Altered expression of key cell cycle regulators in renal cell carcinoma associated with Xp11.2 translocation

Pathol Res Pract. 2009;205(7):466-72. doi: 10.1016/j.prp.2009.01.005. Epub 2009 Feb 25.

Abstract

Renal cell carcinoma (RCC) is a rare tumor in the pediatric population. Recently, a phenotypically and genetically distinct kidney carcinoma, mainly prevalent in children and associated with an Xp11.2 translocation or TFE3 gene fusion, has been described. It has been advanced that in this subtype of RCC, there is an accumulation of cyclin D1, cyclin D3, and p21 ((wafl/cip1)). The aim of the present study was to figure out in two pediatric RCC recently diagnosed in our department (one clear cell-type RCC and one TFE3-positive RCC) whether those features are indeed specific of the latter tumor or occur in pediatric RCC irrespective of the tumor type. The following immunostains were performed in both cases: Ki67, p16(ink4a), p21 ((wafl/cip1)), p27(kip1), p53, p63, mdm2, cyclin D1, cyclin D3, TFE3, CD10, vimentin, E-cadherin, and RCC-antigen. We observed in the TFE3-positive carcinoma an intense immunoreaction for p21 ((wafl/cip1)), cyclin D1, and cyclin D3, without expression for p53, p16, p27(kip1), and mdm2, whereas the immunoexpression profile observed in the classic RCC was similar to that of clear cell, adult-type RCC. Our study confirms that TFE3-positive RCC exhibits a deregulation of the cell cycle apparently unrelated to the young age of the patients.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics*
  • Carcinoma, Renal Cell / chemistry*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / therapy
  • Cell Cycle Proteins / analysis*
  • Child
  • Chromosomes, Human, X*
  • Cyclin D1 / analysis
  • Cyclin D3
  • Cyclin-Dependent Kinase Inhibitor p21 / analysis
  • Cyclins / analysis
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genotype
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Infant
  • Kidney Neoplasms / chemistry*
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy
  • Nephrectomy
  • Phenotype
  • Translocation, Genetic*
  • Treatment Outcome

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • CCND1 protein, human
  • CCND3 protein, human
  • CDKN1A protein, human
  • Cell Cycle Proteins
  • Cyclin D3
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • TFE3 protein, human
  • Cyclin D1