Clinical heterogeneity of Xp11 translocation renal cell carcinoma: impact of fusion subtype, age, and stage

Mod Pathol. 2014 Jun;27(6):875-86. doi: 10.1038/modpathol.2013.208. Epub 2013 Dec 6.

Abstract

Xp11 translocation renal cell carcinomas harbor chromosome translocations involving the Xp11 breakpoint, resulting in gene fusions involving the TFE3 gene. The most common subtypes are the ASPSCR1-TFE3 renal cell carcinomas resulting from t(X;17)(p11;q25) translocation, and the PRCC-TFE3 renal cell carcinomas, resulting from t(X;1)(p11;q21) translocation. A formal clinical comparison of these two subtypes of Xp11 translocation renal cell carcinomas has not been performed. We report one new genetically confirmed Xp11 translocation renal cell carcinoma of each type. We also reviewed the literature for all published cases of ASPSCR1-TFE3 and PRCC-TFE3 renal cell carcinomas and contacted all corresponding authors to obtain or update the published follow-up information. Study of two new, unpublished cases, and review of the literature revealed that 8/8 patients who presented with distant metastasis had ASPSCR1-TFE3 renal cell carcinomas, and all but one of these patients either died of disease or had progressive disease. Regional lymph nodes were involved by metastasis in 24 of the 32 ASPSCR1-TFE3 cases in which nodes were resected, compared with 5 of 14 PRCC-TFE3 cases (P=0.02).; however, 11 of 13 evaluable patients with ASPSCR1-TFE3 renal cell carcinomas who presented with N1M0 disease remained disease free. Two PRCC-TFE3 renal cell carcinomas recurred late (at 20 and 30 years, respectively). In multivariate analysis, only older age or advanced stage at presentation (not fusion subtype) predicted death. In conclusion, ASPSCR1-TFE3 renal cell carcinomas are more likely to present at advanced stage (particularly node-positive disease) than are PRCC-TFE3 renal cell carcinomas. Although systemic metastases portend a grim prognosis, regional lymph node involvement does not, at least in short-term follow-up. The tendency for PRCC-TFE3 renal cell carcinomas to recur late warrants long-term follow-up.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adolescent
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology*
  • Cell Cycle Proteins / genetics
  • Chromosomes, Human, X / genetics
  • Female
  • Genetic Heterogeneity
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology*
  • Male
  • Neoplasm Proteins / genetics
  • Neoplasm Staging
  • Oncogene Proteins, Fusion / genetics*
  • Translocation, Genetic*

Substances

  • ASPSCR1 protein, human
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Oncogene Proteins, Fusion
  • PRCC protein, human
  • TFE3 protein, human