摘要
背景与目的作为肿瘤抑制因子,早幼粒细胞白血病(PML)蛋白同P53和P16INK4A在肺癌中的表达关系、以及PML与肺癌临床预后关系不明。本研究旨在揭示三者在肺癌中的表达关系,以及与临床和预后之间的联系。方法构建包含144例肺癌,12例肺良性肿瘤和正常组织的组织芯片,利用SP免疫组化检测蛋白表达。阳性率比较采用列联表法。Kaplan-Meier法用来估计生存差异,组间比较应用Logrank检验。Cox风险比例模型用来进行单因素和多因素生存分析。结果PML在121例非小细胞肺癌(NSCLC)和23例小细胞肺癌(SCLC)细胞浆的表达率分别为14.0%和39.1%(P=0.010),在细胞核的表达率分别为31.4%和8.7%(P=0.026);PML阳性SCLC患者的5年生存率50%,显著高于阴性者的23%(P=0.047);多因素分析显示PML表达是SCLC预后的保护因素。P53在肺癌的阳性率为33.3%,在肺良性肿瘤和正常组织无表达(P=0.038);P16INK4A在肺癌(28.5%)尤其在分化低和未分化肺癌(36.5%)、SCLC(69.6%)中高表达。肺癌中PML细胞核表达与P16INK4A表达呈负相关,P53与P16INK4A在肺癌和腺癌的表达呈正相关,PML与P53在鳞癌的表达呈负相关。结论作为肿瘤抑制因子,PML在鳞癌中与P53基因突变存在联系,并可能与P16INK4A共同成为SCLC的标记物;肺癌中高表达的P16INK4A蛋白可能是基因突变产物,与突变型P53蛋白存在相关性。
Background and objective The promyelocytic leukaemia (PML) protein has been implicated in control of key tumor-suppressive pathways. However, its role in pathogenesis of lung cancer is still unclear. The objective of this study is to assess expression and clinical significance of PML, P53 and P16INK4A in lung cancer, as well as the relation of these factors. Methods The tissue microarrays were created with samples from lung cancers (n=148), pulmonary benign lung tumors (n=5) and normal lung tissues (n=7), and protein expression was analyzed by immunohistochemical staining. The association between protein expression and clinical parameters was evaluated by using Crosstabs method. The Kaplan-Meier method was used to estimate survival. Cox proportional hazards model was used for univariate and multivariate analysis. Results There was at least triplicate 0.6-mm cores per sample, 4 cases of lung cancer were excluded for lacking of enough tissue. PML was found in the cytoplasm of 14.0% cases of NSCLC and of 39.1% SCLC (P=0.010), and in the nuclei of 31.4% NSCLC and 8.7% SCLC respectively (P=0.026). PML protein was present in 9 patients with SCLC and absent in 14 cases, 5-year cumulative survival rate of the patients was 50% and 23% respectively (Log-rank test, P=0.047). Lacking of PML protein and senior pathologic T-stage were two hazardous factors that influenced prognosis of SCLC. P53 expression was found in 33.3% lung cancer, and absent in benign tumors and normal tissues of the lung (P=0.038). P16INK4A expression was abolished in normal lung tissue, however, increased in lung cancer (28.5%), and especially in lung cancer with non- or poor differentiation (36.5%) and in SCLC (69.6%). There was inverse correlation between PML expression in the nuclei and P16INK4A expression, positive correlation between P53 and P16INK4A expressions in lung cancers. PML was negatively correlated with P53 in squamous cell carcinoma. Conclusion As an important suppressor of tumor, PML is related with P53 mutation in squamous cell carcinoma. Increased P16INK4A protein in lung cancer may be the results of gene mutation, and be related with mutant P53 protein.
出处
《中国肺癌杂志》
CAS
2007年第3期176-182,共7页
Chinese Journal of Lung Cancer
