Kim T-J, Lee J-W, Song S Y, Choi J-J, Choi C H, Kim B-G, Lee J-H, Bae D-S
Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-gu, Seoul 135-710, Korea.
Br J Cancer. 2006 Jun 5;94(11):1678-82. doi: 10.1038/sj.bjc.6603180.
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.
磷酸化AKT(pAKT)是人类癌症放射抗性的主要促成因素。本研究的目的是调查pAKT表达与宫颈癌放射抗性之间的关联。对27例因局部晚期宫颈癌(LACC,国际妇产科联盟(FIGO)分期为IIB-IVA期)接受初次放射治疗的女性患者的记录进行了回顾性分析。9例被视为放射抗性的患者出现局部复发,无进展生存期的中位数为9个月。18例未出现局部复发,被视为放射敏感组。我们使用预处理的石蜡包埋组织,通过免疫组织化学评估pAKT表达。发现pAKT表达水平与局部复发之间存在显著关联。pAKT免疫组织化学染色在放射抗性组中比在放射敏感组中显著更频繁(P=0.004)。pAKT阴性染色患者(19例)的平均无进展生存期为86个月,pAKT阳性表达患者(8例)的平均无进展生存期为44个月(P=0.008)。这些结果表明,磷脂酰肌醇3激酶/pAKT信号传导可导致放射抗性,并且pAKT评估可能是LACC患者对放疗反应的预后标志物。