Detection of the TNFSF members BAFF, APRIL, TWEAK and their receptors in normal kidney and renal cell carcinomas

Anal Cell Pathol (Amst). 2011;34(1-2):49-60. doi: 10.3233/ACP-2011-0001.

Abstract

In advanced renal cell carcinoma (RCC), surgery combined with systemic chemotherapy and immunotherapy have had limited effectiveness. Therapeutic modalities targeting VEGF, PDGF, and c-kit using tyrosine kinase inhibitors and m-TOR using specific biologic factors are in development. Therapeutic approaches targeting TNF-alpha have shown limited efficacy, while anti-TRAIL (TNFSF10) antibodies have shown enhanced activity. The presence and potential significance of other members of the TNFSF has not been investigated. Here, we assayed the TNFSF members APRIL, BAFF, TWEAK and their receptors (BCMA, TACI, BAFFR, Fn14) in 86 conventional type clear cell RCC, using immunohistochemistry and correlated our findings with histological data and, in a limited series, follow-up of patients. We observed a differential expression of these TNFSF ligands and receptors in cancerous and non-cancerous structures. BAFF was found in all RCC; APRIL expression is associated with an aggressive phenotype, correlating negatively with patients' disease-free survival, while TWEAK and its receptor Fn14 are heterogeneously expressed, correlating negatively with the grade and survival of RCC patients. This is the first study, presenting together the TNFSF members APRIL, BAFF, TWEAK and their receptors in different areas of normal renal tissue and RCC, suggesting a potential role of these TNFSF members in renal tumor biology.

MeSH terms

  • B-Cell Activating Factor / genetics
  • B-Cell Activating Factor / metabolism*
  • B-Cell Activation Factor Receptor / genetics
  • B-Cell Activation Factor Receptor / metabolism*
  • B-Cell Maturation Antigen / genetics
  • B-Cell Maturation Antigen / metabolism*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cytokine TWEAK
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology
  • Ligands
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • TWEAK Receptor
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 13 / metabolism*
  • Tumor Necrosis Factors / genetics
  • Tumor Necrosis Factors / metabolism*

Substances

  • B-Cell Activating Factor
  • B-Cell Activation Factor Receptor
  • B-Cell Maturation Antigen
  • Cytokine TWEAK
  • Ligands
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • TNFRSF12A protein, human
  • TNFRSF13C protein, human
  • TNFRSF17 protein, human
  • TNFSF12 protein, human
  • TNFSF13 protein, human
  • TNFSF13B protein, human
  • TWEAK Receptor
  • Tumor Necrosis Factor Ligand Superfamily Member 13
  • Tumor Necrosis Factors