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

Journal of Translational Medicine

Research

Sveinung W Sorbye¹  Lill-Tove Busund¹  Andrej Valkov¹  Eivind Smeland²  Roy M Bremnes³  Tom Donnem³  Thomas K Kilvaer⁴ 

[1] Dept of Clinical Pathology, University Hospital of Northern Norway, Tromsø, Norway;Institute of Medical Biology, University of Tromsø, Norway;Dept of Oncology, University Hospital of Northern Norway, Tromsø, Norway;Dept of Oncology, University Hospital of Northern Norway, Tromsø, Norway;Institute of Clinical Medicine, University of Tromsø, Norway;Institute of Medical Biology, University of Tromsø, Norway;

关键词: soft tissue sarcomas;    Akt isoforms;    PI3K;    PTEN;    ER;    PgR;    disease-specific survival;   

DOI  :  10.1186/1479-5876-9-200

 received in 2011-07-30, accepted in 2011-11-22,  发布年份 2011

来源: Springer

【 摘 要 】

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 threonine308 and serine473, 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 Thr308 (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 Thr308 expression had strong unfavorable effect in men only (P = 0.009). In contrast, p-Akt Ser473 expression had strong unfavorable impact in women (P = 0.023). PgR-/p-Akt Ser473+ 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.

【 授权许可】

CC BY   
© Valkov et al; licensee BioMed Central Ltd. 2011