The Molecular Biological Study Of Invasion And Metastasis In Patients With Non-Small Cell Lung Cancer

PART 1 THE CLINICAL SIGNIFICANCE OF VASCULAR ENDOTHELIALGROWTH FACTOR AND INTERCELLULAR ADHESIONMOLECULE-1 EXPRESSION IN HUMAN NON-SMALLCELL LUNG CANCERObjective: To investigate the expression of VEGF and ICAM-1 in tumortissue of non-small cell lung cancer, and their relationship to behaviors of the non-small cell lung cancer.Method: A rapid immunohistochemical method (streptoavidin-peroxidase, SP) was used to detect VEGF and ICAM-1 expression in pathological tissue sections of 86 cases with non-small cell lung cancer. All patients were treated with operation and without radio- or chemical therapy before operation. The relationship between the expression and the histopathological type, stage, lymph node metastasis and survival time were analyzed with x test, Kaplan-Meier and Log Rank test.Results: The expression rates of VEGF and ICAM-1 in 86 NSCLC tissueswere 65% and 37% respectively. There was no significant difference among histopathological type in the expression of VEGF and ICAM-1. The positive expression of VEGF was significantly correlated with the lymph node metastasis, TNM stage, prognosis and hematogenous tumor metastasis positively. The 5-yearsurvival rate of patients with VEGF positive was significantly lower than that of VEGF negative patients. The positive expression of ICAM-1 was significantly correlated with the lymph node metastasis, TNM stage, prognosis and hematogenous tumor metastasis negatively. The 5-year survival rate of patients with ICAM-1 positive was significantly higher than that of ICAM-1 negative patients. In all patients, those with positive expression of VEGF and negative expression of ICAM-1 had the shortest survival time.Conclusion: The expression of VEGF and ICAM-1 correlated with the malignant behavior of non-small cell lung cancer. Examination of VEGF and ICAM-1 in NSCLC helped to evaluate its intensity of lymph node metastasis, TNM stage, and prognosis exactly, meanwhile to instruct the reasonable treatment. VEGF and ICAM-1 may play an important role in the biological behavior and prognosis of non-small cell lung cancer, and influence each other in the invasion and metastasis of non-small cell lung cancer.PART 2DETECTION OF CK19 mRNA IN PERIPHERAL BLOOD OF PATIENTS WITH NON-SMALL CELL LUNG CANCER BY ASSAYS OF REVERSE TRANSCRIPTION-POL YMERASE CHAIN REACTIONObjective: To investigate the CK19 mRNA expression in peripheral bloodand its significance in patients with non-small cell lung cancer. To establish a diagnostic method for lung cancer micrometastasis in peripheral blood.Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) wasused to amplify the CK19 mRNA in blood samples from 43 patients with non-small cell lung cancer, 20 cases with benign lung diseases, and 20 healthy volunteers.Results: Samples were diagnosed CK19 mRNA positive when 308 bp bandappeared in RT-PCR end product. The positive rates of CK19 mRNA in peripheral blood were 56% in patients with lung cancer, 10% in patients with benign lung diseases, but no sample was positive for CK19 mRNA in healthy volunteers, showing a significant difference between lung cancer and benign lung diseases, and between lung cancer and healthy controls (PO.Ol). In lung cancer group, the positive rate of patients with lymph node metastasis was 66%(21/32), which was much higher than those without lymph node metastasis (*2=6.65, 0.0KPO.05). The expression of CK19 mRNA in patients with I ,11 and III stage were 10%, 63% and 89% respectively. The positive rate had significant correlation with the TNM staging( a:2=18.03, P<0.0l), but histopathologic types( at2=0.18, P>0.05).Conclusion: RT-PCR amplification of CK19 mRNA is a sensitive method to early detect circulating cancer cell for patients with non-small cell lung cancer. It may be very useful in earlier diagnosis of micrometastasis and help doctors to evaluate the cancer more correctly and make the best treatment plan. Further studies with more samples and long-term follow-up are needed.PART 3THE CLINICAL SIGNIFICANCE OF VEGF-C mRNA AND ICAM-1 mRNA EXPRESSION IN PATIENTS WITHNON-SMALL CELL LUNG CANCER Objective: To investigate the expression of VEGF-C mRNA and ICAM-1mRNA in patients with non-small cell lung cancer, and their relationship to behaviors of non-small cell lung cancer and clinical significance.Method: Expression of VEGF-C mRNA and ICAM-1 mRNA was detected by RT-PCR in 43 patients with non-small cell lung cancer and 43 normal lung tissues. Their relation to biological behavior was evaluated with x 2 test.Results: Expression of VEGF-C mRNA and ICAM-1 mRNA were shown in 70% and 51% non-small cell lung cancer respectively. Both of them were much more different from their expression in normal lung tissues (PO.01). There were no difference in patients with different histological categories about expression of VEGF-C mRNA and ICAM-1 mRNA (P>0.05). The positive rate of VEGF-C mRNA expression is 88% in patients with lymph node metastasis and 18% in patients without lymph node metastasis (PO.01). The positive rate of ICAM-1 mRNA expression is 41% in patients with lymph node metastasis and 82% in patients without lymph node metastasis (0.01