective, urothelial carcinoma is a candidate tumor entity for clinical evaluation.</description><issn>1573-2584</issn><issn>1573-2584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpNkDtPwzAAhC0EoqXwBxiQR5aAn7EzVhUvKRIdYGCyHNuhhiQudlLg3xNoQUx3Ot3d8AFwitEFRkhcJowJ5xkiLEOM4iKTe2CKuaAZ4ZLt__MTcJTSC0KokAgdggktcolIwabgaVnOl9B9rKNLyYcO-gQb3706C_sAfbfRyW8c7Ic2RPgcw3u_GlM4xNCvXON1A42Oxneh1TDUcAxh1WhrXTwGB7VukjvZ6Qw8Xl89LG6z8v7mbjEvM4Ml67OCUsYEJ1QWkjNhZYUtxXnNtKGOCIlkrbUlQhhDuS1MXREscpOLSjDNmKUzcL79XcfwNrjUq9Yn45pGdy4MSVHMcslzROlYJduqiSGl6Gq1jr7V8VNhpL6Rqi1SNSJVP0iVHEdnu_-hap39m_wypF8RkHFl</recordid><startdate>20241216</startdate><enddate>20241216</enddate><creator>Plage, Henning</creator><creator>Furlano, Kira</creator><creator>Hofbauer, Sebastian</creator><creator>Roßner, Florian</creator><creator>Schallenberg, Simon</creator><creator>Elezkurtaj, Sefer</creator><creator>Lennartz, Maximilian</creator><creator>Marx, Andreas</creator><creator>Samtleben, Henrik</creator><creator>Fisch, Margit</creator><creator>Rink, Michael</creator><creator>Slojewski, Marcin</creator><creator>Kaczmarek, Krystian</creator><creator>Ecke, Thorsten</creator><creator>Klatte, Tobias</creator><creator>Koch, Stefan</creator><creator>Adamini, Nico</creator><creator>Minner, Sarah</creator><creator>Simon, Ronald</creator><creator>Sauter, Guido</creator><creator>Weischenfeldt, Joachim</creator><creator>Schlomm, Thorsten</creator><creator>Horst, David</creator><creator>Zecha, Henrik</creator><creator>Kluth, Martina</creator><creator>Weinberger, Sarah</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7680-1870</orcidid></search><sort><creationdate>20241216</creationdate><title>PLAP expression is linked to invasive tumor growth in urothelial carcinoma of the bladder</title><author>Plage, Henning ; Furlano, Kira ; Hofbauer, Sebastian ; Roßner, Florian ; Schallenberg, Simon ; Elezkurtaj, Sefer ; Lennartz, Maximilian ; Marx, Andreas ; Samtleben, Henrik ; Fisch, Margit ; Rink, Michael ; Slojewski, Marcin ; Kaczmarek, Krystian ; Ecke, Thorsten ; Klatte, Tobias ; Koch, Stefan ; Adamini, Nico ; Minner, Sarah ; Simon, Ronald ; Sauter, Guido ; Weischenfeldt, Joachim ; Schlomm, Thorsten ; Horst, David ; Zecha, Henrik ; Kluth, Martina ; Weinberger, Sarah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c184t-933447523898547d8b1d316f4ac3e27808faad277cc35d9cfb2176c67b74a44d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Plage, Henning</creatorcontrib><creatorcontrib>Furlano, Kira</creatorcontrib><creatorcontrib>Hofbauer, Sebastian</creatorcontrib><creatorcontrib>Roßner, Florian</creatorcontrib><creatorcontrib>Schallenberg, Simon</creatorcontrib><creatorcontrib>Elezkurtaj, Sefer</creatorcontrib><creatorcontrib>Lennartz, Maximilian</creatorcontrib><creatorcontrib>Marx, Andreas</creatorcontrib><creatorcontrib>Samtleben, Henrik</creatorcontrib><creatorcontrib>Fisch, Margit</creatorcontrib><creatorcontrib>Rink, Michael</creatorcontrib><creatorcontrib>Slojewski, Marcin</creatorcontrib><creatorcontrib>Kaczmarek, Krystian</creatorcontrib><creatorcontrib>Ecke, Thorsten</creatorcontrib><creatorcontrib>Klatte, Tobias</creatorcontrib><creatorcontrib>Koch, Stefan</creatorcontrib><creatorcontrib>Adamini, Nico</creatorcontrib><creatorcontrib>Minner, Sarah</creatorcontrib><creatorcontrib>Simon, Ronald</creatorcontrib><creatorcontrib>Sauter, Guido</creatorcontrib><creatorcontrib>Weischenfeldt, Joachim</creatorcontrib><creatorcontrib>Schlomm, Thorsten</creatorcontrib><creatorcontrib>Horst, David</creatorcontrib><creatorcontrib>Zecha, Henrik</creatorcontrib><creatorcontrib>Kluth, Martina</creatorcontrib><creatorcontrib>Weinberger, Sarah</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International urology and nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Plage, Henning</au><au>Furlano, Kira</au><au>Hofbauer, Sebastian</au><au>Roßner, Florian</au><au>Schallenberg, Simon</au><au>Elezkurtaj, Sefer</au><au>Lennartz, Maximilian</au><au>Marx, Andreas</au><au>Samtleben, Henrik</au><au>Fisch, Margit</au><au>Rink, Michael</au><au>Slojewski, Marcin</au><au>Kaczmarek, Krystian</au><au>Ecke, Thorsten</au><au>Klatte, Tobias</au><au>Koch, Stefan</au><au>Adamini, Nico</au><au>Minner, Sarah</au><au>Simon, Ronald</au><au>Sauter, Guido</au><au>Weischenfeldt, Joachim</au><au>Schlomm, Thorsten</au><au>Horst, David</au><au>Zecha, Henrik</au><au>Kluth, Martina</au><au>Weinberger, Sarah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PLAP expression is linked to invasive tumor growth in urothelial carcinoma of the bladder</atitle><jtitle>International urology and nephrology</jtitle><addtitle>Int Urol Nephrol</addtitle><date>2024-12-16</date><risdate>2024</risdate><issn>1573-2584</issn><eissn>1573-2584</eissn><abstract>Placental alkaline phosphatase (PLAP) is a protein with a poorly understood function that is normally only expressed in the placenta. In cancer, PLAP expression is a hallmark of germ cell neoplasms, but it can also occur in urothelial carcinoma. To evaluate the potential clinical significance of PLAP expression in bladder cancer, METHODS: PLAP protein was analyzed by immunohistochemistry in more than 2500 urothelial bladder carcinomas in a tissue microarray format.
PLAP staining was absent in normal urothelial cells but was observed in 15.9% of urothelial carcinomas, including 282 (11.5%) with weak, 57 (2.3%) with moderate, and 51 (2.1%) with strong staining. PLAP positivity occurred in 4.1% of 413 pTa G2 low-grade, 10.2% of 176 pTa G2 high-grade, and 7.2% of 97 pTa G3 tumors (p = 0.0636). As compared to pTa tumors, the PLAP positivity rate was markedly higher in 1341 pT2-4 carcinomas (19.8%, p < 0.0001). Within pT2-4 carcinomas, PLAP staining was unrelated to pT, pN, grade, L-status, V-status, overall survival, recurrence-free survival, and cancer-specific survival (p > 0.25). However, PLAP positivity was linked to p16 positivity (p = 0.0185), GATA3 positivity (p < 0.0001), and p63 expression loss (p = 0.0456).
In summary, these data show that PLAP is expressed in a significant fraction of pT2-4 urothelial carcinomas, unrelated to cancer aggressiveness but associated with specific molecular features. Once anti-PLAP cancer drugs become effective, urothelial carcinoma is a candidate tumor entity for clinical evaluation.</abstract><cop>Netherlands</cop><pmid>39680294</pmid><doi>10.1007/s11255-024-04319-8</doi><orcidid>https://orcid.org/0000-0002-7680-1870</orcidid></addata></record> |
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| title | PLAP expression is linked to invasive tumor growth in urothelial carcinoma of the bladder |
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