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

Journal of Translational Medicine

Lill-Tove Busund²  Roy M Bremnes³  Eivind Smeland¹  Tom Donnem³  Sveinung W Sorbye²  Thomas K Kilvaer²  Andrej Valkov² 

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

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

Others  :  1207818
DOI  :  10.1186/1479-5876-9-200

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

【 摘 要 】

Background

The 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 methods

Tumor 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.

Results

In 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).

Conclusion

Expression 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】

   
2011 Valkov et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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