title: Clinical, molecular, and genetic correlates of lymphatic spread in clear cell renal cell carcinoma.
abstract: BACKGROUND
  While it is well known that clear cell renal cell carcinoma (ccRCC) that presents with lymphatic spread is associated with an extremely poor prognosis, its molecular and genetic biology is poorly understood.
  
  
  OBJECTIVE
  Define the clinicopathologic, molecular, and genetic biological characteristics of these tumors in comparison to nonmetastatic (N0M0) renal cell carcinomas.
  
  
  METHODS
  A retrospective study defined clinicopathologic features, expression of 28 molecular markers, and occurrence of chromosomal aberrations for their correlation with lymphatic spread in three cohorts of 502, 196, and 272 patients, respectively.
  
  
  METHODS
  Fisher exact test or the χ(2) test were used to compare categorical variables; continuous variables were compared with the Mann-Whitney U test or student t test. Cut-off values were calculated based on receiver operating characteristic curves and the Youden Index. Uni- and multivariate regression analyses were used to investigate the correlation with lymphatic spread.
  
  
  CONCLUSIONS
  In clinical analyses, a predictive model consisting of smoking history (p=0.040), T stage (p<0.0001), Fuhrman grade (p<0.0001), Eastern Cooperative Oncology Group performance status (p<0.0001), and microvascular invasion (p<0.0001) was independently associated with lymphatic spread. After adjustment with these clinical variables, low carbonic anhydrase IX (CAIX) (p=0.043) and high epithelial vascular endothelial growth factor receptor 2 (p=0.033) protein expression were associated with a higher risk of lymphatic spread, and loss of chromosome 3p (p<0.0001) with a lower risk. The current study is limited by its retrospective design, small sample size, and single-center experience.
  
  
  CONCLUSIONS
  The low rates of CAIX expression and loss of chromosome 3p suggest that lymphatic spread in ccRCC occurs independently of von Hippel-Lindau tumor suppressor inactivation.
authors.affiliation: Institute of Urologic Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Nils
authors.initials: N
authors.lastname: Kroeger
authors.forename: David B
authors.initials: DB
authors.lastname: Seligson
authors.forename: Tobias
authors.initials: T
authors.lastname: Klatte
authors.forename: Edward N
authors.initials: EN
authors.lastname: Rampersaud
authors.forename: Frédéric D
authors.initials: FD
authors.lastname: Birkhäuser
authors.forename: P Nagesh
authors.initials: PN
authors.lastname: Rao
authors.forename: John T
authors.initials: JT
authors.lastname: Leppert
authors.forename: Nazy
authors.initials: N
authors.lastname: Zomorodian
authors.forename: Fairooz F
authors.initials: FF
authors.lastname: Kabbinavar
authors.forename: Arie S
authors.initials: AS
authors.lastname: Belldegrun
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Pantuck
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000096:biosynthesis; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D002869:Chromosome Aberrations; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D040301:Vascular Endothelial Growth Factor Receptor-2; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases