pT1期肺腺癌组织TK1与PCNA和Ki-67表达临床意义对比分析

目的：对比研究增殖指标胸苷激酶1（eytosolic thymidine kinas1，TK1）和增殖细胞核抗原（proliferation cellnu—clear 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En Vision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．O％，＋为40．0％和15．0％，＋＋为8．7％和0，＋＋＋为5．O％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。

Comparative study,the significance of TK1, PCNA and Ki-67 expression in pT1 adenocarcinoma of lung tissues

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 th