Study On The Characterics Of Lymphangiogenesis In Laryngeal Squmous Cell Carcinoma

OBJECTIVE: To study the characteristics of lymphangiogenesis in laryngeal carcinoma, and their relationship with clinical pathological factors to provide theoretic evidence for the further study of lymphangiogenesis and anti-lymph node metastasis therapy in laryngeal squamous cell carcinoma (LSCC).METHODS: The micro-lymphatic density (MLD) and the micro-vascular density(MVD)in tumor and non-tumoral districts of 42 specimens of LSCC were evaluated by immunohistochemistry with monoclonal antibody for D2-40, a newly discovered lymphatic endothelial marker, and antibody for CD34 respectively. The proliferative activity of both lymphatic endothelial cells and blood vessel endothelial cells were detected by double-labeling immunohistochemistry, with antibodies for Ki-67 and D2-40 or for Ki-67 and CD34 in 30 LSCC specimens that were chosen from those 42 ones. Finally, the correlation between MLD or MVD and clinical pathological factors was analyzed with statistics methods.RESULTS:The MLD at tumor border (13.09±4.62) was significantly higher than that in tumor (6.51±3.14) and in normal laryngeal mucosa (4.27±2.76) (P<0.05). The lymphatic vessels at tumor border often had large and open lumina, and lymphatic involvement by tumor cells can be seen, while those in tumor had a reticular architecture with tiny and ill-defined lumina. The Ki-67 labeling index of lymphatic endothelial cells at tumor border(0.16±0.059) was significantly higher than that in tumor(0.09±0.06)and in normal mucosal (≈0) (P<0.05). The MLD at tumor border was significantly correlated with regional lymph node metastasis and lymphatic involvement by tumor cells(P<0.05), but not other clinical pathological factors such as gender, age, grade of tumor cell differentiation , tumor type, T stage and TNM clinical stage (P>0.05). The MVD at tumor border (22.65±9.79) was significantly higher than that in tumor (16.94±7.08) and in normal mucosal (11.11±9.72) (P<0.05).The MVD in tumor was significantly higher than the MVD in normal mucosal (P<0.05).The MVD at tumor border was significantly associated with T stage, but not with gender, age, grade of tumor cell differentiation, tumor type, lymphatic involvement by tumor cells and lymph node metastasis. There was no significant difference between the Ki-67 labeling index of blood vessel endothelial cells at tumor border (0.34±0.07) and that in tumor (0.32±0.16) (P>0.05). Both of them were significantly higher than that in normal mucosal (0.13±0.059) (p<0.05) There was only significant difference between MLD and MVD, but not significant correlation between them in LSCC. The logistic analysis showed that the increase of MLD at tumor border was the risk factor for lymph node metastasis.CONCLSION:(1)Neolymphatic vessels are seen in laryngeal squamous cell carcinoma, mainly at tumor borders. The high MLD at tumor borders is significantly associated with lymph node metastasis. Evaluation of MLD at tumor border may be useful in predicting lymph node metastasis in patients with LSCC.(2)Angiogenesis existed in LSCC, the MVD at tumor border was significantly associated with T stage, but not with other clinical pathological factors.( 3 ) The character of lymphangiogenesis is different from angiogenesis in LSCC. There was no significant correlation between them in LSCC.(4)Tumor cells may spread to regional lymph nodes through invading into the lymphatic vessels at tumor border. The increasing of MLD at tumor border may be the risk factor for lymph node metastasis of LSCC.