Significance of Akt activation and AKT gene increases in soft tissue tumors.

[well-differentiated liposarcoma]

To clarify the aberrations of AKT genes , their protein products and clinicopathologic significance in bone and soft tissue tumors , expression profiles of total Akt , its isoforms and activated Akt , and increases in copy number of AKT 1 /AKT 2 genes were examined . Immunohistochemical analysis in 77 cases revealed overexpression of total Akt , Akt 1 , Akt 2 , and phosphorylated Akt in 84 .4 %, 67 .5 %, 72 .7 %, and 71 .4 %, respectively . Positive results were also observed in benign lesions but at a lower frequency . Overexpression of Akt 1 was more frequent than that of Akt 2 in well-differentiated liposarcoma (6 /7 versus 3 /7 cases ) and schwannoma (4 /4 versus 1 /4 cases ), whereas Akt 2 overexpression and Akt activation were more frequent than Akt 1 overexpression in malignant nerve sheath (3 /4 and 4 /4 , respectively , versus 2 /4 cases ) and muscular tumors (8 /9 and 8 /9 versus 4 /9 cases ). By fluorescence in situ hybridization analysis , increase of gene copy number was observed in 13 .3 % for AKT 1 and in 25 .0 % for AKT 2 due to polysomy of chromosome 14 or 19 , respectively , but not gene amplification . One case of schwannoma exhibited polysomy of both chromosomes 14 and 19 . Akt activation was correlated with total Akt cytoplasmic localization (P = .0031 ) and subsequent metastasis (P = .0454 ). Moreover , AKT 2 gene increase correlated with tumor size (P = .0352 ) and metastasis (P = .0344 ). In conclusion , in a defined subset of bone and soft tissue tumors , including benign tumors , Akt was frequently overexpressed and activated , and AKT 1 /2 copy number was increased . Because abnormality of Akt /AKT correlated with clinicopathologic profiles , novel therapies targeting isoform-specific Akts may be useful for these particular types of tumors .

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well-differentiated liposarcoma

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