Relationship Between Intratumoral Lymphangiogenesis Of Hypopharyngeal Neoplasm And Lymphatic Metastasis

Background:Hypopharyngeal neoplasm locates in the place where can not be discovered early,and liable to metastasis which is one of the important factors having negative effects on the prognosis of a paitent.Some statistics show that five-year survive rate of hypopharyngeal neoplasm patient between 28.6% and 59.1%.But those who has lymphatic metastasis have poorer prognosis than those who has not.For a long time, abundant researches were concerntrate on angiogenesis and hematogenous metastasis.Due to lack of marker of lymphatic vessel endothelium,researchs concerning lymphangiogenesis and mechanism of lymphatic metastasis still insufficiency. Recent researchs have found a distinctive marker of lymphatic vessel endothelium which is called D2-40.Compare with other markers of lymphatic vessel endothelium such as LYVE-1,podoplanin and Prox-1,D2-40 is more sensitive.Consequently, D2-40 can be uesd to not only observe the shape and distribution of lymphatic vessels, but also discuss lymphangiogenesis and lympgatic metastasis.A large number of researches show that basic fibroblast growth factor,VEGF-C,VEGF-D,COX-1 take part in tumor lymphangiogenesis,and play an important role in lymphatic metastasis. Anti-lymphangiogenesis will be one of the treatments to cure tumors.Objective:This study is design to observe the shape of lymphatic vessels stained by D2-40 both in the intratumoral and normal tissue, compare the expression of b-FGF and D2-40 between intratumoral and normal tissue respectively,count the lymphatic vessel density(LVD),and investigate the clinical pathology significance of D2-40,and then discuss the possible pathway of lymphatic metastasis, the mechanism of lymphangiogenesis in Hypopharyngeal neoplasm as well.Methods:This study contains a total of 47 specimens of hypopharyngeal neoplasm and accordingly normal tissues collected from October,2007 to September,2009 in Qilu hospital of Shandong University.And Immunohistochemical analysis was performed to these specimens to detected the expression of b-FGF and D2-40 between intratumoral and normal tissue.Meanwhile, Greespan semi-quantitative assessing was used to mark the cell staining intensity and percentage of positive cells,and Weidner mathod was used to count Lymphatic vessel density both in the intratumoral and normal tissue.Clinical pathological parameters were also analysed.Then, use SPSS 16.0 statistics software to analyse the results.Results:1.There was statistically difference between the positive rate of b-FGF in hypopharyngeal neoplasm tissue(82.98%) and normal tissue(8.51%). There was no statistically difference concerning b-FGF's expression between age,gender,T stage,differentiation of tumor(P>0.05).Those who had lymph node metastasis had a higher positive rate of b-FGF than those had not.2. lymphangiogenesis can be observed in hypopharyngeal neoplasm tissue and tumor cells could be found in some lumen.By contrast,majority of lymphatic vessels in mormal tissue were expansive.3. There was statistically difference between high expression of intratumoral lymphatic vessel density and lymphatic metastasis(P<0.05) while there is no significantly difference between intratumoral lymphatic vessel density and patient's age,gender,differentiation of tumor(P>0.05).4.The lymphatic vessel density of those who were b-FGF positive expression were higher than those who were b-FGF negative expression,the difference was statistically significant(P<0.05).Conclusions: The morphology of intratumoral lymphatic vessels resembles that of immature one which is different from those in mormal tissues.This result is in accord with that of foreign scholar's,and these lymphatic vesssels can be proved to be newly proliferate. And the result that high expression of intratumoral lymphatic vessel density is relate to lymphatic metastasis shows that tumor may matastasis through newly proliferating lymphatic vessels,and lymphatic metastasis may increase along with the increase of lymphatic vessel density.There were statistically differences between the positive expression and negative expression of b-FGF in Hypopharyngeal neoplasm tissue and normal tissue,suggesting that the high expression of b-FGF will induce tumor lymphangiogenesis.Thus, we can hold the idea that with the development of studies concerning lymphangiogenesis and mechanism of tumor regulation, restrain tumor lymphangiogenesis will be one of the treatments of patients with tumor.