Proliferative and apoptotic differences between alveolar rhabdomyosarcoma subtypes: a comparative study of tumors containing PAX3-FKHR or PAX7-FKHR gene fusions

Med Pediatr Oncol. 2001 Aug;37(2):83-9. doi: 10.1002/mpo.1174.


Background: Most alveolar rhabdomyosarcomas (ARMS) have chromosome translocations and resultant gene fusion products. The more common translocation fuses the PAX3 and FKHR genes; patients who have PAX3-FKHR-positive ARMS have reduced event-free survival compared to patients with ARMS containing the less common translocation that fuses the PAX7 and FKHR genes.

Procedure: We examined histology, immunohistochemical markers of differentiation, and cell cycle characteristics of a panel of ARMS containing either PAX3-FKHR or PAX7-FKHR transcript to determine if these features differ between the ARMS subsets.

Results: Cell cycle parameters varied significantly: the number of nuclei that stained with either an immunohistochemical marker of proliferation (MIB1), or a TUNEL-based assay for apoptosis was significantly greater in tumors that expressed PAX3-FKHR compared to tumors that expressed PAX7-FKHR transcript.

Conclusions: We conclude that compared to PAX7-FKHR-containing tumors, ARMS that contain PAX3-FKHR transcript have (1) increased cell proliferation, consistent with greater loss of cell cycle regulation, and (2) apoptosis that is increased but insufficient to prevent tumor formation. More marked cell cycle dysregulation may contribute to poorer prognosis for patients with ARMS that have PAX3-FKHR fusion. Med Pediatr Oncol 2001;37:83-89.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis*
  • Artificial Gene Fusion*
  • Cell Cycle*
  • Cell Division*
  • Child
  • Child, Preschool
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins / genetics*
  • Disease-Free Survival
  • Female
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Neoplastic
  • Homeodomain Proteins / genetics*
  • Humans
  • Immunohistochemistry
  • Male
  • PAX7 Transcription Factor
  • Paired Box Transcription Factors
  • Prognosis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhabdomyosarcoma, Alveolar / genetics*
  • Rhabdomyosarcoma, Alveolar / physiopathology*
  • Transcription Factors / genetics*
  • Translocation, Genetic


  • DNA, Neoplasm
  • DNA-Binding Proteins
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Homeodomain Proteins
  • PAX4 protein, human
  • PAX7 Transcription Factor
  • PAX7 protein, human
  • Paired Box Transcription Factors
  • Transcription Factors