非小细胞肺癌患者肿瘤组织胸苷酸合成酶表达的意义

The significance of thymidylate synthase expression in non-small cell lung cancer tumor tissue

目的：探讨非小细胞肺癌患者肿瘤组织中胸苷酸合成酶（ TS）的表达水平与年龄及其他临床病理特征之间的关系。方法回顾分析2008年3月至2009年10月在首都医科大学附属北京胸科医院肿瘤科住院，且经外科手术确诊的302例非小细胞肺癌（ NSCLC）患者的临床资料及石蜡包埋的肿瘤组织标本。将患者按年龄分为3组：≤45岁组，46～69岁组，≥70岁组；用免疫组化（ IHC）半定量法测定瘤组织中TS的表达，IHC得分范围0～9分，按IHC得分分为低表达（0～3分）和高表达（＞3分）。采用SPSS 17．0软件对资料进行统计分析，不同组别TS表达率的显著性检验采用χ2检验；患者年龄和肿瘤组织分化程度符合正态分布，其与IHC得分的相关性采用Pearson相关分析法进行分析。结果302例患者中鳞癌140（46．4％）例，非鳞癌162（53．6％）例。 TS高表达在鳞癌32．1％（45／140），非鳞癌29．0％（47／162）中，差异无统计学意义（χ2＝0．35， P＝0．556）。不同年龄组患者肿瘤组织TS高表达率分别为：≤45岁组45．2％（14／31）、46～69岁组31．7％（70／221）和≥70岁组16．0％（8／50），差异有统计学意义（χ2＝8．52， P ＝0．016）。287例NSCLC患者病理有分化程度，低分化和中高分化肿瘤组织TS高表达率分别为37．8％（37／98）和25．4％（48／189），差异有统计学意义（χ2＝4．73， P ＝0．030）。相关性分析显示年龄与IHC得分呈负相关（ r ＝－0．15， P ＝0．010）；分化程度与IHC得分无关（ r ＝－0．11， P ＝0．057）。 NSCLC患者不同病理类型性别、吸烟指数、肿瘤大小、TNM分期和有无淋巴结转移间TS蛋白表达水平，均差异无统计学意义（χ2＝0．35，0．85，0．41，0．01，0．16，0．67；P＞0．05）。结论 NSCLC瘤组织表达TS水平高低与年龄和肿瘤分化程度相关；不同年龄组患者和不同分化程度的肿瘤组织TS表达的水平有差异，仅年龄与TS的表达呈负相关。

Objective To explore the relationship among the thymidylate synthase （ TS） level,age and different clinicopathologic features in human non？small cell lung cancer（NSCLC） tumor tissue.Methods The clinical data and operative specimens of 302 NSCLC patients were collected in Oncology of Beijing Chest Hospital from March 2008 to October 2009. TS protein expression was evaluated by semi？quantitative immunohistochemistry （IHC） in formalin？fixed paraffin？embedded （FFPE） specimens.Patients were divided into three groups：≤45 years old group,the 46~69 age group,≥70 years old group.IHC scores range was 0~9 points.Furthermore,according to the IHC score,patients were divided into two groups：low group （0~3 points） and high group（〉3 points）.TS expression rates in different groups were analyzed byχ2 test and the correlation analysis was conducted by Pearson correlation analysis. Results There were 140 （ 46. 4%） squamous cell carcinoma and 162（53.6%） non？squamous cell carcinoma patients in the total 302 cases.The＆amp;nbsp;rate of TS high expression in squamous cell carcinoma was 32. 1% （ 45/140） while in non？squamous cell carcinoma was 29.0% （47/162） respectively,no significant difference was observed（ χ2=0.35, P =0.556）. TS high expression rates in different age groups were 45.2% （14/31）,31.7% （70/221） and 16.0% （8/50） respectively,and the difference was statistically significant （ χ2=8.52, P =0.016） . Two hundred and eighty？seven NSCLC patients had pathologic differentiation, TS high expression rates in poorly differentiated and well？differentiated tumor tissue were 37.8%（37/98） and 25.4%（48/189） respectively,the difference was statistically obvious （ χ2=4.73, P =0.030）.Correlation analysis showed that age was negatively correlated with the IHC scores（ r =-0.15, P =0.010）;IHC scores had no correlation with the degree of differentiation （ r =-0.11, P =0.057）.No significant difference was found in TS expression among pathological type,sex, smoking index,tumor size,TNM stage and lymph node metastasis（ χ2=0.35,0.85,0.41,0.01,0.16,0.16;P〉0.05）.Conclusion TS expression in NSCLC tumor′s tissue is relative to age as well as the degree of tumor differentiation,but it is only negatively correlated with age.