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Involvement of the PI3K/Akt Pathway in Myxoid/Round Cell Liposarcoma

The molecular determinates 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 anal...

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Detalles Bibliográficos
Autores principales: Demicco, Elizabeth G., Torres, Keila E., Ghadimi, Markus, Colombo, Chiara, Bolshakov, Svetlana, Hoffman, Aviad, Peng, Tingsheng, Bovée, Judith V. M. G., Wang, Wei-lien, Lev, Dina, Lazar, Alexander J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266971/
https://www.ncbi.nlm.nih.gov/pubmed/22020193
http://dx.doi.org/10.1038/modpathol.2011.148
Descripción
Sumario:The molecular determinates 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 to 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 to 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 play a role in round cell transformation. The PI3K/Akt pathway may therefore provide a therapeutic target in round cell liposarcoma.