The Expression And Clinical Significance Of HMGA2 And MMP2 In Non-small-cell Lung Carcinoma

Background & ObjectiveLung cancer is one of the common malignant tumors, which the morbidity and mortality showed a clear upward trend in the past few decades. Lung cancer in different organs of the transferred can display the different clinical manifestations due to the unrestricted tumor growth. However lung cancer does not lead to invasion and metastasis from carcinoma in situ (pre-invasion) to the development of invasive and metastatic cancer, which involves a wide range of host Interactions. From the pathological point of view, invasion and metastasis of lung cancer can be divided into the following stages:Primary cancer proliferation, angiogenesis; Destruction of basement membrane and invades the surrounding lung tissue; Invade into the lymphatic or blood; Stranded at the distance target organ; Distant metastasis.The growth of the body is inseparable from the surrounding angiogenesis. The one of reasons that the rapid growth of the tumor cell is the growth of tumor tissue are rich in blood vessels. These vessels provide for the growth of tumor tissue oxygen needs, growth factor levels of nutrients. Therefore, the ability to induce angiogenesis in tumor tissues made the premise of invasion and metastasis. How do tumor cells induce angiogenesis-level problems? Vascular endothelial growth factor (VEGF) is the one of a more current studies, which can change the form of endothelial cell gene activation, increase expression of fibrinolytic enzyme system and induce endothelial cells to produce proteolytic enzymes, interstitial collagenase and tissue factor, and then form new blood vessels. The high mobility protein (high mobility group protein A2, HMGA2) is found in the nucleus in recent years, a non-histone proteins. In embryonic development, the organizations expressed HMGA2 in a wide and high range, and in most normal adult tissues expressed in a low level. The studies of HMGA2 are few in lung cancer at present. This study makes use of immunohistochemical methods to analysis the expressions of MMP2 and HMGA2 in non-small cell lung cancer (Non-small-cell lung carcinoma, NSCLC) to explore the relationship of invasion, metastasis and the prognosis in the NSCLC patients, at the same time to provide a theoretical reference for clinical treatment.Materials & MethodsSamples of lung cancer and adjacent normal lung tissue were collected from 68 patients with NSCLC, diagnosed by pathology of surgical removed from March 2008 to October 2009 at the First Affiliated Hospital of Zhengzhou University.20 normal lung tissue were collected as control. Among them there were 29 males and 39 female, aged from 26 to 70 years old and the average age is 54. There were 30 squamous cell carcinoma cases and 38 adenocarcinoma cases, including 21 cases of well differentiated cell carcinoma,25 cases of moderately differentiated cell carcinoma and 22 cases of poorly differentiated cell carcinoma. Lymph node metastasis was observed in 37 cases, and without lymph node metastasis was 31 cases. Patients all were not carried out prior to radiotherapy and anticancer chemotherapy. Samples were fixed in 10% neutral formalin and embedded in paraffin.The expressions of HMGA2 and VEGF in lung cancerous tissue were detected by SP immunohistochemical method. Degree of staining is used to observe VEGF and HMGA2 expression in non-small cell lung cancer under the microscope.SPSS 17.0 software was used for statistical analysis,χ2 test and Fisher combined rank test. Spearman rank correlation analysis was used for correlation analysis. Significance level usingα=0.05.ResultsThe expression of HMGA2 in NSCLC:the positive rate of HMGA2 was 73.5% in samples of NSCLC tissues and 20% in normal lung tissues (P<0.05). The positive rate of HMGA2 in samples of lymph node was 86.5%, higher than the expression in the group without lymph node metastasis 38.7%(P<0.05). The positive rate of HMGA2 in samples of I and II clinical stage cases was 50%, lower than the expression in poor III and IV clinical stage lung cancer 85.7%(P<0.05). There were no statistical significance of difference in the expression of HMGA2 between squamous cell carcinoma and adenocarcinoma, male and female, smoker and non-smoker, younger and older. The expression of VEGF in NSCLC:the positive rate of VEGF was 76.5% in samples of NSCLC tissues and 40% in normal lung tissues (P<0.05). The positive rate of VEGF in samples of lymph node was 89.2%, higher than the expression in the group without lymph node metastasis 41.9%, (P＜0.05). The positive rate of VEGF in samples of I and II clinical stage cases was 52.5%, lower than the expression in poor III and IV clinical stage lung cancer89.3%, (P<0.05). There were no statistical significance between squamous cell carcinoma and adenocarcinoma, male and female, smoker and non-smoker, younger and older. The expressions of VEGF and HMGA2 in NSCLC were present at the same time, the Spearman rank correlation analysis showed that HMGA2 expression in NSCLC tissues and the expression of VEGF were positively correlated.Conclusions(1) HMGA2 showed a high level in non-small cell lung cancer. The non-small cell lung cancer with lymph node metastasis and the one with clinical stage were positively correlated. So HMGA2 may be involved in the development, invasion and metastasis process of non-small cell lung cancer. (2) VEGF showed a high level in non-small cell lung cancer. The non-small cell lung cancer with lymph node metastasis and the one with clinical stage were positively correlated. So VEGF may be involved in the development, invasion and metastasis process of non-small cell lung cancer. (3) HMGA2 and VEGF in non-small cell lung cancer tissues were positively correlated, suggesting that the two may promote each other in the development, invasion and metastasis of non-small cell lung cancer.