The prognostic impact of Akt isoforms, PI3K and PTEN related to female steroid hormone receptors in soft tissue sarcomasReportar como inadecuado

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Journal of Translational Medicine

, 9:200

Cancer microenvironment


BackgroundThe PI3K-Akt pathway is involved in cellular survival pathways by inhibiting apoptotic processes and stimulating cell growth and proliferation. Its negative prognostic value has been proven in many types of cancer. In soft tissue sarcomas, the expression profiles of the PI3K-Akt pathway components are poorly defined and their significance uncertain. We aimed to investigate the prognostic impact of Akt Akt1 phosphorylated at threonine and serine, Akt2, Akt3, PI3K and PTEN, alone and in coexpression with ER and PgR in non-gastrointestinal stromal tumor soft tissue sarcomas non-GIST STSs.

Patients and methodsTumor samples and clinical data from 249 patients with non-GIST STS were obtained, and tissue microarrays TMAs were constructed. Immunohistochemistry IHC was used to evaluate marker expression in tumor cells.

ResultsIn univariate analyses, the expression levels of p-Akt Thr P = 0.002, Akt2 P = 0.008 and PI3K P < 0.001 were significant prognostic factors. In the multivariate analysis, high PI3K expression was an independent negative prognosticator HR = 1.5, 95% CI = 1.0-2.2, P = 0.042 in addition to advanced age, tumor depth, high malignancy grade, metastasis at diagnosis, surgery and positive resection margins. p-Akt Thr expression had strong unfavorable effect in men only P = 0.009. In contrast, p-Akt Ser expression had strong unfavorable impact in women P = 0.023. PgR-p-Akt Ser+ phenotype tended to have less favorable impact in women P = 0.087, but was the most favorable one in men P = 0.010.

ConclusionExpression of PI3K was significantly associated with aggressive behavior and shorter DSS in non-GIST STSs. The site of Akt phosphorylation seems to have gender-dependent impact on survival in STS patients.

Keywordssoft tissue sarcomas Akt isoforms PI3K PTEN ER PgR disease-specific survival Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-9-200 contains supplementary material, which is available to authorized users.

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Autor: Andrej Valkov - Thomas K Kilvaer - Sveinung W Sorbye - Tom Donnem - Eivind Smeland - Roy M Bremnes - Lill-Tove Busund


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