南方医科大学学报

南方医科大学学报 ›› 2006, Vol. 26 ›› Issue (10): 1423-1426.

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组织芯片检测甲状腺转录因子-1蛋白在肺癌细胞核中表达的定量研究

白晓燕； 申洪；   

  1. 南方医科大学病理学教研室； 南方医科大学病理学教研室 广东广州510515； 广东广州510515；
  • 出版日期:2006-10-20 发布日期:2006-10-20
  • 基金资助:
    国家自然科学基金(30271462);广东省科技攻关计划(2KM04501S);广州市科技攻关重点项目(2003Z2-E0061、E0062)~~

Quantitative study of thyroid transcription factor-1 protein expression in lung carcinoma cell nucleus by tissue microarray

BAI Xiao-yan, SHEN Hong Department of Pathology, Southern Medical University, Guangzhou 510515, China   

  1. 南方医科大学病理学教研室； 南方医科大学病理学教研室 广东广州510515； 广东广州510515；
  • Online:2006-10-20 Published:2006-10-20

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摘要： 目的揭示甲状腺转录因子-1(TTF-1)蛋白在正常成人肺泡Ⅱ型上皮细胞、人胚胎肺泡上皮细胞、肺癌原发灶及淋巴结转移灶中的表达特点及规律。方法用组织微阵列技术构建包含20例正常成人肺组织、15例胚胎肺组织、100例肺癌原发灶及其相应的55例淋巴结转移灶的765点阵的石蜡组织芯片。用免疫组化SP法检测该芯片中TTF-1蛋白的表达。用LeicaQ500MC图像分析系统定量测试组织芯片上TTF-1蛋白的表达强度。结果胚胎肺泡上皮细胞核TTF-1阳性单位(PU)值小于正常成人肺泡Ⅱ型上皮细胞核TTF-1的PU值(P<0.001);不同类型肺癌癌细胞核TTF-1的PU值均小于胚胎肺泡上皮细胞和正常成人肺泡Ⅱ型上皮细胞核TTF-1的PU值(P<0.001);肺腺癌和肺小细胞癌癌细胞核TTF-1的PU值均大于肺鳞癌和肺大细胞癌癌细胞核TTF-1的PU值(P<0.001);肺鳞癌癌细胞核TTF-1的PU值大于肺大细胞癌癌细胞核TTF-1的PU值(P<0.001)。肺的腺癌、鳞癌和大细胞癌淋巴结转移灶中癌细胞核TTF-1的PU值均大于其癌原发灶癌细胞核TTF-1的PU值(P<0.001,P<0.001,P<0.05);肺小细胞癌淋巴结转移灶癌细胞核TTF-1的PU值与其原发灶癌细胞核TTF-1的PU值基本相同(P>0.05)。有淋巴结转移的肺癌原发灶癌细胞核TTF-1的PU值大于无淋巴结转移的肺癌原发灶癌细胞核TTF-1的PU值(P<0.001);癌细胞胞核TTF-1的PU值与肺癌大体类型、分化程度和患者性别无关(P>0.05);TNMⅡ-Ⅳ期癌细胞胞核TTF-1的PU值大于Ⅰ期(P<0.001)。结论TTF-1的表达量在正常成人肺泡Ⅱ型上皮细胞、胚胎肺泡上皮细胞和肺癌细胞核中的表达具有差异性并依次减少;肺癌细胞核TTF-1的表达具有癌组织类型差异性,腺癌和小细胞癌相对较高,鳞癌和大细胞癌极少;TTF-1胞核高表达的肺癌易发生转移,TTF-1胞核高表达的肺的腺癌、鳞癌和大细胞癌癌细胞为具有明显转移能力的肺癌细胞的重要标志之一。

Abstract: Objective To investigate thyroid transcription factor-1 (TTF-1) expression in normal human adult type Ⅱ alveolar epithelial cells, embryonic pneumocytes, lung carcinoma cells and lymph node metastases of lung cancer. Methods Lung carcinoma tissue microarray was constructed containing 765 cores of 20 normal adult lung tissues, 15 embryonic lung tissues, 100 lung carcinomas and 55 corresponding lymph node metastases. TTF-1 protein expression on the microarray was detected by immunohistochemical SP method using TTF-1 monoclonal antibody and assessed quantitatively with Leica Q500MC image analysis system. Results The number TTF-1 positive units (PU) was smaller in the nuclei of embryonic pneumocytes than in those of normal adult type Ⅱ alveolar epithelial cells (P<0.001). The nuclei of lung carcinoma cells had smaller TTF-1 PU than normal adult type Ⅱ alveolar epithelial cells and embryonic pneumocyte nuclei (P<0.001). The lung adenocarcinoma and small cell lung carcinoma cell nuclei had greater TTF-1 PU than squamous cell carcinoma and large cell lung carcinoma cell nuclei (P<0.001). TTF-1 PU was greater in squamous cell carcinoma cell nuclei than in large cell lung carcinoma cell nuclei (P<0.001). In lung adenocarcinoma, squamous cell lung carcinoma and large cell lung carcinoma, TTF-1 PU was greater in the cancerous cell nuclei of lymph node metastases than in the corresponding primary carcinoma cell nuclei (P<0.001, P<0.001, and P<0.05, respectively). In small cell lung carcinoma, TTF-1 PU of the cancerous cell nuclei of lymph node metastases was similar to that of primary carcinomas (P>0.05). TTF-1 PU was greater in lung carcinoma with lymph node metastases than in those withouts metastalsis (P<0.001). TTF-1 PU of the cell nuclei was not associated with the tumor growth pattern, differentiation and patients’ gender (P>0.05), but was greater in TNM stage Ⅱ-Ⅳ than in stage Ⅰ (P<0.001). Conclusions The amount of TTF-1 in the cell nuclei decreases in the order of normal adult type Ⅱ alveolar epithelial cells, embryonic pneumocytes and lung carcinoma cells. TTF-1 expression is higher in adenocarcinoma and small cell carcinoma and lower in squamous carcinoma and large cell carcinoma. Stronger TTF-1 expression is associated with greater likeliness of lung carcinoma metastatie, and can be an important hallmark for metastasis potential of lung adenocarcinoma, squamous cell carcinoma and large cell carcinoma.

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