Department of Pathology, Kyung Hee University School of Medicine, Seoul, Republic of Korea.
Pathobiology. 2012;79(2):84-93. doi: 10.1159/000334340. Epub 2012 Jan 27.
We investigated whether the expression of mammalian target of rapamycin (mTOR) pathway components is associated with clinicopathologic characteristics and patient outcome in lung adenocarcinoma (AC) and squamous cell carcinoma (SCC).
We used immunohistochemistry to evaluate the expression of phosphorylated Akt (pAkt), mTOR, p70 ribosomal protein S6 kinase (p70S6K) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in 91 cases of AC and 154 cases of SCC.
pAkt expression was positively correlated with the expression of mTOR (p < 0.001) and p70S6K (p < 0.001), and mTOR expression was positively correlated with p70S6K expression (p < 0.001). PTEN expression was inversely correlated with the expression of pAkt (p = 0.001), mTOR (p < 0.001) and p70S6K (p = 0.012). In addition, loss of PTEN expression, observed in 37.4% (34/91) of AC patients, was significantly associated with a higher histologic grade (p = 0.013), pathologic T stage (p = 0.016) and N stage (p < 0.001) and advanced TNM stage (p = 0.001), as well as a shorter overall survival of AC patients (p = 0.015).
The high prevalence of PTEN loss and its association with aggressive tumor behavior and poor patient outcome in AC suggest that loss of PTEN expression is involved in AC progression and serves as a prognostic marker for patients with AC.
我们研究了哺乳动物雷帕霉素靶蛋白(mTOR)通路成分的表达与肺腺癌(AC)和鳞状细胞癌(SCC)的临床病理特征和患者预后是否相关。
我们使用免疫组织化学方法评估了 91 例 AC 和 154 例 SCC 中磷酸化 Akt(pAkt)、mTOR、p70 核糖体蛋白 S6 激酶(p70S6K)和 10 号染色体缺失的磷酸酶和张力蛋白同源物(PTEN)的表达。
pAkt 表达与 mTOR(p<0.001)和 p70S6K(p<0.001)的表达呈正相关,mTOR 表达与 p70S6K 的表达呈正相关(p<0.001)。PTEN 表达与 pAkt(p=0.001)、mTOR(p<0.001)和 p70S6K(p=0.012)的表达呈负相关。此外,在 37.4%(34/91)的 AC 患者中观察到的 PTEN 缺失与更高的组织学分级(p=0.013)、病理 T 分期(p=0.016)、N 分期(p<0.001)和晚期 TNM 分期(p=0.001)显著相关,以及 AC 患者总生存期较短(p=0.015)。
PTEN 缺失的高发生率及其与 AC 侵袭性行为和患者不良预后的相关性表明,PTEN 缺失参与了 AC 的进展,并作为 AC 患者的预后标志物。