非小细胞肺癌组织中TTF-1和Ki67的表达及意义
摘要
背景
肺癌的发病率及死亡率均居恶性肿瘤的首位,非小细胞肺癌(NSCLC)约占80%左右。含铂类药物的两联方案是标准的治疗方案,但其有效率仅有20%-35%左右。随着对肺癌分子生物学研究的深入,人们认识到不同的肿瘤有不同的驱动基因和蛋白表达,为肿瘤的分子靶向治疗奠定了基础。
目的
检测甲状腺转录因子-1(TTF-1)、Ki-67在非小细胞肺癌组织中的表达,探讨其临床意义,以期为非小细胞肺癌患者的诊断、治疗和预后评估提供有价值的分子生物学指标。
方法
将郑州大学第二附属医院2007年1月至2010年12月经病理检查确诊的原发性肺非小细胞癌134例患者作为研究对象,采集病例相关的临床病理资料,免疫组织化学法检测的TTF-1、Ki-67表达,采用SPSS17.0统计软件包进行数据分析。
结果
1.肺腺癌组织中TTF-1蛋白表达高达80.9%(55/68),而鳞癌组织中其表达率仅为7.0%(53/57),两者之间存在显著性差异(P=0.001)；Ki-67蛋白表达在肺鳞癌、肺腺癌、肺腺鳞癌无显著性差异(P=0.063)。
2.TTF-1蛋白表达率在女性、细胞分化好、较小的肿瘤(最大径≤3cm)及I期、II期患者中较高(P<0.05)；Ki-67蛋白在有吸烟史、细胞分化差及有淋巴结转移的患者中有较高表达(P<0.05)。
3. Logistic回归分析显示：细胞分化程度、肿瘤大小及病理类型为TTF-1蛋白表达的影响因素(P<0.01)；Ki-67蛋白表达的影响因素为细胞分化程度和淋巴结转移情况(P<0.01)。
4.TTF-1的表达与Ki-67的表达无明显相关性(r=0.115,P=0.188)。
5.TTF-1阳性表达组患者生存率大于TTF-1阴性表达组,两组中位生存期分别为31个月及14个月,两组间有显著性差异(P=0.001)；Ki-67阳性表达组患者生存率小于Ki-67阴性表达组,两组中位生存期分别为18个月及26个月,两组间有显著性差异(P=0.014)。
6.cox回归分析显示：TTF-1、Ki-67,临床分期、肿瘤大小是影响非小细胞肺癌预后的独立因素(P<0.01)。
结论
1NSCLC中TTF-1的表达,可为不同类型肺癌的鉴别诊断提供有价值的指标。
2细胞分化越差,肿瘤越大,临床分期越晚,TTF-1表达阳性率越低,生存时间越短。提示TTF-1低表达肿瘤可能预示有较高的侵袭性及预后不良。
3Ki67表达越高可能预示肿瘤细胞的浸润、转移能力越强,生存时间较短。
4Ki-67、TTF-1可作为判断NSCLC的生物学行为及预后的参考指标。
Background
Lung cancer is first leading cause of the incidence and cancer-related death in the world. Non-small cell lung cancer (NSCLC) accounts for approximately80%of these cases. The standard treatment is two agents combination schemes including the platinum drugs, but its efficient is only20%～35%or so. Along with the recognation of its genotype, people realize that different tumor have different gene phenotypes, protein expression patterns and biology behavior.
Objectives
To study the expression alterations of Thyroid Transcription Factor1(TTF-1) and Ki-67in NSCLC, and explore their clinical significance for diagnosis, treatment and evaluation of prognosis of NSCLC.
Methods
One hundred and thirty four primary NSCLC tissue specimens and their related clinical pathology materials from the second affiliated hospital of Zhengzhou University between January2007and December2010were collected. The expressions of TTF-1and Ki67were detected by immunohistochemical staining. The data were analysised by statistical package SPSS17.0.
Results
1. TTF-1was expressed positively in [80.9%(55/68)] of lung adenocarcinoma, higher than that in squamous carcinoma[7.0%(4/57)],(P=0.001). There was no statistical significance for the expression of Ki67among pulmonary squamous carcinoma, adenocarcinoma and adenosquamouscarcinoma(P=0.063).
2. TTF-1was significantly upregulated (p<0.05) in patients of female, with high grade cellular differentiation, tumor size less than3cm and stage Ⅰ and Ⅱ. The expression of K-i67was related to smoking, the grade of cellular differentiation and the metastasis of lymph node(p<0.05).
3. Logistic regression analysis showed that histological classification, cell differentiation and size of primary tumor were the factors related to expression of TTF-1(p<0.01); the factors related to expression of K-i67were the grade of cellular differentiation and the metastasis of lymph node (P<0.01).
4. There was no significant relevance between the expression of TTF-1and Ki-67(r=0.115,P=0.188).
5. Statistical analysis showed that the survival time of NSCLS with TTF-1positive was superior to that with TTF-1negativ e(p=0.001). Both of median survival time was31and14months, and the survival time of NSCLS with Ki-67positive were shorter than that with Ki67negative(p=0.014). Both of median survival time were18and26months,survival curves were statistically significant difference.
6. TTF-1, Ki-67, the size of primary tumor and TNM stage were independent factors affecting the NSCLC (P<0.01).
Conclusions
1. The expression of TTF-1is high in pulmonary adenocarcinoma, which could be a valuable index in the diagnosis of pulmonary adenocarcinoma.
2. The poor cell differentiation, bigger tumor volume, higher TNM stage and lower positive expression rate of TTF-1, are negative factors for survival time in NSCLC. The clinical course is more aggressive and the outcome is worse for those with lower expression of TTF-1.
3. The higher expression of Ki67may be indicator of the malignant transformation of lung cell, infiltration of tumor, metastasis and shorter survival time.
4. It's possible that TTF-1and Ki-67could provide valuable reference for judging lung cancer biology behavior and predict the prognosis of patients with NSCLC.
肺癌的发病率及死亡率均居恶性肿瘤的首位,非小细胞肺癌(NSCLC)约占80%左右。含铂类药物的两联方案是标准的治疗方案,但其有效率仅有20%-35%左右。随着对肺癌分子生物学研究的深入,人们认识到不同的肿瘤有不同的驱动基因和蛋白表达,为肿瘤的分子靶向治疗奠定了基础。
目的
检测甲状腺转录因子-1(TTF-1)、Ki-67在非小细胞肺癌组织中的表达,探讨其临床意义,以期为非小细胞肺癌患者的诊断、治疗和预后评估提供有价值的分子生物学指标。
方法
将郑州大学第二附属医院2007年1月至2010年12月经病理检查确诊的原发性肺非小细胞癌134例患者作为研究对象,采集病例相关的临床病理资料,免疫组织化学法检测的TTF-1、Ki-67表达,采用SPSS17.0统计软件包进行数据分析。
结果
1.肺腺癌组织中TTF-1蛋白表达高达80.9%(55/68),而鳞癌组织中其表达率仅为7.0%(53/57),两者之间存在显著性差异(P=0.001)；Ki-67蛋白表达在肺鳞癌、肺腺癌、肺腺鳞癌无显著性差异(P=0.063)。
2.TTF-1蛋白表达率在女性、细胞分化好、较小的肿瘤(最大径≤3cm)及I期、II期患者中较高(P<0.05)；Ki-67蛋白在有吸烟史、细胞分化差及有淋巴结转移的患者中有较高表达(P<0.05)。
3. Logistic回归分析显示：细胞分化程度、肿瘤大小及病理类型为TTF-1蛋白表达的影响因素(P<0.01)；Ki-67蛋白表达的影响因素为细胞分化程度和淋巴结转移情况(P<0.01)。
4.TTF-1的表达与Ki-67的表达无明显相关性(r=0.115,P=0.188)。
5.TTF-1阳性表达组患者生存率大于TTF-1阴性表达组,两组中位生存期分别为31个月及14个月,两组间有显著性差异(P=0.001)；Ki-67阳性表达组患者生存率小于Ki-67阴性表达组,两组中位生存期分别为18个月及26个月,两组间有显著性差异(P=0.014)。
6.cox回归分析显示：TTF-1、Ki-67,临床分期、肿瘤大小是影响非小细胞肺癌预后的独立因素(P<0.01)。
结论
1NSCLC中TTF-1的表达,可为不同类型肺癌的鉴别诊断提供有价值的指标。
2细胞分化越差,肿瘤越大,临床分期越晚,TTF-1表达阳性率越低,生存时间越短。提示TTF-1低表达肿瘤可能预示有较高的侵袭性及预后不良。
3Ki67表达越高可能预示肿瘤细胞的浸润、转移能力越强,生存时间较短。
4Ki-67、TTF-1可作为判断NSCLC的生物学行为及预后的参考指标。
Background
Lung cancer is first leading cause of the incidence and cancer-related death in the world. Non-small cell lung cancer (NSCLC) accounts for approximately80%of these cases. The standard treatment is two agents combination schemes including the platinum drugs, but its efficient is only20%～35%or so. Along with the recognation of its genotype, people realize that different tumor have different gene phenotypes, protein expression patterns and biology behavior.
Objectives
To study the expression alterations of Thyroid Transcription Factor1(TTF-1) and Ki-67in NSCLC, and explore their clinical significance for diagnosis, treatment and evaluation of prognosis of NSCLC.
Methods
One hundred and thirty four primary NSCLC tissue specimens and their related clinical pathology materials from the second affiliated hospital of Zhengzhou University between January2007and December2010were collected. The expressions of TTF-1and Ki67were detected by immunohistochemical staining. The data were analysised by statistical package SPSS17.0.
Results
1. TTF-1was expressed positively in [80.9%(55/68)] of lung adenocarcinoma, higher than that in squamous carcinoma[7.0%(4/57)],(P=0.001). There was no statistical significance for the expression of Ki67among pulmonary squamous carcinoma, adenocarcinoma and adenosquamouscarcinoma(P=0.063).
2. TTF-1was significantly upregulated (p<0.05) in patients of female, with high grade cellular differentiation, tumor size less than3cm and stage Ⅰ and Ⅱ. The expression of K-i67was related to smoking, the grade of cellular differentiation and the metastasis of lymph node(p<0.05).
3. Logistic regression analysis showed that histological classification, cell differentiation and size of primary tumor were the factors related to expression of TTF-1(p<0.01); the factors related to expression of K-i67were the grade of cellular differentiation and the metastasis of lymph node (P<0.01).
4. There was no significant relevance between the expression of TTF-1and Ki-67(r=0.115,P=0.188).
5. Statistical analysis showed that the survival time of NSCLS with TTF-1positive was superior to that with TTF-1negativ e(p=0.001). Both of median survival time was31and14months, and the survival time of NSCLS with Ki-67positive were shorter than that with Ki67negative(p=0.014). Both of median survival time were18and26months,survival curves were statistically significant difference.
6. TTF-1, Ki-67, the size of primary tumor and TNM stage were independent factors affecting the NSCLC (P<0.01).
Conclusions
1. The expression of TTF-1is high in pulmonary adenocarcinoma, which could be a valuable index in the diagnosis of pulmonary adenocarcinoma.
2. The poor cell differentiation, bigger tumor volume, higher TNM stage and lower positive expression rate of TTF-1, are negative factors for survival time in NSCLC. The clinical course is more aggressive and the outcome is worse for those with lower expression of TTF-1.
3. The higher expression of Ki67may be indicator of the malignant transformation of lung cell, infiltration of tumor, metastasis and shorter survival time.
4. It's possible that TTF-1and Ki-67could provide valuable reference for judging lung cancer biology behavior and predict the prognosis of patients with NSCLC.
引文
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