抑癌基因PTEN在非小细胞肺癌发生发展中的作用

The Role of PTEN in the Process of Non-Small Cell Lung Cancer

目的 研究抑癌基因 10q丢失的与张力蛋白同源的磷酸酶基因 (PTEN)在非小细胞肺癌 (NSCLC)组织中的表达水平与NSCLC的发生和发展的关系 ,以及PTEN和抑癌基因p2 7Kip1、细胞周期蛋白D1(CyclinD1)表达的相关性。方法 以免疫组化方法分别检测 6 2例石蜡包埋的NSCLC组织中PTEN、p2 7Kip1和CyclinD1蛋白表达水平 ;用原位杂交方法检测 2 1例新鲜NSCLC组织中PTENmRNA的表达情况。结果 PTEN的表达在肺鳞癌中阳性率为4 0 0 % ( 12 / 30 ) ,肺腺癌中为 4 3 75 % ( 14 / 32 ) ;中高分化组肺癌中阳性率为 5 4 2 9% ( 19/ 35 ) ,低分化组中为2 5 93% ( 7/ 2 7) ;淋巴结转移组阳性率为 4 0 91% ( 9/ 2 2 ) ,无转移组阳性率为 5 4 84 % ( 17/ 31)。 2 1例新鲜肺癌标本原位杂交结果显示 ,鳞癌阳性率为 4 1 6 7% ( 5 / 12 ) ,腺癌阳性率为 33 33% ( 3/ 9)。同时检测了 p2 7Kip1和CyclinD1在肺癌中的表达状况。PTEN与p2 7Kip1表达呈正相关 ( χ2 =4 2 6 6 6 7,P <0 0 5 ) ,与CyclinD1的表达呈负相关 ( χ2 =4 5 5 814 ,P <0 0 5 )。结论 PTEN的失表达在NSCLC的发生、发展和转移过程中扮演着重要的角色。其失表达与NSCLC的分化程度 (P <0 0 5 )、淋巴结转移 (P <0 0 5 )有关 ,而与其组织学类型无关 (P >0

Objective To detect the expression of phosphatase and tensin homology deleted on chromosome ten (PTEN) in the tissues of non small cell lung cancer (NSCLC) to reveal the role of PTEN in the process of NSCLC and also the relationship of PTEN and p27 Kip1 , Cyclin D 1. Methods In 62 formalin fixed and paraffin embedded human NSCLC specimens and 21 freezing fresh specimens, immunohistochemisty and in situ hybridization (ISH) were performed to detect the protein level of PTEN, p27 Kip1 and Cyclin D 1, and the mRNA level of PTEN gene respectively. Results Among the 62 paraffin embedded specimens, the positive rate of PTEN staining was 40 0 %(12/30)and 43 75 % (14/32) in lung squamous carcinoma and adenocarcinoma specimens respectively; In high and middle differentiation grade group, the positive rate was 54 29 %(19/35)and in low grade, it was 25 93 %(7/27); In lymph node metastasis group, the positive rate was 40 91 %(9/22)and in the group without lymph node metastasis, it was 54 84 % (17/31). At the same time, the expression of p27 Kip1 and Cyclin D 1 was also detected and the results were similar among the 21 freezing fresh specimens. ISH showed that the positive rate of PTEN mRNA was 41 67 %(5/12)and 33 33 % (3/9)in squamous carcinoma and adenocarcinoma respectively. Conclusion PTEN plays an important role in the occurrence and development of the NSCLC. The loss of expression of PTEN is associated with the differentiation grade and lymph node metastasis ( P <0 05) of NSCLC, but has no relation with the histological types. The expression of PTEN in NSCLC is positively related to p27 Kip1 , but negatively to Cyclin D 1.