Increased expression of pAKT is associated with radiation resistance in cervical cancer

Abstract

Phosphorylated AKT (pAKT) is a major contributor to radioresistance in human cancers. The aim of this study was to investigate the association of pAKT expression and radiation resistance in cervical cancer. A retrospective review was made of the records of 27 women who received primary radiation therapy due to locally advanced cervical cancer (LACC) with FIGO stage IIB-IVA. Nine patients regarded as radiation resistant developed local recurrences with a median progression free interval of 9 months. Eighteen patients did not show local recurrences, and were regarded as a radiation-sensitive group. Using pretreatment paraffin-embedded tissues, we evaluated pAKT expression by immunohistochemistry. A significant association was found between the level of pAKT expression and local recurrence. Immunohistochemical staining for pAKT was significantly more frequent in the radiation-resistant than in the radiation-sensitive group (P=0.004). The mean progression-free survival was 86 months for patients with pAKT-negative staining (19 cases) and 44 months for patients with pAKT-positive expression (eight cases) (P=0.008). These results suggest that signalling from phosphatidylinositide 3-kinase/pAKT can lead to radiation resistance, and that evaluation of pAKT may be a prognostic marker for response to radiotherapy in LACC.

Figure 1

Representative examples of pAKT staining in cervical cancer. (A) No staining; (B) <50% with weak intensity (1+); (C) more than 50% with weak or moderate intensity (2+); (D) more than 50% with strong intensity (3+) (A–C, × 200; D, × 100).

Figure 2

Univariate progression-free survival (PFS) analysis of pAKT expression in 27 cases of locally advanced cervical cancer. The ‘pAKT positive’ expression in pretreatment biopsies is a poor prognostic factor for PFS (P=0.008).