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

Elizabeth G. Demicco, Keila E. Torres, Markus P. Ghadimi, Chiara Colombo, Svetlana Bolshakov, Aviad Hoffman, Tingsheng Peng, Judith V M G Bovée, Wei Lien Wang, Dina Lev, Alexander J. Lazar

Research output: Contribution to journalArticle

Abstract

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; P0.2). 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.

Original languageEnglish
Pages (from-to)212-221
Number of pages10
JournalModern Pathology
Volume25
Issue number2
DOIs
Publication statusPublished - Feb 2012

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Liposarcoma
Phosphatidylinositol 3-Kinases
Neoplasms
Mutation
Myxoid Liposarcoma
Ribosomal Protein S6
S 6

Keywords

  • IGF1R
  • myxoid liposarcoma
  • PI3K
  • PTEN
  • round cell liposarcoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Demicco, E. G., Torres, K. E., Ghadimi, M. P., Colombo, C., Bolshakov, S., Hoffman, A., ... Lazar, A. J. (2012). Involvement of the PI3K/Akt pathway in myxoid/round cell liposarcoma. Modern Pathology, 25(2), 212-221. https://doi.org/10.1038/modpathol.2011.148

Involvement of the PI3K/Akt pathway in myxoid/round cell liposarcoma. / Demicco, Elizabeth G.; Torres, Keila E.; Ghadimi, Markus P.; Colombo, Chiara; Bolshakov, Svetlana; Hoffman, Aviad; Peng, Tingsheng; Bovée, Judith V M G; Wang, Wei Lien; Lev, Dina; Lazar, Alexander J.

In: Modern Pathology, Vol. 25, No. 2, 02.2012, p. 212-221.

Research output: Contribution to journalArticle

Demicco, EG, Torres, KE, Ghadimi, MP, Colombo, C, Bolshakov, S, Hoffman, A, Peng, T, Bovée, JVMG, Wang, WL, Lev, D & Lazar, AJ 2012, 'Involvement of the PI3K/Akt pathway in myxoid/round cell liposarcoma', Modern Pathology, vol. 25, no. 2, pp. 212-221. https://doi.org/10.1038/modpathol.2011.148
Demicco EG, Torres KE, Ghadimi MP, Colombo C, Bolshakov S, Hoffman A et al. Involvement of the PI3K/Akt pathway in myxoid/round cell liposarcoma. Modern Pathology. 2012 Feb;25(2):212-221. https://doi.org/10.1038/modpathol.2011.148
Demicco, Elizabeth G. ; Torres, Keila E. ; Ghadimi, Markus P. ; Colombo, Chiara ; Bolshakov, Svetlana ; Hoffman, Aviad ; Peng, Tingsheng ; Bovée, Judith V M G ; Wang, Wei Lien ; Lev, Dina ; Lazar, Alexander J. / Involvement of the PI3K/Akt pathway in myxoid/round cell liposarcoma. In: Modern Pathology. 2012 ; Vol. 25, No. 2. pp. 212-221.
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