Tomita Yasuhiko, Morooka Takaya, Hoshida Yoshihiko, Zhang Binglin, Qiu Ying, Nakamichi Itsuko, Hamada Ken-Ichiro, Ueda Takafumi, Naka Norifumi, Kudawara Ikuo, Aozasa Katsuyuki
Department of Pathology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Clin Cancer Res. 2006 May 15;12(10):3070-7. doi: 10.1158/1078-0432.CCR-05-1732.
AKT is a serine/threonine kinase which is important in tumorigenesis. Several molecules involved in AKT pathway are dysregulated in various kinds of human cancers.
Ninety-three patients (53 males and 40 females), ages ranging from 19 to 77 years (median, 57 years), with localized soft-tissue sarcomas arising in the trunk and extremities, were analyzed. Immunoperoxidase procedure (avidin-biotin complex method) was done on paraffin-embedded sections with anti-phosphorylated AKT (Thr308), anti-phosphorylated p44/42 extracellular signal-regulated kinase 1 and 2 (ERK1/2) (Thr202/Tyr204), anti-phosphorylated forkhead in rhabdomyosarcoma (FKHR) (Ser256), and anti-Ki 67 antibodies. Expression levels of phosphorylated AKT (p-AKT), phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated FKHR (p-FKHR) were categorized as either weaker (level 1) or equal to or stronger (level 2) compared with those in the endothelial cells of the same specimens. Percentage of cells showing intranuclear staining with Ki-67 was shown as the Ki-67 labeling index (LI). Cases were divided into two groups: level 1, Ki-67 LI < 20%; level 2, Ki-67 LI > or = 20%.
Twenty-six (28.0%), 6 (6.5%), and 46 (44.1%) of the tumors showed level 2 expression for p-AKT, p-ERK1/2, and Ki-67 LI, respectively. Tumors with level 2 p-AKT expression showed a higher ratio of level 2 p-FKHR expression (P < 0.01). Multivariate analysis revealed p-AKT expression and Ki-67 LI to be independent prognosticators for overall survival, and p-AKT expression for disease-free survival.
p-AKT expression level is a significant prognosticator in soft-tissue sarcoma.
AKT是一种丝氨酸/苏氨酸激酶，在肿瘤发生过程中起重要作用。多种参与AKT信号通路的分子在各类人类癌症中表达失调。
对93例患者（53例男性，40例女性）进行分析，年龄范围为19至77岁（中位数为57岁），均患有发生于躯干和四肢的局限性软组织肉瘤。采用免疫过氧化物酶法（抗生物素蛋白-生物素复合物法），对石蜡包埋切片使用抗磷酸化AKT（苏氨酸308）、抗磷酸化p44/42细胞外信号调节激酶1和2（ERK1/2）（苏氨酸202/酪氨酸204）、抗磷酸化横纹肌肉瘤叉头蛋白（FKHR）（丝氨酸256）以及抗Ki-67抗体进行检测。将磷酸化AKT（p-AKT）、磷酸化ERK1/2（p-ERK1/2）和磷酸化FKHR（p-FKHR）的表达水平与同一样本中内皮细胞的表达水平相比较，分为较弱（1级）或等于或较强（2级）。显示细胞核内有Ki-67染色的细胞百分比作为Ki-67标记指数（LI）。病例分为两组：1级，Ki-67 LI<20%；2级，Ki-67 LI≥20%。
分别有26例（28.0%）、6例（6.5%）和46例（44.1%）肿瘤显示p-AKT、p-ERK1/2和Ki-67 LI的2级表达。p-AKT表达为2级的肿瘤显示2级p-FKHR表达的比例更高（P<0.01）。多因素分析显示，p-AKT表达和Ki-67 LI是总生存的独立预后因素，p-AKT表达是无病生存的独立预后因素。
p-AKT表达水平是软组织肉瘤的一个重要预后因素。
