title: Cytoplasmic PAR-3 protein expression is associated with adverse prognostic factors in clear cell renal cell carcinoma and independently impacts survival.
abstract: Clear cell renal cell carcinomas (ccRCCs) represent 70% of renal cancers, and several clinical and histolopathological factors are implicated in their prognosis. We recently demonstrated that the overexpression of PAR-3 protein encoded by the PARD3 gene could be implicated in renal oncogenesis. The object of this work was to study the association of intratumoral PAR-3 expression with known prognostic parameters and clinical outcome. In this aim, PAR-3 expression was assessed by immunohistochemistry in ccRCC tumors of 101 patients from 2003 to 2005. The immunostaining of PAR-3 was scored either as membranous (mPAR-3) or as both membranous and cytoplasmic (cPAR-3). Cytoplasmic PAR-3 was significantly associated with worse histopathological and clinical prognostic factors: Fuhrman grades 3 and 4, tumor necrosis, sarcomatoid component, adrenal invasion, renal and hilar fat invasion, eosinophilic component, a noninactivated VHL gene, higher tumor grade, lymph node involvement, metastasis, and worse clinical Eastern Cooperative Oncology Group and S classification scores. After multivariate analysis, 2 parameters were independently associated with cPAR-3: necrosis and eosinophilic components. In addition, cPAR-3 patients had shorter overall and progression-free survivals independently from strong prognostic validated factors like metastases. A cytoplasmic expression of PAR-3 is therefore implicated in worse clinical and pathological cancer features in ccRCC and could be useful to identify patients with high-risk tumors.
authors.affiliation: Service d'Anatomie et Cytologie Pathologiques, CHU de Rennes, 35000 Rennes, France; Service de Cytogénétique et Biologie Cellulaire, CHU de Rennes, 35000 Rennes, France; UMR 6290 IGDR, Cancer du Rein-BIOSIT, Faculté de Médecine de Rennes, 35000 Rennes, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Dagher
authors.affiliation: Service de Cytogénétique et Biologie Cellulaire, CHU de Rennes, 35000 Rennes, France; UMR 6290 IGDR, Cancer du Rein-BIOSIT, Faculté de Médecine de Rennes, 35000 Rennes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dugay
authors.affiliation: Service d'Anatomie et Cytologie Pathologiques, CHU de Rennes, 35000 Rennes, France; UMR 6290 IGDR, Cancer du Rein-BIOSIT, Faculté de Médecine de Rennes, 35000 Rennes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.affiliation: UMR 6290 IGDR, Cancer du Rein-BIOSIT, Faculté de Médecine de Rennes, 35000 Rennes, France; Service d'Urologie, CHU de Rennes, 35000 Rennes, France.
authors.forename: Gregory
authors.initials: G
authors.lastname: Verhoest
authors.affiliation: Service de Pharmacologie Clinique, CHU de Rennes, 35000 Rennes, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Oger
authors.affiliation: Service d'Urologie, CHU de Rennes, 35000 Rennes, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.affiliation: Service de Cytogénétique et Biologie Cellulaire, CHU de Rennes, 35000 Rennes, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Cabillic
authors.affiliation: UMR 6290 IGDR, Cancer du Rein-BIOSIT, Faculté de Médecine de Rennes, 35000 Rennes, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Jouan
authors.affiliation: Service d'Anatomie et Cytologie Pathologiques, CHU de Rennes, 35000 Rennes, France; UMR 6290 IGDR, Cancer du Rein-BIOSIT, Faculté de Médecine de Rennes, 35000 Rennes, France.
authors.forename: Solene-Florence
authors.initials: SF
authors.lastname: Kammerer-Jacquet
authors.affiliation: Service de Génétique, CHU de Bordeaux, 33076 Bordeaux, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Fergelot
authors.affiliation: UMR 6290 IGDR, Cancer du Rein-BIOSIT, Faculté de Médecine de Rennes, 35000 Rennes, France; Service de Néphrologie, CHU de Rennes, 35000 Rennes, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Vigneau
authors.affiliation: UMR 6290 IGDR, Cancer du Rein-BIOSIT, Faculté de Médecine de Rennes, 35000 Rennes, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Arlot-Bonnemains
authors.affiliation: Service de Cytogénétique et Biologie Cellulaire, CHU de Rennes, 35000 Rennes, France; UMR 6290 IGDR, Cancer du Rein-BIOSIT, Faculté de Médecine de Rennes, 35000 Rennes, France. Electronic address: marc-antoine.belaud-rotureau@univ-rennes1.fr.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Belaud-Rotureau
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C509689:PARD3 protein, human
keywords: Biomarker; PAR-3 protein; Prognosis; Renal cell carcinoma; Survival