The Expression Of Survivin, P16INK4a In Non-Small Cell Lung Carcinoma And Their Significance

Objective:To study the expression of a novel inhibitor gene of apoptosis,survivin, in non-small cell lung carcinoma, and its relationship with theexpression of p16INK4a gene; To investigate the expression ofsurvivin,p16INK4a in fiberobronchoscopic aspirates and their valuation indiagnosis of non-small cell lung carcinoma.Methods:1. The immunohistochemistry was used to assay the expressionof survivin ,p16INK4a in tissues of fifty-six non-small cell lungcarcinomas.2. In situ hybyidization and immunocytochemistry was used todetect the mRNA and protein expression of survivin,p16INK4a in fibero-bronchoscopic aspirates exfoliated cells of sixty cases. The result wasanalyzed and compared.Results: 1. Survivin was expressed in 36 out of 56(64.3%) cases ofnon-small cell lung carcinomas. In contrast,only 8.3% in benign pulmonarydiseases(P<0.01). Overexpression of survivin was strongly related to thetumor grade, clinical TNM stages and the presence of mediastinal lymphnode metatases. 2. 51.8% cases of non-small cell lung carcinomas showeda negative p16INK4a protein expression and in only 16.7% of thepaired.There was significantly correlation between p16INK4a negativeexpression and the tumor grade, clinical TNM stages and the presence ofmediastinal lymph node metatases. 3.In p16INK4a positive expressiongroup and negative expression group,the positive rate of survivinexpression was 40.8%(11/27),86.2%(25/29),respectively.There was asiganificant statistical difference ( P<0.01 ) .An inverse relationshipbetween survivin and p16INK4a expression was observed (r=-0.459,P<0.01). 4. Survivin was highly expression in fiberobronchoscopicaspirates exfoliated cells of NSCLCs (78.2%),but not expression infiberobronchoscopic aspirates exfoliated cells of benign pulmonarydiseases; there was remarkably higher p16INK4a negative expression infiberobronchoscopic aspirates exfoliated cells of NSCLCs than in those ofbenign pulmonary diseases (58.5% vs 14.2%, P<0.01). 5. In situhybyidization and immunocytochemistry were used to detect mRNA andprotein expression of survivin and p16INK4a in fiberobronchoscopicaspirates exfoliated cells of NSCLCs. There was a good coincidence ratebetween the results of In situ hybyidization and its ofimmunocytochemistry(95.1%,92.4% ,respectively).The positive expressionof survivin mRNA and p16INK4a mRNA showed a marked relationshipwith its protein expression. 6.The combination of conventional cytologicalexamination and detection of survivin produced a sensitivity of82.7%,specificity of 100%,positive predictive value of 100%,negativepredictive value of 60%; by combination of conventional cytologicalexamination and detection of p16INK4a , sensitivity was 71.7%, specificitywas 92.8%, positive predictive value was 98%, negative predictive valuewas 27.5%; the combination of conventional cytological examination andmolecular biological detection of survivin gene and p16INK4a gene canincrease sensitivity to 91%, specificity to 95%, positive predictive value to96%, negative predictive value to 71%.Detection of apoptosis inhibitorgene ,tumor suppressor gene in fiberobronchoscopic aspirates exfoliatedcells can increase sensitivity and negative predictive value of conventionalcytological examination (P<0.05).Conclusion:Overexpression of survivin and negative expression ofp16INK4a in non-small cell lung carcinomas indicate survivin andp16INK4a paly an important role in the regulation of tumorigenesis anddevelopment in NSCLC through inhibiting cancer cell apoptosis andpromote proliferation. Survivin and p16INK4a may be biomarkersprognostic factors for NSCLC. By combination of conventional cytologicalexamination and molecular biological detection of survivin gene andp16INK4a gene can increase sensitivity and negative predictive value ofconventional cytological examination,it might help to increase thepositive rate of early diagnosis for NSCLC. Survivin and p16INK4a couldbe new diagnostic/therapeutic targetes in non-small cell lung carcinoma.