Expression Of COX-2, VEGF-C And VEGFR-3 In Non-Small Cell Lung Cancer

Background and ObjectiveRecent years, incidence and mortality of lung cancer in many countries and regions have leapt to the top with rapid growth, but its curative efficacy is not satisfactory. Invasion and metastasis are major reasons of treatment failure and death, angiogenesis and lymphangiogenesis play a key role in the pathogenesis. Lymphatic metastasis of malignant epithelium tumor is not only the most common spread pathway, but also a major factor affecting recurrence and prognosis. Lymph vessel hyperplasia and expansion is often found in tumor stroma with lymph node metastasis.Vascular endothelial growth factor C (VEGF-C) is the main control factor to promote lymphatic vessel formation and highly expressed in a variety of tumor tissue. Binding with its receptor ~ vascular endothelial growth factor 3(VEGFR-3), VEGF-C exclusively stimulates epithelial proliferation, and induces lymphangiogenesis lymphatic vessel expansion, thereby promoting tumor microlymphatic generation.Cyclooxygenase-2 (COX-2) overexpresses throughout the entire process of genesis and development. It may promote the generation and metastasis of cancer in various ways, with important roles in tumor angiogenesis and lymphangiogenesis.It has important significance for lymphatic metastasis to study expression of COX-2, VECF-C and VEGFR-3 in non-small cell lung cancer (NSCLC). To understand the clinic significance, expressions of COX-2, VEGF-C and VEGFR-3 were detected in NSCLC and analyzed with their clinicopathological parameters. Meanwhile, by determination of microlymphatic vessel density (MLVD), we studied the correlation with lymphangiogenesis and lymph node metastasis, and explored their roles in lymphatic metastasis of malignaint tumors,Materials and Methods1. As test group, 65 cases of paraffin-embedded specimens were selected, in which were obtained from postoperative patients in the Thoracic Surgical Department of Second Affiliated Hospital of Zhengzhou University during 2003-2006 years, and confirmed pathological diagnosis of NSCLC. 16 cases of normal lung tissue were chosen as control group, which were obtained from patients with NSCLC 5cm far from tumor tissue and confirmed histologically. Any chemotherapy and radiotherapy have never been carried out in all cases before operation.2. The expression of COX-2, VEGF-C and VEGFR-3 was detected by immunohistochemical staining SP method. The lymphatic vessel number in tumor was counted and determination of microlymphatic vessel density (MLVD) was evaluated.3. x~2 test, independent sample t-test and Spearman correlation analysis were performed with SPSS10.0,α= 0.05.Results1. Expression of COX-2 in NSCLC was higher than control group (76.9% vs 25%, P<0.05), and was positively related with expression of VEGF-C, MLVD, lymph node metastasis (P<0.05), but negatively related with tumor differentiation (P<0.05). The positive staining product is brown granules, mainly localized in cytoplasm of cancer cell.2. Expression of VEGF-C in NSCLC was higher than control group (72.3% vs 12.5%, P<0.05), and was positively related with expression of lymph node metastasis, TNM stage, tumor invasion, VEGFR-3 expression, MLVD (P<0.05), but negatively related with differentiation (P<0.05). The positive staining product is brown granules, mainly localized in cytoplasm of cancer cell.3. Expression of VEGFR-3 in NSCLC was higher than control group (53.8% vs 6.3%, P<0.05), and was positively related with lymph node metastasis, MLVD, tumor invasion and pathology type (P<0.05). The positive staining product is brown granules, mainly localized in cytoplasm of lymphatic endothelial cells and some cancer cells.4. Compared to control group, the mean of MLVD in NSCLC increased remarkably (29.32±7.14 vs. 10.63±5.80; P<0.05 ). The level of MLVD in NSCLC was positive relation with TNM stage, lymphatic node metastasis, invasion and expressions of COX-2, VEGF-C, VEGFR-3, but negative relation with differentiation in NSCLC tissue. VEGFR-3 positive lymphatic vessel was mainly found nearby cancer, especially infiltrated anterior tissue of cancer cell, with big lumina, thin wall and irregular shape, and part vessels were filled with cancer cell.5. VEGF-C expression was significantly positive relation with COX-2(r_s=0.277, P=0.026) and VEGFR-3(r_s=0.398; P=0.001) in NSCLC.Conclusions1. COX-2, VEGF-C and VEGFR-3 play key roles in the development, invasion and metastasis of NSCLC, and may be important indicators of treatment and prognosis.2. MLVD is a key factor of lymphatic vessel metastasis in NSCLC. Its increase prognosticate the appearance of lymphangiogenesis and lymphantic node metastasis, and may be an important indicator of monitoring of tumor cells and its prognostic.3. COX-2 may promote lymphangiogenesis and lead to tumor invasion and lymph node metastasis by upregulating VEGF-C expression in NSCLC...