【作者】 郑宏伟；

【导师】 王新允；

【作者基本信息】 天津医科大学 ， 病理与病理生理学， 2003， 硕士

【摘要】 目的：通过检测COX-2及相关指标在人类肺癌组织中的表达及其与临床病理学参数间的关系，探讨COX-2在影响肺癌组织细胞凋亡、肿瘤血管形成、侵袭及转移性等方面的作用及其分子机制，拟为临床病理诊断和针对肺癌的新药开发与治疗提供一定的理论依据。 方法：实验组包括101例石蜡包埋的肺癌标本，对照组包括7例正常肺组织。采用免疫组织化学SP法检测了COX-2、K-ras、Mcl-1和CD44蛋白的表达水平，并用Ⅷ因子标记肺癌血管，利用CMIAS2000型多功能真彩病理图象分析系统定量检测各指标在不同病例中蛋白表达的积分光密度(IOD)和平均光密度(AOD)，并计算微血管密度(MVD)。应用SPSS11.0版软件包进行数据处理。 结果： 1．COX-2蛋白在实验组101例肺癌组织中的阳性表达率为28.7％，较对照组(0.0％)升高，但差异不显著(p＞0.05)，在73例NSCLC组中的阳性表达率为39.7％，较对照组(0.0％)升高，且具有显著性差异(p=0.045)。 2．COX-2在各组织学类型肺癌中表达的阳性率和表达水平均不同，腺癌＞鳞癌＞大细胞癌，小细胞癌未见表达，且具有显著性差异(p=0.000，p=0.000)。不同肉眼类型肺癌的COX-2表达水平具有显著性差异(p=0.005)，周围型肺癌高于中央型肺癌。不同年龄、性别、组织学分级、临床分期、有无淋巴结转移和有无吸烟史组间无显著性差异，但合并分期之后，Ⅰ+Ⅱ期和Ⅲ+Ⅳ期之间的差异具有统计学意义(p=0.048)。 3．K-ras在肺癌组中阳性率44.6％，较对照组升高，具有显著性差异(p=0.040)，在NSCLC组中阳性率60.3％，较对照组升高，且具有显著性差异(p=0.003)。 4．K-ras蛋白在不同的组织学类型的肺癌中表达水平不同，大细胞癌＞腺癌＞鳞天门户压早早大掌刁卜亡石冷丈戈mr一2在人未肺减杏中月犯马廿夕J七扮掌龙名及J膝j必子机倒的书九户臼贾讨 癌>小细胞癌，各组间具有显著性差异(p=0.000)，不同肉眼类型组间具有 显著性差异(p=0 005)，周围型肺癌高于中央型肺癌组，但K一ras蛋白的表达 水平与其它病理学参数无关。5.Md一1在肺癌组中阳性率25.7%，较对照组升高，但无显著性差异(p=0.192)， 在NscLC组中阳性率35.6%，较对照组升高，亦无显著性差异(p=0.090)。6.Mcl一l蛋白的表达水平在不同的组织学类型的肺癌中的表达水平不同，腺癌 >大细胞癌>鳞癌，小细胞癌未见表达，各组间具有显著性差异(p=0.000)， 但Mcl一l蛋白的表达水平与其它病理学参数无关。7.CD44在肺癌组中阳性率347%，较对照组升高，但无显著性差异(p=0.094)， 在NSCLC组中阳性率479%，较对照组升高，具有显著性差异(p二0.016)。8.肺癌中CD44蛋白的表达在有无淋巴结转移组间有显著性差异(p=0.014)， 淋巴结转移阳性组明显高于淋巴结转移阴性组。不同的组织学类型的肺癌中 的表达水平不同，大细胞癌>腺癌>鳞癌，小细胞癌未见表达，各组间具有 显著性差异(p=。.000)，但cD44蛋白的表达水平与其它病理学参数无关。9.肺癌组织中的MvD值明显高于正常对照组织，具有显著性差异(p=0.001)， NSCLC组织中的MVD值明显高于正常对照组织，具有显著性差异 (P=0 .001)。10.MVD值在不同组织学分级的肺癌中不同，随分化程度的增高MVD值降 低，各组间具有显著性差异(p=0.034)，但MVD值与其它病理学参数无关。1 1.肺癌中COX一2与Mel一l、K一ras、CD44的表达呈明显正相关。K一ras与 COX一2、Mel一l、CD44的表达呈明显正相关。Mel一l与CD44的表达不相关。12.在101例肺癌组织中，COX一2和K一ras阳性组中MVD值高于COX一2阴性 组(P=O .047，p=0 .032)有显著性差异，且MVD值与Cox一2和K一ras蛋白 的表达水平具有正相关关系。CD44阳性组中M万D值高于CD44阴性组，并 具有显著性差异(p=0.044)，但MvD值与CD44蛋白的表达水平不相关。 Mcl一1阳性组与MCL一1阴性组之间MVD值无显著性差异，且MvD值与一3一天门户压才毕夕气攀习卜亡刁月充J七及片一2在.人刀盼盛杏中月犯艾的总扮攀葱火及J〔j必子执蒯的右九户脚砚讨 Mcl一1蛋白的表达水平不相关。结论:1.肺癌中COX一2蛋白表达升高且在各组织学类型肺癌中的表达不同，腺癌 >鳞癌>大细胞癌，小细胞癌未见表达，提示COX一2参与了人类肺癌的形 成，并在不同组织学类型肺癌的发生、发展中发挥不同作用，不同组织学类 型的肺癌的形成机制有所区别，因此它们会具有不同的生物学行为，需要制 定有针对性的治疗方案。COX一2在腺癌中表达最高，可能是与腺上皮来源肿 瘤的生物学特点有关，也可能是COX一2参与了肺癌细胞的分化，此机制有 待于更深入地研究证实。2.肺癌中COX一2蛋白在不同肉眼类型组的表达有差异，周围型肺癌中 COX一2的表达水平高于中央型肺癌组，由于中央型肺癌多为鳞癌，周围型 肺癌多为腺癌，而我们的结果也证实肺腺癌中COX一2的表达高于鳞癌，两 结果彼此相符，因此从肉眼类型角度也反映了不同类型肺癌中COX一2的作 用不同，为不同类型肺癌的临床诊断和将COX一2选择性抑制剂更多还原

【Abstract】 Objective: Overexpression of cyclooxygenase-2 is seen in high percentage of human rumors We intended to investigate the expression cyclooxygenase-2 and K-ras ,Mcl-l and CD44 in lung cancer tissue and their interaction with clinical pathological characteristics and to determine the effect of cyclooxygenase-2 in the processing of carcinogenesis , apoptosis ,angiogenesis , invasiveness and metastasis of lung cancer Another purpose of this study was to put our results into the practice of clinical diagnosis and therapyMaterial and Method: We examined COX-2 , K-ras, Mcl-1 and CD44 protein expression in lung cancer tissue and normal lung tissue using an immunohistochemical staining technique. Included in the current study were 101 lung cancer samples and 7 nomal lung samples as control Microvessel was stained by anti-factorVDl antibody to analyse microvessel density All quantitative data were collected by image analysis system and processed by SPSS Version 11.0 Analysis software Result:1 . COX-2 protein was detectable in 28 7% of all 101 lang cancer tissues, which was higher than the group of control, but the difference was not significant The expression of COX-2 in 73 NSCLC tissues was 39.7% ,which was significantly-higher than the group of control (p=0045)2. The expressions of COX-2 in different histological types of lung cancer were various, and the difference were significant (p=0 000) The expression levels of peripheral type of lung cancer was significently higher than central type of lung cancer ( p=0 005 ) But no significant difference were detected between expressions of different sexes, ages, different histological grades , with lymph node metastasis or not , different clinical stages, had smoking history or not. But if the clinical stages were conbined into two that were group I + II and III+IV, the expression level of the last group was significantly higher than the former group (p=0.05) .3. K-ras protein was detectable in 44 6% of all 101 lang cancer tissues, which was higher than the group of control, and the difference was significant (p=0.040) . The expression of K-ras in 73 NSCLC tissues is 60.3 % ,which was significantly higher than the group of control (p=0 003)4. The expressions of K-ras protein in different histological types of lung cancer were various, and the difference were significant (p=0 000) But no significant difference were detected between the expressions of different sexes, ages, different histological grades , gross types, different clinical stages , with lymph node metastasis or not ,had smoking history or not5. Mcl-1 protein was detectable in 25.1% of all 101 lang cancer tissues, which was higher than the group of control, but the difference was not significant. The expression of Mcl-1 in 73 NSCLC tissues was 35.6%, which was higher than the group of control, but the difference was not significant, too.6. The expressions of Mcl-1 protein in different histological types of lung cancer were various, and the difference were significant (p = 0.000) But no significant difference were detected between the expressions of different sexes, ages, different histological grades, gross types, different clinical stages , with lymph node metastasis or not ,had smoking history or not7. CD44 protein was detectable in 34.7% of all 101 lang cancer tissues, which was higher than the group of control, but the difference was not significant. The expression of CD44 in 73 NSCLC tissues was 47.9% ,which was significantly higher than the group of control (p=0 016)8. The expressions of CD44 in tumors with lymph node metastasis were significantly higher than those without lymph node metastasis (p=0.014) . The expressions of CD44 protein in different histological types of lung cancer werevarious, and the difference were significant (p=0000) . But no significant difference were detected between the expressions of different sexes, ages, different histological grades, gross types, different clinical stages, had smoking history or not9. In lu更多还原