非小细胞肺癌组织中P27表达及定位与磷酸化AKT的关系

Correlation of P27 Expression and Localization to Phosphorylated AKT in Non-small Cell Lung Cancer

背景与目的:抑癌基因的失活在肿瘤的发生发展中有重要作用。p27的失活包括P27表达的减少或丢失及P27的胞浆错定位。AKT是一种丝氨酸/苏氨酸激酶,活化状态的AKT[磷酸化AKT(phosphorylatedAKT),p-AKT]能够调节细胞周期中的多个效应分子,其中包括对P27表达及定位的调节。本研究旨在探讨P27在非小细胞肺癌中(NSCLC)中的表达、定位及与p-AKT之间的相关性。方法:应用免疫组化的方法,分别检测NSCLC组织80例、非肿瘤性肺组织标本35例中P27蛋白的核、浆表达及磷酸化AKT的表达,并对它们与临床病理因素的相关性进行分析。结果:在NSCLC组织中,P27蛋白总阳性率为72.5%,其中胞核阳性率为46.3%;在非肿瘤性肺组织中P27总阳性率及胞核阳性率均为94.3%,两组对比P27总阳性率及胞核阳性率差异均有显著性意义(P<0.01)。80例NSCLC中有21例呈现单纯胞浆阳性;而在非肿瘤性肺组织中未见单纯胞浆阳性表达,两组对比差异有显著性意义(P<0.01)。P27的胞核表达在无淋巴结转移组和病理高、中分化组明显高于淋巴结转移组、低分化组的表达,组间比较差别具有显著性意义(P<0.05);P27的胞核表达与患者年龄、性别、肿瘤类型、TNM分期无关(P>0.05)。P27的胞浆表达与临床病理特征无关(P>0.05)。p-AKT蛋白在NSCLC中阳性表达率为78.8%,在非肿瘤性肺组织中呈阴性表达,两组之间差异有显著性意义(P<0.05);p-AKT在腺癌高、中分化组的表达(95.0%)高于低分化组的表达(50.0%)(P<0.01)。在NSCLC中,p-AKT的表达与P27胞浆表达呈正相关(r=0.437,P<0.01);p-AKT的表达与P27胞核表达无相关关系(r=0.175,P>0.05)。结论:NSCLCP27胞核表达的减少或丢失可能与肺癌的恶性发展有关;NSCLC中P27单纯性胞浆表达可能是肺癌细胞表达的特征之一;磷酸化AKT可能参与了对P27胞浆定位的调节,但与P27胞核表达无明显相关关系。

BACKGROUND ＆ OBJECTIVE. Inactivation of tumor suppressor gene plays an important role in tumorigenesis and tumor development, Functional inactivation of the tumor suppressor gene p27 in human cancer occurs either through the loss of expression or through phosphorylation-dependent cytoplasmic mislocalization. AKT, known as protein kinase B, represents a subfamily of serine/threonine protein kinases. Activated AKT （phosphorylated AKT, p-AKT） could promote cell cycle progression by modulating many effectors in cell cycle, including the expression and localization of P27. This study was to investigate the expression and localization of P27 protein in human non-small cell lung cancer （NSCLC）, and further to explore its correlation to p-AKT, METHODS. The expression and subcellular localization of P27 and the expression of p-AKT in 80 cases of NSCLC and 35 cases of non-cancerous lung disease were detected by immunohistochemistry, and their correlations to cliniopathologic factors were statistically analyzed. RESULTS. The total and nuclear positive rates of p27 were significantly lower in NSCLC than in noncancerous lung disease （72.5% vs. 94,3%, 46.3% vs. 94.3%, P〈0.01）. There were 21 cases of NSCLC with only cytoplasmic expression of P27, while no cytoplasmic expression alone was found in 35 cases of noncancerous lung disease （P〈0.01）, The nuclear positive rate of P27 was significantly higher in NSCLC without lymph node metastasis than in NSCLC with lymph node metastasis （P〈0.05）, and higher in well- and moderatelydifferentiated NSCLC than in poorly-differentiated NSCLC （P〈0.05）. The nuclear and cytoplasmic expression of P27 has no correlation to cliniopathologic factors of NSCLC （P〉0,05）. The positive rate of p-AKT was significantly higher in NSCLC than in non-cancerous lung disease （78.8% vs. 0, P〈0.05）; it was significantly higher in well- and moderately-differentiated adenocarcinoma than in poorly-differentiated adenocarcinoma （95.0% vs. 50.0%, P〈0.05）. In NSCLC, the expression of p-AKT was positively correlated to the cytoplasmic expression of P27 （r=0.437, P〈0.01）, but had no correlation to the nuclear expression of P27 （r=0.175, P〉0.05）. CONCLUSIONS： Reduced nuclear expression or loss of expression of P27 may be associated to the development of NSCLC. The localization of P27 only in cytoplasm may be one of the characteristics of lung cancer cells. P-AKT might play a role in the cytoplasmic localization of P27, but has no correlation to its nuclear expression.