Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma

Cancer. 2010 Nov 15;116(22):5219-25. doi: 10.1002/cncr.25512.


Background: Adult "translocation" renal cell carcinoma (RCC), bearing transcription factor E3 (TFE3) gene fusions at Xp11.2, is a recently recognized, unique entity for which prognosis and therapy remain poorly understood. In the current study, the authors investigated the effect of vascular endothelial growth factor (VEGF)-targeted therapy in this distinct subtype of RCC.

Methods: A retrospective review was conducted to describe the clinical characteristics and outcome of adult patients with metastatic Xp11.2 RCC who had strong TFE3 nuclear immunostaining and received anti-VEGF therapy. Tumor response to anti-VEGF therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions.

Results: Fifteen patients were identified, of whom 10, 3, and 2 received sunitinib, sorafenib, and monoclonal anti-VEGF antibodies, respectively. The median follow-up was 19.1 months, the median age of the patients was 41 years, and the female:male ratio was 4:1. Initial histologic description included clear cell (n = 8 patients), papillary (n = 1 patient), or mixed clear cell/papillary RCC (n = 6 patients). Five patients had received prior systemic therapy. Five patients had undergone fluorescent in situ hybridization analysis and all demonstrated a translocation involving chromosome Xp11.2. When treated with VEGF-targeted therapy, 3 patients achieved a partial response, 7 patients had stable disease, and 5 patients developed progressive disease. The median PFS and OS of the entire cohort were 7.1 months and 14.3 months, respectively.

Conclusions: Adult-onset, translocation-associated metastatic RCC is an aggressive disease that affects a younger population of patients with a female predominance. In the current study, VEGF-targeted agents appeared to demonstrate some efficacy.

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use*
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology
  • Chromosomes, Human, X*
  • Female
  • Humans
  • Indoles / therapeutic use*
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology
  • Male
  • Neoplasm Metastasis
  • Pyrroles / therapeutic use*
  • Sunitinib
  • Translocation, Genetic*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*


  • Antineoplastic Agents
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Indoles
  • Pyrroles
  • TFE3 protein, human
  • Vascular Endothelial Growth Factor A
  • Sunitinib