A Study of Angiogenesis Markers in Patients with Renal Cell Carcinoma Undergoing Therapy with Sunitinib

Anticancer Res. 2017 Jan;37(1):253-259. doi: 10.21873/anticanres.11315.

Abstract

Background: Sunitinib is a tyrosine kinase inhibitor (TKI) targeting tumour angiogenesis in patients with advanced renal cell carcinoma (RCC). Currently no universally agreed model exists correlating the expression of angiogenesis markers with the success of treatment.

Patients and methods: We retrospectively analysed archival tissue for 59 RCC patients treated with sunitinib. The expression of angiogenesis markers VEGF-A, VEGFR, PDGFββ, PDGFR, CCND1 and CA9 was assessed by immunohistochemistry (IHC) and correlated with overall survival (OS) and progression-free survival (PFS).

Results: The median OS and median PFS of the whole group of patients was 24.6 months (17.3-34.2) and 19.5 months (11-27) respectively. VEGFA was positive in 29% of tumors, whereas VEGFR was expressed in only 12% of tumours. PDGFββ and its receptor were detected in a minority of cases. CCND1 and CA9 were positive in 44% and 60% of cases.

Conclusion: The OS and PFS achieved by our patients reflected previous observations seen with sunitinib, but no correlation was found between expression of angiogenesis markers and clinical outcome.

Keywords: CA9; CCND1; PDGFR; PDGFββ; Renal cell carcinoma; VEGF-A; VEGFR; angiogenesis; outcome; sunitinib; survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angiogenesis Inhibitors / pharmacology*
  • Angiogenesis Inhibitors / therapeutic use
  • Antigens, Neoplasm / metabolism
  • Becaplermin
  • Biomarkers, Tumor / metabolism*
  • Carbonic Anhydrase IX / metabolism
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cyclin D1 / metabolism
  • Disease-Free Survival
  • Female
  • Humans
  • Indoles / pharmacology*
  • Indoles / therapeutic use
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Proto-Oncogene Proteins c-sis / metabolism
  • Pyrroles / pharmacology*
  • Pyrroles / therapeutic use
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Sunitinib
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CCND1 protein, human
  • Indoles
  • Proto-Oncogene Proteins c-sis
  • Pyrroles
  • Vascular Endothelial Growth Factor A
  • Cyclin D1
  • Becaplermin
  • Receptors, Platelet-Derived Growth Factor
  • Receptors, Vascular Endothelial Growth Factor
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Sunitinib