title: Tumoral cubilin is a predictive marker for treatment of renal cancer patients with sunitinib and sorafenib.
abstract: OBJECTIVE
  Tyrosine kinase inhibitors like sunitinib and sorafenib are commonly used to treat metastatic renal cell cancer patients. Cubilin is a membrane protein expressed in the proximal renal tubule. Cubilin and megalin function together as endocytic receptors mediating uptake of many proteins. There is no established predictive marker for metastatic renal cell cancer patients and the purpose of the present study was to assess if cubilin can predict response to treatment with tyrosine kinase inhibitors.
  
  
  METHODS
  Cubilin protein expression was analyzsed in tumor tissue from a cohort of patients with metastatic renal cell cancer (n = 139) using immunohistochemistry. One hundred and thirty six of the patients were treated with sunitinib or sorafenib in the first- or second-line setting. Thirty of these were censored because of toxicity leading to the termination of treatment and the remaining (n = 106) were selected for the current study.
  
  
  RESULTS
  Fifty-three (50%) of the tumors expressed cubilin in the membrane. The median progression-free survival was 8 months in patients with cubilin expressing tumors and 4 months in the cubilin negative group. In addition, the overall survival was better for patients with cubilin positive tumors. We also found that the fraction of cubilin negative patients was significantly higher in the non-responding group (PFS ≤3 months) compared to responding patients (PFS >3 months).
  
  
  CONCLUSIONS
  We show for the first time that tumoral expression of cubilin is a positive predictive marker for treatment of metastatic renal cell cancer patients with sunitinib and sorafenib.
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.|Department of Oncology, Uppsala University Hospital, Entrance 78, 751 85, Uppsala, Sweden.
authors.forename: Marjut
authors.initials: M
authors.lastname: Niinivirta
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.|Department of Oncology, Uppsala University Hospital, Entrance 78, 751 85, Uppsala, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.affiliation: Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Edqvist
authors.affiliation: Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Pontén
authors.affiliation: Department of Immunology, Genetics and Pathology and Science for Life Laboratory, Uppsala University, Dag Hammarskjölds väg 20, 751 85, Uppsala, Sweden.|Department of Surgical Pathology, Uppsala University Hospital, 75185, Uppsala, Sweden.
authors.forename: Anca
authors.initials: A
authors.lastname: Dragomir
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Gustav.Ullenhag@igp.uu.se.|Department of Oncology, Uppsala University Hospital, Entrance 78, 751 85, Uppsala, Sweden. Gustav.Ullenhag@igp.uu.se.
authors.forename: Gustav J
authors.initials: GJ
authors.lastname: Ullenhag
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D011379:Prognosis; D011758:Pyrroles / Q000627:therapeutic use*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000077157:Sorafenib; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D054316:Biomarkers, Pharmacological; D014408:Biomarkers, Tumor; D007211:Indoles; D010671:Phenylurea Compounds; D011758:Pyrroles; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor; D009536:Niacinamide; D000077157:Sorafenib; D000077210:Sunitinib
keywords: Cubilin; Predictive marker; Renal cancer; Tissue microarray; Tyrosine kinase inhibitor