title: Loss of BAP1 protein expression in the first metastatic site predicts prognosis in patients with clear cell renal cell carcinoma.
abstract: To investigate the intratumoral heterogeneity of BAP1 and PBRM1 expression at the primary site and metastatic sites and to evaluate whether BAP1 and PBRM1 expression in metastatic sites of clear cell renal cell carcinoma (ccRCC) has prognostic value.
  
  
  
  We collected paired samples from the primary site and the first metastatic site in 41 patients with ccRCC. Immunohistochemistry analyses were performed for the expression of BAP1 and PBRM1 proteins. We retrospectively analyzed the associations between the expression of BAP1 and PBRM1 and overall survival (OS).
  
  
  
  The most common first metastatic sites were lung (68.3%) and lymph node (12.2%). BAP1 protein expression was negative in 8 (19.5%) primary sites and in 11 (26.8%) metastatic sites. PBRM1 protein expression was negative in 9 (22.0%) primary sites and in 11 (26.8%) metastatic sites. The incidences of intratumoral heterogeneity for BAP1 and PBRM1 protein expression in primary/metastatic sites were 9.8%/2.4% and 24.4%/7.3%, respectively. The concordance rates between primary and metastatic sites for BAP1 and PBRM1 protein expression were 82.9% and 63.4%, respectively. Median OS from the first occurrence of metastasis in patients with BAP1-positive and BAP1-negative metastatic sites were 97 months (95% CI: 58-136) and 51 months (95% CI: 13-82), respectively (P = 0.0077). Median OS in patients with PBRM1-positive and PBRM1-negative metastatic sites were 82 (95% CI: 42-97) and 120 (95% CI: 52-120) months, respectively (P = 0.25).
  
  
  
  Intratumoral heterogeneity of BAP1 protein expression is more frequent in primary tumor than in metastatic sites. The loss of BAP1 protein expression in metastatic sites predicts poor prognosis in patients with ccRCC.
authors.affiliation: Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan. Electronic address: yujmiura@mac.com.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miura
authors.affiliation: Department of Pathology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Inoshita
authors.affiliation: Department of Urology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Department of Pathology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Miyama
authors.affiliation: Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Oki
authors.affiliation: Department of Urology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Suguru
authors.initials: S
authors.lastname: Oka
authors.affiliation: Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kondoh
authors.affiliation: Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Ozaki
authors.affiliation: Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanabe
authors.affiliation: Department of Urology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kurosawa
authors.affiliation: Department of Urology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Urakami
authors.affiliation: Department of Thoracic Surgery, Toranomon Hospital, Tokyo, Japan.
authors.forename: Tadasu
authors.initials: T
authors.lastname: Kohno
authors.affiliation: Department of Urology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Okaneya
authors.affiliation: Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Takano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*
chemical_list: C400134:BAP1 protein, human; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
keywords: BAP1; Immunohistochemistry; Intratumoral heterogeneity; PBRM1