Involvement of the PI3K/Akt pathway in myxoid/round cell liposarcoma

Mod Pathol. 2012 Feb;25(2):212-21. doi: 10.1038/modpathol.2011.148. Epub 2011 Oct 21.


The molecular determinants involved in the progression of myxoid liposarcoma to increased cellularity/round cell change are poorly understood. We studied the PI3K/Akt pathway in myxoid and round cell liposarcomas using a tissue microarray composed of 165 tumors from 111 patients, and mutational analysis of PIK3CA in 44 cases. Activating PIK3CA mutations were found in 6/44 cases, 14%; mutations were more frequent in round cell vs myxoid tumors (5/15, 33% vs 1/29, 3%; P=0.013). Complete loss of PTEN, an alternative mechanism for PI3K/Akt activation, was found in 13/111 (12%) cases and was mutually exclusive with PIK3CA mutation. Strong IGF1R expression was demonstrated in 14/39 (36%) of round cell and 11/58 (19%) of myxoid tumors (P=0.062). Activation of the PI3K pathway was confirmed using immunohistochemical analysis for downstream targets phospho-S6 ribosomal protein and phospho-4EBP1. Phospho-4EBP1 was increased in round cell tumors compared with myxoid tumors (24/30, 80% vs 25/44, 57%; P=0.038) or tumors with treatment effect (10/24, 42%; P=0.02). Phospho-S6 was highly expressed in both myxoid and round cell tumors (29/47, 62% and 14/30, 47%, respectively; P=0.2). In tumors with PIK3CA mutation, any IGF1R expression, or loss of PTEN expression, phospho-4EBP1 was more frequently elevated compared with tumors without a known activating event in the PI3K pathway (55/72; 76% vs 3/8, 38%; P=0.033). These findings suggest that activation of the PI3K/Akt pathway via activating mutation of PIK3CA, loss of PTEN, or IGF1R expression have a role in round cell transformation. The PI3K/Akt pathway may therefore provide a therapeutic target in round cell liposarcoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cell Transformation, Neoplastic / genetics
  • Class I Phosphatidylinositol 3-Kinases
  • Female
  • Genotype
  • Humans
  • Liposarcoma, Myxoid / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation
  • PTEN Phosphohydrolase / genetics*
  • Phosphatidylinositol 3-Kinases / genetics*
  • Proto-Oncogene Proteins c-akt / genetics
  • Receptor, IGF Type 1 / genetics*
  • Signal Transduction* / genetics
  • Soft Tissue Neoplasms / genetics*
  • Young Adult


  • Membrane Proteins
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt
  • TPTE protein, human
  • PTEN Phosphohydrolase