Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer
Background Kallikrein‐related peptidase 2 (KLK2)—like KLK3 (prostate‐specific antigen [PSA])—belongs to the highly conserved serine proteases of the glandular kallikrein protein family (KLK family). Studies suggested that measurement of KLK2 serum levels advanced the predictive accuracy of PSA testi...
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| Veröffentlicht in: | The Prostate 2020-09, Vol.80 (13), p.1097-1107 |
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| creator | Bonk, Sarah Kluth, Martina Jansen, Kristina Hube‐Magg, Claudia Makrypidi‐Fraune, Georgia Höflmayer, Doris Weidemann, Sören Möller, Katharina Uhlig, Ria Büscheck, Franziska Luebke, Andreas M. Burandt, Eike Clauditz, Till S. Steurer, Stefan Schlomm, Thorsten Huland, Hartwig Heinzer, Hans Sauter, Guido Simon, Ronald Dum, David |
| description | Background
Kallikrein‐related peptidase 2 (KLK2)—like KLK3 (prostate‐specific antigen [PSA])—belongs to the highly conserved serine proteases of the glandular kallikrein protein family (KLK family). Studies suggested that measurement of KLK2 serum levels advanced the predictive accuracy of PSA testing in prostate cancer.
Methods
To clarify the potential utility of KLK2 as a prognostic tissue biomarker, KLK2 expression was analyzed by immunohistochemistry in more than 12 000 prostate cancers.
Results
Normal epithelium cells usually showed weak to moderate KLK2 immunostaining, whereas KLK2 was negative in 23%, weak in 38%, moderate in 35%, and strong in 4% of 9576 analyzable cancers. Lost or reduced KLK2 immunostaining was associated with advanced tumor stage, high Gleason score, lymph node metastasis, increased cell proliferation, positive resection margin, and early PSA recurrence (P |
| doi_str_mv | 10.1002/pros.24038 |
| format | Article |
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Kallikrein‐related peptidase 2 (KLK2)—like KLK3 (prostate‐specific antigen [PSA])—belongs to the highly conserved serine proteases of the glandular kallikrein protein family (KLK family). Studies suggested that measurement of KLK2 serum levels advanced the predictive accuracy of PSA testing in prostate cancer.
Methods
To clarify the potential utility of KLK2 as a prognostic tissue biomarker, KLK2 expression was analyzed by immunohistochemistry in more than 12 000 prostate cancers.
Results
Normal epithelium cells usually showed weak to moderate KLK2 immunostaining, whereas KLK2 was negative in 23%, weak in 38%, moderate in 35%, and strong in 4% of 9576 analyzable cancers. Lost or reduced KLK2 immunostaining was associated with advanced tumor stage, high Gleason score, lymph node metastasis, increased cell proliferation, positive resection margin, and early PSA recurrence (P < .0001). Comparison with previously analyzed molecular alterations revealed a strong association of KLK2 loss and presence of TMPRSS2:ERG fusion (P < .0001), most of all analyzed common deletions (9 of 11; P ≤ .03), and decreased PSA immunostaining (P < .0001 each). Cancers with combined negative or weak immunostaining of KLK2 and PSA showed worse prognosis than cancers with at least moderate staining of one or both proteins (P < .0001). Multivariate analyses including established preoperative and postoperative prognostic parameters showed a strong independent prognostic impact of KLK2 loss alone or in combination of PSA, especially in erythroblast transformation‐specific‐negative cancers (P ≤ .006).
Conclusions
Loss of KLK2 expression is a potentially useful prognostic marker in prostate cancer. Analysis of KLK2 alone or in combination with PSA may be useful for estimating cancer aggressiveness at the time of biopsy.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.24038</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc</publisher><subject>Biopsy ; Cell proliferation ; Epithelium ; Immunohistochemistry ; Kallikrein ; Lymph nodes ; Metastases ; Peptidase ; Prognosis ; Prostate cancer ; PSA ; Serine ; Serum levels ; tissue micro array</subject><ispartof>The Prostate, 2020-09, Vol.80 (13), p.1097-1107</ispartof><rights>2020 The Authors. published by Wiley Periodicals LLC</rights><rights>2020. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3708-ef3d1686e8c4a2a92bee98a8458bbdd87c24c51a7f261e5d244c306beb30b41d3</citedby><cites>FETCH-LOGICAL-c3708-ef3d1686e8c4a2a92bee98a8458bbdd87c24c51a7f261e5d244c306beb30b41d3</cites><orcidid>0000-0003-0158-4258</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.24038$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.24038$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids></links><search><creatorcontrib>Bonk, Sarah</creatorcontrib><creatorcontrib>Kluth, Martina</creatorcontrib><creatorcontrib>Jansen, Kristina</creatorcontrib><creatorcontrib>Hube‐Magg, Claudia</creatorcontrib><creatorcontrib>Makrypidi‐Fraune, Georgia</creatorcontrib><creatorcontrib>Höflmayer, Doris</creatorcontrib><creatorcontrib>Weidemann, Sören</creatorcontrib><creatorcontrib>Möller, Katharina</creatorcontrib><creatorcontrib>Uhlig, Ria</creatorcontrib><creatorcontrib>Büscheck, Franziska</creatorcontrib><creatorcontrib>Luebke, Andreas M.</creatorcontrib><creatorcontrib>Burandt, Eike</creatorcontrib><creatorcontrib>Clauditz, Till S.</creatorcontrib><creatorcontrib>Steurer, Stefan</creatorcontrib><creatorcontrib>Schlomm, Thorsten</creatorcontrib><creatorcontrib>Huland, Hartwig</creatorcontrib><creatorcontrib>Heinzer, Hans</creatorcontrib><creatorcontrib>Sauter, Guido</creatorcontrib><creatorcontrib>Simon, Ronald</creatorcontrib><creatorcontrib>Dum, David</creatorcontrib><title>Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer</title><title>The Prostate</title><description>Background
Kallikrein‐related peptidase 2 (KLK2)—like KLK3 (prostate‐specific antigen [PSA])—belongs to the highly conserved serine proteases of the glandular kallikrein protein family (KLK family). Studies suggested that measurement of KLK2 serum levels advanced the predictive accuracy of PSA testing in prostate cancer.
Methods
To clarify the potential utility of KLK2 as a prognostic tissue biomarker, KLK2 expression was analyzed by immunohistochemistry in more than 12 000 prostate cancers.
Results
Normal epithelium cells usually showed weak to moderate KLK2 immunostaining, whereas KLK2 was negative in 23%, weak in 38%, moderate in 35%, and strong in 4% of 9576 analyzable cancers. Lost or reduced KLK2 immunostaining was associated with advanced tumor stage, high Gleason score, lymph node metastasis, increased cell proliferation, positive resection margin, and early PSA recurrence (P < .0001). Comparison with previously analyzed molecular alterations revealed a strong association of KLK2 loss and presence of TMPRSS2:ERG fusion (P < .0001), most of all analyzed common deletions (9 of 11; P ≤ .03), and decreased PSA immunostaining (P < .0001 each). Cancers with combined negative or weak immunostaining of KLK2 and PSA showed worse prognosis than cancers with at least moderate staining of one or both proteins (P < .0001). Multivariate analyses including established preoperative and postoperative prognostic parameters showed a strong independent prognostic impact of KLK2 loss alone or in combination of PSA, especially in erythroblast transformation‐specific‐negative cancers (P ≤ .006).
Conclusions
Loss of KLK2 expression is a potentially useful prognostic marker in prostate cancer. Analysis of KLK2 alone or in combination with PSA may be useful for estimating cancer aggressiveness at the time of biopsy.</description><subject>Biopsy</subject><subject>Cell proliferation</subject><subject>Epithelium</subject><subject>Immunohistochemistry</subject><subject>Kallikrein</subject><subject>Lymph nodes</subject><subject>Metastases</subject><subject>Peptidase</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>PSA</subject><subject>Serine</subject><subject>Serum levels</subject><subject>tissue micro array</subject><issn>0270-4137</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><recordid>eNp90MlOAzEMANAIgURZLnxBJC4IacBZZiY9IsQmKoEKnEeZxFMFlWRIpiw3PoFv5EtIKScOXOyDn-PYhOwxOGIA_LiPIR1xCUKtkRGDcV0AyHKdjIDXUEgm6k2yldIjQObAR-R5inZh0NLryTWn-NZHTMkFT12imqYhBj-j2lvqvMUec_ADzcg6M4RIQ0f7kHOeO_Mh5Sbn6dn04uvj0-NMD-4Fl7U06AGp0d5g3CEbnZ4n3P3N2-Th_Oz-9LKY3FxcnZ5MCiNqUAV2wrJKVaiM1FyPeYs4VlrJUrWttao2XJqS6brjFcPScimNgKrFVkArmRXb5GD1bp7_vMA0NE8uGZzPtcewSA2XHCrBmCoz3f9DH8Mi-vy7rIQUVSkZZHW4UiYvlCJ2TR_dk47vDYNmef1muWnzc_2M2Qq_ujm-_yOb2-nN3arnG9cviTI</recordid><startdate>20200901</startdate><enddate>20200901</enddate><creator>Bonk, Sarah</creator><creator>Kluth, Martina</creator><creator>Jansen, Kristina</creator><creator>Hube‐Magg, Claudia</creator><creator>Makrypidi‐Fraune, Georgia</creator><creator>Höflmayer, Doris</creator><creator>Weidemann, Sören</creator><creator>Möller, Katharina</creator><creator>Uhlig, Ria</creator><creator>Büscheck, Franziska</creator><creator>Luebke, Andreas M.</creator><creator>Burandt, Eike</creator><creator>Clauditz, Till S.</creator><creator>Steurer, Stefan</creator><creator>Schlomm, Thorsten</creator><creator>Huland, Hartwig</creator><creator>Heinzer, Hans</creator><creator>Sauter, Guido</creator><creator>Simon, Ronald</creator><creator>Dum, David</creator><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0158-4258</orcidid></search><sort><creationdate>20200901</creationdate><title>Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer</title><author>Bonk, Sarah ; Kluth, Martina ; Jansen, Kristina ; Hube‐Magg, Claudia ; Makrypidi‐Fraune, Georgia ; Höflmayer, Doris ; Weidemann, Sören ; Möller, Katharina ; Uhlig, Ria ; Büscheck, Franziska ; Luebke, Andreas M. ; Burandt, Eike ; Clauditz, Till S. ; Steurer, Stefan ; Schlomm, Thorsten ; Huland, Hartwig ; Heinzer, Hans ; Sauter, Guido ; Simon, Ronald ; Dum, David</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3708-ef3d1686e8c4a2a92bee98a8458bbdd87c24c51a7f261e5d244c306beb30b41d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biopsy</topic><topic>Cell proliferation</topic><topic>Epithelium</topic><topic>Immunohistochemistry</topic><topic>Kallikrein</topic><topic>Lymph nodes</topic><topic>Metastases</topic><topic>Peptidase</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>PSA</topic><topic>Serine</topic><topic>Serum levels</topic><topic>tissue micro array</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bonk, Sarah</creatorcontrib><creatorcontrib>Kluth, Martina</creatorcontrib><creatorcontrib>Jansen, Kristina</creatorcontrib><creatorcontrib>Hube‐Magg, Claudia</creatorcontrib><creatorcontrib>Makrypidi‐Fraune, Georgia</creatorcontrib><creatorcontrib>Höflmayer, Doris</creatorcontrib><creatorcontrib>Weidemann, Sören</creatorcontrib><creatorcontrib>Möller, Katharina</creatorcontrib><creatorcontrib>Uhlig, Ria</creatorcontrib><creatorcontrib>Büscheck, Franziska</creatorcontrib><creatorcontrib>Luebke, Andreas M.</creatorcontrib><creatorcontrib>Burandt, Eike</creatorcontrib><creatorcontrib>Clauditz, Till S.</creatorcontrib><creatorcontrib>Steurer, Stefan</creatorcontrib><creatorcontrib>Schlomm, Thorsten</creatorcontrib><creatorcontrib>Huland, Hartwig</creatorcontrib><creatorcontrib>Heinzer, Hans</creatorcontrib><creatorcontrib>Sauter, Guido</creatorcontrib><creatorcontrib>Simon, Ronald</creatorcontrib><creatorcontrib>Dum, David</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bonk, Sarah</au><au>Kluth, Martina</au><au>Jansen, Kristina</au><au>Hube‐Magg, Claudia</au><au>Makrypidi‐Fraune, Georgia</au><au>Höflmayer, Doris</au><au>Weidemann, Sören</au><au>Möller, Katharina</au><au>Uhlig, Ria</au><au>Büscheck, Franziska</au><au>Luebke, Andreas M.</au><au>Burandt, Eike</au><au>Clauditz, Till S.</au><au>Steurer, Stefan</au><au>Schlomm, Thorsten</au><au>Huland, Hartwig</au><au>Heinzer, Hans</au><au>Sauter, Guido</au><au>Simon, Ronald</au><au>Dum, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer</atitle><jtitle>The Prostate</jtitle><date>2020-09-01</date><risdate>2020</risdate><volume>80</volume><issue>13</issue><spage>1097</spage><epage>1107</epage><pages>1097-1107</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><abstract>Background
Kallikrein‐related peptidase 2 (KLK2)—like KLK3 (prostate‐specific antigen [PSA])—belongs to the highly conserved serine proteases of the glandular kallikrein protein family (KLK family). Studies suggested that measurement of KLK2 serum levels advanced the predictive accuracy of PSA testing in prostate cancer.
Methods
To clarify the potential utility of KLK2 as a prognostic tissue biomarker, KLK2 expression was analyzed by immunohistochemistry in more than 12 000 prostate cancers.
Results
Normal epithelium cells usually showed weak to moderate KLK2 immunostaining, whereas KLK2 was negative in 23%, weak in 38%, moderate in 35%, and strong in 4% of 9576 analyzable cancers. Lost or reduced KLK2 immunostaining was associated with advanced tumor stage, high Gleason score, lymph node metastasis, increased cell proliferation, positive resection margin, and early PSA recurrence (P < .0001). Comparison with previously analyzed molecular alterations revealed a strong association of KLK2 loss and presence of TMPRSS2:ERG fusion (P < .0001), most of all analyzed common deletions (9 of 11; P ≤ .03), and decreased PSA immunostaining (P < .0001 each). Cancers with combined negative or weak immunostaining of KLK2 and PSA showed worse prognosis than cancers with at least moderate staining of one or both proteins (P < .0001). Multivariate analyses including established preoperative and postoperative prognostic parameters showed a strong independent prognostic impact of KLK2 loss alone or in combination of PSA, especially in erythroblast transformation‐specific‐negative cancers (P ≤ .006).
Conclusions
Loss of KLK2 expression is a potentially useful prognostic marker in prostate cancer. Analysis of KLK2 alone or in combination with PSA may be useful for estimating cancer aggressiveness at the time of biopsy.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/pros.24038</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-0158-4258</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | The Prostate, 2020-09, Vol.80 (13), p.1097-1107 |
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| language | eng |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Biopsy Cell proliferation Epithelium Immunohistochemistry Kallikrein Lymph nodes Metastases Peptidase Prognosis Prostate cancer PSA Serine Serum levels tissue micro array |
| title | Reduced KLK2 expression is a strong and independent predictor of poor prognosis in ERG‐negative prostate cancer |
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