[Expression of carbonic anhydrase IX in NSCLC and its relationship with VEGF and Ki67 expression]

Zhongguo Fei Ai Za Zhi. 2010 Sep;13(9):861-6. doi: 10.3779/j.issn.1009-3419.2010.09.05.
[Article in Chinese]

Abstract

Background and objective: It has been shown that carbonic anhydrase IX (CAIX) was closely related to tumor hypoxia. Proliferating cell nuclear antigen (Ki67) is considered to be an objective indicator which could reliable and comprehensive response to cell population proliferation; vascular endothelial growth factor (VEGF) was positively correlated with tumor angiogenesis. The aim of this study is to investigate the significance of the expression of CAIX in non-small cell lung cancer (NSCLC) tissues by analyzing the correlation between CAIX and clinical characteristics of patients with lung cancer and VEGF, Ki67 expressions.

Methods: CAIX, VEGF and Ki67 protein were detected in 76 cases of NSCLC and 10 cases of lung inflammatory pseudotumor by immunohistochemistry.

Results: CAIX was expressed in 45 of 64 cases of NSCLC and not expressed in benign lesion pulmonary tissues. VEGF was expressed in 55 of 76 cases and Ki67 was expressed in 30 of 76 cases. The expression of CAIX in squamous cell carcinoma (SC) was higher than that in adenocarcinoma (AC) (69.7% vs 27.9%, P=0.001). In 34 cases who received radiotherapy, the objective response rates of CAIX positive and negative groups were 27.8% and 62.5% respectively; the expression of CAIX was positively correlated with VEGF (r=0.231, P=0.043) and was not correlated with Ki67 (r=0.064, P=0.583).

Conclusions: Compared with benign lesion pulmonary tissue, the expression of CAIX in NSCLC tissues is significantly increased and is positively correlated with VEGF. The expression of CAIX was also correlated with the objective response rate of radiotherapy, which provided new evidence about that hypoxia can increase NSCLC radiotherapy resistance.

背景与目的: 已有的研究表明CAIX与肿瘤的乏氧代谢密切相关,细胞核增殖抗原(proliferating cell nuclear antigen, Ki67)被认为是能较可靠、全面地反映细胞群体增殖活性的客观指标;血管内皮生长因子(vascular endothelial growth factor, VEGF)与肿瘤血管生成呈正相关,本研究通过分析其与肺癌患者临床特点及与VEGF、Ki67表达的相关性,了解CAIX在非小细胞肺癌(non-small cell lung cancer, NSCLC)组织中表达的意义。

方法: 应用免疫组化SP方法检测76例NSCLC组织(33例鳞癌、43例腺癌)中CAIX、VEGF和Ki67表达及10例肺炎性假瘤中CAIX表达。

结果: 76例NSCLC组织中CAIX、VEGF和Ki67表达阳性率分别为46.1%、72.4%和39.5%;肺癌组织中CAIX表达明显高于炎性假瘤组(P<0.001);CAIX蛋白阳性表达率在鳞癌组和腺癌组表达分别为69.7%和27.9%(P=0.001);在接受放疗的34例患者中,CAIX阳性组和阴性组放疗客观反应率分别为27.8%和62.5%(P=0.042);CAIX蛋白表达与VEGF表达呈正相关(r=0.231, P=0.043),但与Ki67表达无相关性(r=0.064, P=0.583)。

结论: CAIX在NSCLC组织中表达较良性组织水平明显上升,并与VEGF表达相关;CAIX蛋白表达与放疗客观反应率相关,为乏氧增加NSCLC的放疗抗拒提供了新的证据。

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / genetics
  • Carbonic Anhydrases / metabolism*
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism*
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Antigens, Neoplasm
  • Ki-67 Antigen
  • Vascular Endothelial Growth Factor A
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases

Grants and funding

本研究受首都医学发展科研基金(No.20073042)资助