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

作者：Demicco Elizabeth G; Torres Keila E; Ghadimi Markus P; Colombo Chiara; Bolshakov Svetlana; Hoffman Aviad; Peng Tingsheng; Bovee Judith V M G; Wang Wei Lien; Lev Dina; Lazar Alexander J^*

来源：Modern Pathology, 2012, 25(2): 212-221.

DOI：10.1038/modpathol.2011.148

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

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/Aid 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. Modern Pathology (2012) 25, 212-221; doi:10.1038/modpathol.2011.148; published online 21 October 2011

• 出版日期2012-2