PittsburghV1, France, Analysis, bibRecord, 000337

BAP1 Immunohistochemistry Predicts Outcomes in a Multi-Institutional Cohort with Clear Cell Renal Cell Carcinoma

Identifieur interne : 000337 ( France/Analysis ); précédent : 000336; suivant : 000338

BAP1 Immunohistochemistry Predicts Outcomes in a Multi-Institutional Cohort with Clear Cell Renal Cell Carcinoma

Auteurs : Payal Kapur [États-Unis] ; Alana Christie ; Jay D. Raman [États-Unis] ; Matthew T. Then [États-Unis] ; Philipp Nuhn [Allemagne] ; Alexander Buchner [Allemagne] ; Patrick Bastian [Allemagne] ; Christian Seitz [Italie, Autriche] ; Shahrokh F. Shariat [Autriche] ; Karim Bensalah [France] ; Nathalie Rioux-Leclercq [France] ; Xian-Jin Xie [États-Unis] ; Yair Lotan [États-Unis] ; Vitaly Margulis [États-Unis] ; James Brugarolas [États-Unis]

Source :

The Journal of urology [ 0022-5347 ] ; 2014.

RBID : Pascal:14-0111569

Descripteurs français

Pascal (Inist)
- Cancer rein, Gène suppresseur tumeur, Immunohistochimie, Facteur prédictif, Pronostic, Etude cohorte, Carcinome cellule claire, Mésonéphrome, Hypernéphrome, Rein, Protéine, Homme, Facteur risque, Néphrologie, Urologie, Gène BAP1.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Clear cell carcinoma, Cohort study, Grawitz tumor, Human, Immunohistochemistry, Kidney, Kidney cancer, Mesonephroma, Nephrology, Predictive factor, Prognosis, Protein, Risk factor, Tumor suppressor gene, Urology.

Abstract

Purpose: Mutations in the tumor suppressor gene BAP1 occur in approximately 15% of clear cell renal cell carcinoma cases. Sequencing efforts demonstrated worse outcomes in patients with BAP1 mutated clear cell renal cell carcinoma. We investigated the clinicopathological significance and oncologic outcomes of BAP1 loss using a previously validated immunohistochemical assay. Materials and Methods: Immunohistochemistry for BAP1 was performed on tissue microarray sections from 559 nonmetastatic clear cell renal cell carcinoma cases treated with nephrectomy at multiple institutions. The association of BAP1 expression with clinicopathological parameters was analyzed using the Wilcoxon rank sum and Cochran-Mantel-Haenszel tests. Survival was assessed by Cox regression analysis, which also identified independent predictors of time dependent outcomes. Results: At a median followup of 50 months (range 0 to 183) 86 of 483 patients (17.8%) experienced recurrence and 121 of 559 (21.6%) had died. BAP1 was negative in 82 of 559 tumors (14.7%). BAP1 loss was associated with adverse clinicopathological variables, including high Fuhrman grade (p <0.0001), advanced pT stage (p = 0.0021), sarcomatoid dedifferentiation (p = 0.0001) and necrosis (p <0.0001). Cox regression revealed that patients with BAP1 negative tumors had significantly worse disease-free survival (HR 2.9, 95% CI 1.8-47, p <0.0001) and overall survival (HR 2.0, 95% CI 1.3-3.1, p = 0.0010) than patients with BAP1 positive tumors. Conclusions: Immunohistochemistry for BAP1 serves as a powerful marker to predict poor oncologic outcomes and adverse clinicopathological features in patients with nonmetastatic clear cell renal cell carcinoma. BAP1 assessment using immunohistochemistry on needle biopsy may benefit preoperative risk stratification and guide treatment planning in the future.

Affiliations:

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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">BAP1 Immunohistochemistry Predicts Outcomes in a Multi-Institutional Cohort with Clear Cell Renal Cell Carcinoma</title>
<author><name sortKey="Kapur, Payal" sort="Kapur, Payal" uniqKey="Kapur P" first="Payal" last="Kapur">Payal Kapur</name>
<affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Department of Pathology, University of Texas Southwestern Medical Center</s1>
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<author><name sortKey="Seitz, Christian" sort="Seitz, Christian" uniqKey="Seitz C" first="Christian" last="Seitz">Christian Seitz</name>
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<wicri:noRegion>Central Hospital of Bolzano</wicri:noRegion>
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<author><name sortKey="Bensalah, Karim" sort="Bensalah, Karim" uniqKey="Bensalah K" first="Karim" last="Bensalah">Karim Bensalah</name>
<affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Department of Urology and Pathology, University of Rennes</s1>
<s2>Rennes</s2>
<s3>FRA</s3>
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<country>France</country>
<placeName><region type="region">Région Bretagne</region>
<region type="old region">Région Bretagne</region>
<settlement type="city">Rennes</settlement>
</placeName>
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<affiliation wicri:level="3"><inist:fA14 i1="12"><s1>Department of Urology and Pathology, University of Rennes</s1>
<s2>Rennes</s2>
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<sZ>11 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Région Bretagne</region>
<region type="old region">Région Bretagne</region>
<settlement type="city">Rennes</settlement>
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<author><name sortKey="Xie, Xian Jin" sort="Xie, Xian Jin" uniqKey="Xie X" first="Xian-Jin" last="Xie">Xian-Jin Xie</name>
<affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Simmons Cancer Center, University of Texas Southwestern Medical Center</s1>
<s2>Dallas, Texas</s2>
<s3>USA</s3>
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</inist:fA14>
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<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lotan, Yair" sort="Lotan, Yair" uniqKey="Lotan Y" first="Yair" last="Lotan">Yair Lotan</name>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Urology, University of Texas Southwestern Medical Center</s1>
<s2>Dallas, Texas</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Margulis, Vitaly" sort="Margulis, Vitaly" uniqKey="Margulis V" first="Vitaly" last="Margulis">Vitaly Margulis</name>
<affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Department of Urology, University of Texas Southwestern Medical Center</s1>
<s2>Dallas, Texas</s2>
<s3>USA</s3>
<sZ>1 aut.</sZ>
<sZ>13 aut.</sZ>
<sZ>14 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Brugarolas, James" sort="Brugarolas, James" uniqKey="Brugarolas J" first="James" last="Brugarolas">James Brugarolas</name>
<affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Department of Internal Medicine, University of Texas Southwestern Medical Center</s1>
<s2>Dallas, Texas</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="04"><s1>Department of Developmental Biology, University of Texas Southwestern Medical Center</s1>
<s2>Dallas, Texas</s2>
<s3>USA</s3>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Simmons Cancer Center, University of Texas Southwestern Medical Center</s1>
<s2>Dallas, Texas</s2>
<s3>USA</s3>
<sZ>12 aut.</sZ>
<sZ>15 aut.</sZ>
</inist:fA14>
<country>États-Unis</country>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">The Journal of urology</title>
<title level="j" type="abbreviated">J. urol.</title>
<idno type="ISSN">0022-5347</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">The Journal of urology</title>
<title level="j" type="abbreviated">J. urol.</title>
<idno type="ISSN">0022-5347</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Clear cell carcinoma</term>
<term>Cohort study</term>
<term>Grawitz tumor</term>
<term>Human</term>
<term>Immunohistochemistry</term>
<term>Kidney</term>
<term>Kidney cancer</term>
<term>Mesonephroma</term>
<term>Nephrology</term>
<term>Predictive factor</term>
<term>Prognosis</term>
<term>Protein</term>
<term>Risk factor</term>
<term>Tumor suppressor gene</term>
<term>Urology</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Cancer rein</term>
<term>Gène suppresseur tumeur</term>
<term>Immunohistochimie</term>
<term>Facteur prédictif</term>
<term>Pronostic</term>
<term>Etude cohorte</term>
<term>Carcinome cellule claire</term>
<term>Mésonéphrome</term>
<term>Hypernéphrome</term>
<term>Rein</term>
<term>Protéine</term>
<term>Homme</term>
<term>Facteur risque</term>
<term>Néphrologie</term>
<term>Urologie</term>
<term>Gène BAP1</term>
</keywords>
<keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Purpose: Mutations in the tumor suppressor gene BAP1 occur in approximately 15% of clear cell renal cell carcinoma cases. Sequencing efforts demonstrated worse outcomes in patients with BAP1 mutated clear cell renal cell carcinoma. We investigated the clinicopathological significance and oncologic outcomes of BAP1 loss using a previously validated immunohistochemical assay. Materials and Methods: Immunohistochemistry for BAP1 was performed on tissue microarray sections from 559 nonmetastatic clear cell renal cell carcinoma cases treated with nephrectomy at multiple institutions. The association of BAP1 expression with clinicopathological parameters was analyzed using the Wilcoxon rank sum and Cochran-Mantel-Haenszel tests. Survival was assessed by Cox regression analysis, which also identified independent predictors of time dependent outcomes. Results: At a median followup of 50 months (range 0 to 183) 86 of 483 patients (17.8%) experienced recurrence and 121 of 559 (21.6%) had died. BAP1 was negative in 82 of 559 tumors (14.7%). BAP1 loss was associated with adverse clinicopathological variables, including high Fuhrman grade (p <0.0001), advanced pT stage (p = 0.0021), sarcomatoid dedifferentiation (p = 0.0001) and necrosis (p <0.0001). Cox regression revealed that patients with BAP1 negative tumors had significantly worse disease-free survival (HR 2.9, 95% CI 1.8-47, p <0.0001) and overall survival (HR 2.0, 95% CI 1.3-3.1, p = 0.0010) than patients with BAP1 positive tumors. Conclusions: Immunohistochemistry for BAP1 serves as a powerful marker to predict poor oncologic outcomes and adverse clinicopathological features in patients with nonmetastatic clear cell renal cell carcinoma. BAP1 assessment using immunohistochemistry on needle biopsy may benefit preoperative risk stratification and guide treatment planning in the future.</div>
</front>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Autriche</li>
<li>France</li>
<li>Italie</li>
<li>États-Unis</li>
</country>
<region><li>Bavière</li>
<li>District de Düsseldorf</li>
<li>District de Haute-Bavière</li>
<li>Pennsylvanie</li>
<li>Rhénanie-du-Nord-Westphalie</li>
<li>Région Bretagne</li>
<li>Texas</li>
<li>Vienne (Autriche)</li>
</region>
<settlement><li>Düsseldorf</li>
<li>Munich</li>
<li>Rennes</li>
<li>Vienne (Autriche)</li>
</settlement>
<orgName><li>Université Louis-et-Maximilien de Munich</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Christie, Alana" sort="Christie, Alana" uniqKey="Christie A" first="Alana" last="Christie">Alana Christie</name>
</noCountry>
<country name="États-Unis"><region name="Texas"><name sortKey="Kapur, Payal" sort="Kapur, Payal" uniqKey="Kapur P" first="Payal" last="Kapur">Payal Kapur</name>
</region>
<name sortKey="Brugarolas, James" sort="Brugarolas, James" uniqKey="Brugarolas J" first="James" last="Brugarolas">James Brugarolas</name>
<name sortKey="Brugarolas, James" sort="Brugarolas, James" uniqKey="Brugarolas J" first="James" last="Brugarolas">James Brugarolas</name>
<name sortKey="Brugarolas, James" sort="Brugarolas, James" uniqKey="Brugarolas J" first="James" last="Brugarolas">James Brugarolas</name>
<name sortKey="Kapur, Payal" sort="Kapur, Payal" uniqKey="Kapur P" first="Payal" last="Kapur">Payal Kapur</name>
<name sortKey="Lotan, Yair" sort="Lotan, Yair" uniqKey="Lotan Y" first="Yair" last="Lotan">Yair Lotan</name>
<name sortKey="Margulis, Vitaly" sort="Margulis, Vitaly" uniqKey="Margulis V" first="Vitaly" last="Margulis">Vitaly Margulis</name>
<name sortKey="Raman, Jay D" sort="Raman, Jay D" uniqKey="Raman J" first="Jay D." last="Raman">Jay D. Raman</name>
<name sortKey="Then, Matthew T" sort="Then, Matthew T" uniqKey="Then M" first="Matthew T." last="Then">Matthew T. Then</name>
<name sortKey="Xie, Xian Jin" sort="Xie, Xian Jin" uniqKey="Xie X" first="Xian-Jin" last="Xie">Xian-Jin Xie</name>
</country>
<country name="Allemagne"><region name="Bavière"><name sortKey="Nuhn, Philipp" sort="Nuhn, Philipp" uniqKey="Nuhn P" first="Philipp" last="Nuhn">Philipp Nuhn</name>
</region>
<name sortKey="Bastian, Patrick" sort="Bastian, Patrick" uniqKey="Bastian P" first="Patrick" last="Bastian">Patrick Bastian</name>
<name sortKey="Buchner, Alexander" sort="Buchner, Alexander" uniqKey="Buchner A" first="Alexander" last="Buchner">Alexander Buchner</name>
</country>
<country name="Italie"><noRegion><name sortKey="Seitz, Christian" sort="Seitz, Christian" uniqKey="Seitz C" first="Christian" last="Seitz">Christian Seitz</name>
</noRegion>
</country>
<country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Seitz, Christian" sort="Seitz, Christian" uniqKey="Seitz C" first="Christian" last="Seitz">Christian Seitz</name>
</region>
<name sortKey="Shariat, Shahrokh F" sort="Shariat, Shahrokh F" uniqKey="Shariat S" first="Shahrokh F." last="Shariat">Shahrokh F. Shariat</name>
</country>
<country name="France"><region name="Région Bretagne"><name sortKey="Bensalah, Karim" sort="Bensalah, Karim" uniqKey="Bensalah K" first="Karim" last="Bensalah">Karim Bensalah</name>
</region>
<name sortKey="Rioux Leclercq, Nathalie" sort="Rioux Leclercq, Nathalie" uniqKey="Rioux Leclercq N" first="Nathalie" last="Rioux-Leclercq">Nathalie Rioux-Leclercq</name>
</country>
</tree>
</affiliations>
</record>

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BAP1 Immunohistochemistry Predicts Outcomes in a Multi-Institutional Cohort with Clear Cell Renal Cell Carcinoma

BAP1 Immunohistochemistry Predicts Outcomes in a Multi-Institutional Cohort with Clear Cell Renal Cell Carcinoma

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