Clinical outcomes and differential effects of PI3K pathway mutation in obese versus non-obese patients with cervical cancer.

Clinical outcomes and differential effects of PI3K pathway mutation in obese versus non-obese patients with cervical cancer.

The purpose of this study was to evaluate the effect of obesity and obesity-associated factors on the outcomes of patients with cervical cancer. Outcomes were evaluated in 591 patients with FIGO Ib to IV cervical cancer treated uniformly with definitive radiation. Patients were stratified into 3 groups based upon pretreatment Body Mass Index (BMI): A ≤ 18.5; B 18.6 – 34.9; and C ≥ 35. The 5-year freedom from failure rates were 58, 59, and 73% for BMI groups A, B, and C (p = 0.01). Overall survival rates were 50, 59, and 68%, respectively (p = 0.02). High expression of phosphorylated AKT (pAKT) was associated with poor outcomes only in non-obese patients. Obese patients with PI3K pathway mutant tumors had a trend toward favorable outcomes, while a similar effect was not observed in non-obese patients. Compared to similar tumors from non-obese hosts, PIK3CA and PTEN mutant tumors from obese patients failed to express high levels of phosphorylated AKT and its downstream targets. These results show that patients with obesity at the time of diagnosis of cervical cancer exhibit improved outcomes after radiation. PI3K/AKT pathway mutations are common in obese patients, but are not associated with activation of AKT signaling.

本研究旨在评估肥胖及肥胖相关因素对宫颈癌患者预后的影响。对591例接受根治性放疗的国际妇产科联盟（FIGO）Ib - IV期宫颈癌患者进行了预后评估。根据治疗前体重指数（BMI）将患者分为3组：A组≤18.5；B组18.6 - 34.9；C组≥35。A、B、C组BMI患者的5年无失败生存率分别为58%、59%和73%（p = 0.01）。总生存率分别为50%、59%和68%（p = 0.02）。磷酸化AKT（pAKT）的高表达仅在非肥胖患者中与不良预后相关。PI3K通路突变肿瘤的肥胖患者有预后良好的趋势，而在非肥胖患者中未观察到类似效应。与非肥胖宿主的类似肿瘤相比，肥胖患者的PIK3CA和PTEN突变肿瘤未能表达高水平的磷酸化AKT及其下游靶点。这些结果表明，宫颈癌诊断时肥胖的患者在放疗后预后改善。PI3K/AKT通路突变在肥胖患者中常见，但与AKT信号的激活无关。