Chen Hao, Zhang Kai, Wu Guizhong, Song Dawei, Chen Kangwu, Yang Huilin
Department of Orthopedics, The First Affiliated Hospital of Soochow University Suzhou, China.
Int J Clin Exp Pathol. 2015 Nov 1;8(11):14741-8. eCollection 2015.
Sacral chordoma is a rare spine tumor with a high recurrence rate even after optimal therapy. Previous studies have demonstrated that the PI3K/AKT pathway plays a pivotal role in chordoma, and high expression of pAKT is associated with poor prognosis. Recently, PHLPP was recognized to be a tumor suppressor that targets AKT. We analyzed the expression of PHLPP1 and AKT2 in 37 chordoma samples and 11 fetal nucleus pulposus samples by immunohistochemical staining. Of the chordoma cases, 40.5% (15/37) showed strong cytoplasmic staining (score ≥3) for PHLPP1, which was significantly lower than the 90.9% (10/11) of fetal nucleus pulposus samples (P = 0.004). Conversely, strong immunohistochemical staining for AKT2 was observed in 75.7% (28/37) of chordoma samples, which was significantly higher than 36.4% (4/11) of fetal nucleus pulposus (P = 0.021). Kaplan-Meier survival curves and log-rank test showed that patients with high expression of PHLPP1 experienced longer progression free survival time than those with low PHLPP1 expression (P = 0.011). Further multivariate Cox regression analysis indicated that PHLPP1 expression level and surgical approaches were independent risk factors for chordoma recurrence (P = 0.023 and P = 0.022). However, PHLPP1 expression was not statistically related to patients' total survival time. Conclusively, our results suggest that PHLPP1 plays a crucial role in sacral chordoma, and may be a promising biomarker for prognosis. Meanwhile, manipulation of PHLPP1 expression is also a potential therapeutic approach for the treatment of sacral chordoma.
骶骨脊索瘤是一种罕见的脊柱肿瘤，即使经过最佳治疗，其复发率仍很高。先前的研究表明，PI3K/AKT通路在脊索瘤中起关键作用，pAKT的高表达与预后不良相关。最近，PHLPP被认为是一种靶向AKT的肿瘤抑制因子。我们通过免疫组织化学染色分析了37例脊索瘤样本和11例胎儿髓核样本中PHLPP1和AKT2的表达。在脊索瘤病例中，40.5%（15/37）的PHLPP1显示强细胞质染色（评分≥3），这显著低于胎儿髓核样本的90.9%（10/11）（P = 0.004）。相反，75.7%（28/37）的脊索瘤样本中观察到AKT2的强免疫组织化学染色，这显著高于胎儿髓核的36.4%（4/11）（P = 0.021）。Kaplan-Meier生存曲线和对数秩检验显示，PHLPP1高表达的患者无进展生存期长于PHLPP1低表达的患者（P = 0.011）。进一步的多变量Cox回归分析表明，PHLPP1表达水平和手术方式是脊索瘤复发的独立危险因素（P = 0.023和P = 0.022）。然而，PHLPP1表达与患者的总生存时间无统计学相关性。总之，我们的结果表明，PHLPP1在骶骨脊索瘤中起关键作用，可能是一种有前景的预后生物标志物。同时，调控PHLPP1表达也是治疗骶骨脊索瘤的一种潜在治疗方法。
