HIF-1α Protein Expression And Functional Vascular And Lymphatic Vessel Number In Non-small Cell Lung Cancer

Objective Lung cancer is the leading malignant tumor in China with both morbidity and mortality.Non-small cell lung cancer accounts for 80 to85% of lung cancers.The expression of Hypoxia-inducible factor-1α(HIF-1α)protein is closely related to angiogenesis and poor prognosis of NSCLC patients.However,the expression of HIF-1α protein in the nucleus of NSCLC has not been reported.In this study,the expression of HIF-1α protein in the nucleus of NSCLC and the number of functional blood vessels and lymphatic vessels were studied by surgical specimens of lung adenocarcinoma and the establishment of transplanted tumor models of lung adenocarcinoma A549,LU65 and LU99.Methods The expression of HIF-1α protein in lung adenocarcinoma cells was studied by immunohistochemical staining and statistical methods.Lung adenocarcinoma specimens were selected,and lung adenocarcinoma A549 cells,large cell lung cancer LU65 and LU99 cells were injected subcutaneously into the back of nude mice to establish the xenograft tumor model.The expression of HIF-1α,Albumin,Ig M and LYVE-1 proteins was analyzed by HE staining and immunohistochemistry(IHC).Results1.HIF-1 α protein was highly expressed in 98% of invasive lung adenocarcinoma cells by immunohistochemical staining,and the positive rate of HIF-1α protein was 10%(14/138).In addition,15% of cancer cells in clinical infiltrating lung gland specimens showed low expression of light brown,and the positive rate of low expression was78%(107/138 cases).In addition,in a small number of invasive lung adenocarcinoma specimens,100% of the cancer cells were negative and had no expression of HIF-1α protein,and the non-expression rate was 12%(17/138 cases).2.The expression of HIF-1 α protein in A549 transplanted tumor cells was negative.The density of Albumin and Ig M positive functional vessels in invasive lung adenocarcinoma tissues was higher than that in non-invasive lung adenocarcinoma tissues [(14.801.03)/HPF vs(3.50.53)/HPF,P<0.01].The density of LYVE-1 positive lymphatic vessels in invasive lung adenocarcinoma tissues was higher than that in non-invasive lung adenocarcinoma tissues [(25.94.43)/HPF vs(3.60.52)/HPF,P<0.01].3.HIF-1 protein expression was found in a few tumor nuclei in Lu65 xenografts,while no HIF-1 protein expression was found in Lu99xenografts(P < 0.05).Conclusions1.HIF-1α protein expression is related to cancer cell heterogeneity.2.The expression of HIF-1α is not related to functional vessel and lymphatic vessel density.3.Functional vascular and lymphatic vessel density is closely related to the invasion and development of lung adenocarcinoma.