The Character Of Lymphangiogenesis And Angiogenesis In Human Gastric Cancer And Their Relationship With Biological Features

AIMS:To investigate the distribution patterns,proliferative activity,their relationship with metastasis and clinicopathologic characters of lymphatic micro vessels and micro vessels in patients with gastric cancer. METHODS: The lymphatic micro vessel density (LMVD) and micro vessel density(MVD) of 56 cases of gastric cancers and 12 cases of normal gastric tissues were evaluated by immunohistochemistry, using monoclonal antibody for podoplanin and CD34 .The Ki-67 expression of the lymphatic lining cells and vascular lining cells were detected at the same time by double-staining immunohistochemistry . RESULTS: 1,The lymphatic micro vessel of normal gastric tissues can be seen at mucosa,submucosa,muscularis and serosa, the number of lymphatic micro vessel at submucosa is the most. The lymphatic vessels of intratumoral areas were not often seen and had ill-defined Lumina ,while at the same time,the peritumor lymphatic vessels had large and open lumina.The LMVD at peritumor regions (11.89±3.95 ) was significantly higher than that of intratumoral areas(5.83±3.26)(t=10.1,P<0.01) and normal gastric submucosa (6.93±1.32) (t'=7.52,P < 0.05).The Ki-67 labeling index of the lymphatic endothelial cells at peritumor region was significantly higher than that in normal gastric submucosa (t=6.88,P < 0.05) and intratumoral parts (t=6.38,P < 0.01). The LMVD at peritumor regions significantly correlated with differentiation of gastric cancers,lymphatic involvement by tumor cells and lymph nodes metastasis(F=14.96,t=4.11,4.51;P< 0.05,0.01,0.01). The peritumor Ki-67 labeling index of the lymphatic lining cells only significantly correlated with lymphatic involvement by tumor cells (t=3.73,P<0.01).2,The micro vessels of gastric cancers were tortured and usually had no lumina ,they could be seen both at peritumor and intratumor regions ,while at the same time ,the micro vessels of normal tissues had complete lumina. The MVD at peritumor regions (52±8.94) wassignificantly higher than that of intratumoral areas(37.6±9.85)and normal gastric tissues (23.2±3.19) (t=8.47,6.87;P<0.01,0.01).The Ki-67 labeling index of the vascular lining cells at peritumor region(0.02,0.01)was significantly higher than that of corresponding normal gastric tissues (0.003±0.002) and intratumoral parts (0.004±0.003) (t=3.64,11.64;P<0.01,0.01).The peritumor MVD significantly correlated with differentiation of gastric cancers and invasive depth(F=9.49,9.25;P<0.01,0.01). The peritumor Ki-67 labeling index of the vascular lining cells significantly correlated with differentiation of gastric cancers,invasive depth,PTNM staging and involvement of vascular vessels (F=5.61,19.38,t=2.49,4.27;P<0.01,0.01,0.05,0.01).CONCLUSIONS:1,The distribution patterns of lymphatic micro vessels in patients with gastric cancers are heterogeneous.lymphatic micro vessels at peritumor regions play an important role in lymphatic metastasis of gastric cancers, the detection of LMVD at peritumor regions may be useful in predicting differentiation of the tumor,lymph node metastasis and lymphatic involvement by tumor cells in patients with gastric cancers.2,The distribution patterns of micro vessels in patients with gastric cancers are heterogeneous.high proliferative activity of peritumor micro vessels promote vascular metastasis, and detecting MVD at peritumor region may be valuable in evaluating differentiation and invasive depth of gastric cancers.3,High proliferative activity of gastric cancer cells promote lymphangiogenesis and angiogenesis. 4,The use of double -staining immunohistochemistry with podoplanin and Ki-67,CD34 and Ki-67 could be more precise than common HE staining in predicting lymphatic and vascular involvement of tumor, thus could be useful in diagnosing lymphatic metastasis and neoplastic metastasis to distant portions.