bFGF、EGFR与肺癌血管生成和转移的关系及血管在体成像分析
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摘要
目的：探讨bFGF、EGFR与非小细胞肺癌血管生成和转移的关系，并对荷瘤鼠肺癌血管在体成像分析，以寻求可靠的生物学指标及有效的血管观测方法，为肺癌的诊断及治疗提供理论基础和实验依据。
方法：用免疫组化SP法检测62例非小细胞肺癌和10例良性病变肺组织中bFGF、EGFR和CD34的表达，计数肿瘤MVD，并用原位杂交法检测肺癌组织中bFGF mRNA表达。建立荷瘤鼠肺癌移植瘤模型，利用激光共聚焦扫描显微镜对肿瘤血管连续断层扫描，比较实验组与对照组肿瘤血管的差异。
结果：bFGF、EGFR表达及MVD计数与非小细胞肺癌的分级、TNM分期及淋巴结转移呈正相关，在Ⅲ级高于Ⅰ～Ⅱ级、TNM分期的Ⅲ～Ⅳ期高于Ⅰ～Ⅱ期，有淋巴结转移组高于无淋巴结转移组，差异具有统计学意义(P＜0.05)。bFGF+/EGFR+的NSCLC，其MVD明显高于bFGF-/EGFR-组的MVD(P＜0.05)。荷瘤鼠肺癌血管在体扫描成像结果显示，实验组肿瘤血管较对照组粗大，血管密度增高，差异具有统计学意义(P＜0.05)。
结论：bFGF、EGFR高表达与NSCLC的分化程度、临床TNM分期、血管生成及淋巴结转移关系密切，联合检测bFGF、EGFR表达及MVD计数有助于评价NSCLC的生物学行为及预后。激光共聚焦扫描显微镜能直观、动态地反映肿瘤血管的走行及空间结构关系，为活体肿瘤血管的研究提供新的手段。
Purpose The purpose of this research was to explore the relationship of basic fibroblast growth factor (bFGF) and epidermal growth factor receptor (EGFR) with angiogenesis and lymph node metastasis of non-small cell lung cancer (NSCLC), and to analyze the blood vessel imagings of lung cancer transplanted BALB/c mice in vivo.
Methods The expression of bFGF, EGFR and CD34 was examined by immunohistochemical technique in 62 NSCLC and 10 benign lung lesions. In situ hybridization was used for further detecting of bFGF mRNA expression. In addition, the animal model of lung cancer transplanting BALB/c mice was established, and laser scanning confocal microscopy (LSCM) was used to scan continually the superficial vascular system of lung cancer in BALB/c mice to distinguish the difference between the experimental and the control groups in vivo.
Result The level of bFGF, EGFR protein expression and the microvessel density (MVD) of tumor tissues in differentiated grading III were remarkably higher than in differentiated grading I~II, and remarkably higher in III-IV stage than in I~II stage, and significantly higher in lymph node metastasis group than in non-metastasis group (P<0.05). Furthermore, the MVD of NSCLC displaying bFGF-positive /EGFR-positive was higher than that of the inverse conditions (P<0.05). In addition, the result of laser scanning image showed that vascular system of the experimental tumors were thicker, and the density was higher than the controls (P<0.05).
Conclusions It was suggested that overexpression of bFGF and EGFR were related to the differentiation, clinical stage, angiogenesis and lymph node metastasis of NSCLC. To detect the expression of bFGF, EGFR and count the
MVD may present more reference and biological information in pathological diagnosis, evaluation of prognosis and clinical treatment of NSCLC. In addition, LSCM was valuable to check the spatial structural relationship of the lung carcinoma vascular system, and may provide a new method for further investigating the neoplastic angiogenesis in vivo.
方法：用免疫组化SP法检测62例非小细胞肺癌和10例良性病变肺组织中bFGF、EGFR和CD34的表达，计数肿瘤MVD，并用原位杂交法检测肺癌组织中bFGF mRNA表达。建立荷瘤鼠肺癌移植瘤模型，利用激光共聚焦扫描显微镜对肿瘤血管连续断层扫描，比较实验组与对照组肿瘤血管的差异。
结果：bFGF、EGFR表达及MVD计数与非小细胞肺癌的分级、TNM分期及淋巴结转移呈正相关，在Ⅲ级高于Ⅰ～Ⅱ级、TNM分期的Ⅲ～Ⅳ期高于Ⅰ～Ⅱ期，有淋巴结转移组高于无淋巴结转移组，差异具有统计学意义(P＜0.05)。bFGF+/EGFR+的NSCLC，其MVD明显高于bFGF-/EGFR-组的MVD(P＜0.05)。荷瘤鼠肺癌血管在体扫描成像结果显示，实验组肿瘤血管较对照组粗大，血管密度增高，差异具有统计学意义(P＜0.05)。
结论：bFGF、EGFR高表达与NSCLC的分化程度、临床TNM分期、血管生成及淋巴结转移关系密切，联合检测bFGF、EGFR表达及MVD计数有助于评价NSCLC的生物学行为及预后。激光共聚焦扫描显微镜能直观、动态地反映肿瘤血管的走行及空间结构关系，为活体肿瘤血管的研究提供新的手段。
Purpose The purpose of this research was to explore the relationship of basic fibroblast growth factor (bFGF) and epidermal growth factor receptor (EGFR) with angiogenesis and lymph node metastasis of non-small cell lung cancer (NSCLC), and to analyze the blood vessel imagings of lung cancer transplanted BALB/c mice in vivo.
Methods The expression of bFGF, EGFR and CD34 was examined by immunohistochemical technique in 62 NSCLC and 10 benign lung lesions. In situ hybridization was used for further detecting of bFGF mRNA expression. In addition, the animal model of lung cancer transplanting BALB/c mice was established, and laser scanning confocal microscopy (LSCM) was used to scan continually the superficial vascular system of lung cancer in BALB/c mice to distinguish the difference between the experimental and the control groups in vivo.
Result The level of bFGF, EGFR protein expression and the microvessel density (MVD) of tumor tissues in differentiated grading III were remarkably higher than in differentiated grading I~II, and remarkably higher in III-IV stage than in I~II stage, and significantly higher in lymph node metastasis group than in non-metastasis group (P<0.05). Furthermore, the MVD of NSCLC displaying bFGF-positive /EGFR-positive was higher than that of the inverse conditions (P<0.05). In addition, the result of laser scanning image showed that vascular system of the experimental tumors were thicker, and the density was higher than the controls (P<0.05).
Conclusions It was suggested that overexpression of bFGF and EGFR were related to the differentiation, clinical stage, angiogenesis and lymph node metastasis of NSCLC. To detect the expression of bFGF, EGFR and count the
MVD may present more reference and biological information in pathological diagnosis, evaluation of prognosis and clinical treatment of NSCLC. In addition, LSCM was valuable to check the spatial structural relationship of the lung carcinoma vascular system, and may provide a new method for further investigating the neoplastic angiogenesis in vivo.
引文
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