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Hum Pathol ; 67: 60-68, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28711648

RESUMO

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous mesenchymal tumor of intermediate malignancy and fibroblastic/myofibroblastic differentiation. Fibrosarcomatous (FS) component is a high-grade component of DFSP. The detailed oncogenic difference between DFSP and FS components is not clear. We thus investigated the Akt-mTOR pathway in both components. We used 65 tumor samples obtained from 65 patients. The phosphorylation of Akt-mTOR pathway proteins (Akt, mTOR, 4EBP1, and S6RP) and PDGFRα/ß was assessed by immunohistochemical staining, the results of which were confirmed by Western blotting. The immunohistochemical results were as follows: in ordinary DFSP components, p-PDGFRα-positive tumors were 41.9% (18/43 cases), p-PDGFRß 55.8% (24/43 cases), p-Akt 51.2% (22/43 cases), p-mTOR 39.5% (17/43 cases), p-4EBP1 46.5% (20/43 cases), and p-S6RP 41.8% (18/43 cases); in DFSP components of FS-DFSP, 52.6% (10/19 cases), 47.4% (9/19 cases), 52.6% (10/19 cases), 36.8% (7/19 cases), 52.6% (10/19 cases), and 52.6% (10/19 cases); and in FS components, 45.5% (10/22 cases), 36.4% (8/22 cases), 72.7% (16/22 cases), 54.5% (12/22 cases), 72.7% (16/22 cases), and 68.2% (15/22 cases), respectively. There were significant positive correlations of the phosphorylation of most of the Akt-mTOR pathway proteins (p-Akt, p-mTOR, p-4EBP1, and p-S6RP) with each other (P < .05). Phospho-PDGFRß was well correlated with the phosphorylation of Akt-mTOR pathway proteins in DFSP components of ordinary and FS-DFSPs, but these correlations were weaker in FS components. This study suggested the association of activation of Akt-mTOR pathway proteins and PDGFR with the progression of DFSP to FS. The Akt-mTOR pathway is thus a potential therapeutic target in imatinib-resistant DFSP/FS.


Assuntos
Transformação Celular Neoplásica/química , Dermatofibrossarcoma/enzimologia , Proteínas Proto-Oncogênicas c-akt/análise , Receptor beta de Fator de Crescimento Derivado de Plaquetas/análise , Neoplasias Cutâneas/enzimologia , Serina-Treonina Quinases TOR/análise , Proteínas Adaptadoras de Transdução de Sinal/análise , Adolescente , Adulto , Idoso , Biópsia , Western Blotting , Proteínas de Ciclo Celular , Transformação Celular Neoplásica/metabolismo , Criança , Pré-Escolar , Dermatofibrossarcoma/patologia , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/análise , Fosforilação , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/análise , Proteínas Quinases S6 Ribossômicas/análise , Transdução de Sinais , Neoplasias Cutâneas/patologia , Adulto Jovem
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