pT_1期肺腺癌组织TK1与PCNA和Ki-67表达临床意义对比分析

Comparative study:the significance of TK1,PCNA and Ki-67 expression in pT_1 adenocarcinoma of lung tissues

目的:对比研究增殖指标胸苷激酶1(cytosolic thymidine kinas 1,TK1)和增殖细胞核抗原(proliferation cell nuclear antigen,PCNA)与Ki-67在病理分期T1(pT1)期肺腺癌组织中表达及其临床意义。方法:选取南京军区南京总医院1997-02-01-2007-12-31手术治疗并具有完整病理资料和随访结果的pT1期肺腺癌患者80例,应用免疫组织化学EnVision法检测80例肺腺癌以及20例正常肺组织中TK1、Ki-67及PCNA的表达,对比分析3项标志表达与肺腺癌临床病理特征和预后的相关性。结果:pT1期肺腺癌与正常肺组织中TK1表达率-为15.0%和95.0%,+为33.8%和5.0%,++为38.8%和0,+++为12.5%和0,差异有统计学意义,P<0.001;Ki-67表达率-为46.3%和85.0%,+为40.0%和15.0%,++为8.7%和0,+++为5.0%和0,差异有统计学意义,P=0.002;PCNA表达率与正常肺组织差异无统计学意义,P=0.507。TK1表达与淋巴结转移(P=0.009)、临床病理分期(P=0.004)及肿瘤浸润程度(P<0.001)相关,Ki-67和PCNA表达与上述临床病理特征均无相关性。TK1不同表达组别的5年生存率除-(91.7%)与+(81.1%)组之间以及++(38.7%)与+++(50.0%)组之间差异无统计学意义外,其余各表达组别间差异均有统计学意义,而不同PCNA及Ki-67表达组别间的预后差异无统计学意义。Cox模型多因素预后分析显示,TK1表达、淋巴结转移及临床病理分期是独立预后因素。结论:pT1期肺腺癌中,TK1是一项比Ki-67及PCNA更可靠的增殖指标,可作为评估这类肺腺癌侵袭性及预后的参考指标。

OBJECTIVE： To comparatively study the significance of expression of TK1,PCNA and Ki-67 in patho- logical-T1 （pT1） adenocarcinoma of lung. METHODS： Eighty cases of surgically resected pT1 lung adenocarcinoma and 20 eases of normal lung tissues,from February 1 1997 to December 31 2007 in Nanjing General Hospital of Nanjing Com- mand, were sampled to detect the expression of TK1,Ki-67 and PCNA by immunohistochemistry （EnVision method）. The correlation between expression of three markers and clinicopathologic characteristics and patient survival were analyzed comparatively. RESULTS：The negative -- and the weak ＋ ,moderately ＋＋ and strong ＋＋＋ positive stains of TK1 were exhibited in 15.0% ,33.8% ,38.8% and 12.5% of pT1 adenocarcinomas of lungr,normal lung tissue were 95.0% ,5.0%, 0 and 0, it showed statistically significant differences, P〈0.001 ; Ki-67 exhibited in 46.3 %, 40.0 %, 8.7 % and 5.0 % cases of tumor, and normal lung tissue were 85.0%, 15.0 %, 0 and 0, it showed statistically significant differences, P = 0. 002;it showed no statistically significant difference between pTa adenocarcinomas of lungr and normal lung tissue of PCNA. There were significant relevances between TK1 LI and lymph node involvement （P = 0. 009）, clinicopathologic stage （P =0. 004） and tumor invasion degree （P〈0. 001） ,which was not found for Ki-67 and PCNA. According to the different ex- pression level of TKl,the statistically significant difference of the 5-year survival was found between any two groups,ex- cept the groups between -（91.7%） and ＋ （81.1%）,and ＋＋ （38.7%） and ＋＋＋ （50%）. No relationship was found between patient survival and expression of PCNA or Ki-67. Multivariate analysis revealed that the expression of TK1, lymph node involvement and the clinicopathologic stage were independent prognostic factors. CONCLUSION.. Compared with Ki-67 and PCNA,TK1 is a more reliable proliferation index in pT1 adenocarcinoma of lung, which can evaluate the in- vasion and the prognosis of tumor.