The Relationship Between Tumor Stroma Ratio And Lymphangiogenesis、Angiogenesis

Objective:To evaluate the connection of the tumor stroma ratio (TSR) and lymphangiogenesis、angiogenesis in squamous carcinoma of the esophagus.Background:In the literature,TSR is proved as an independent prognostic factor in many human solid tumors, including the esophageal squamous cell carcinoma. There are many kinds of cells in the stroma of the tumor,such as endothelial cell, pericyte, carcinoma-associated fibroblast and tumor stromal stem cell、progenitor. These cells play very important roles in promoting tumor development, invasion, metastasis, angiogenesis and lymphangiogenesis. Angiogenesis is critical for the progress of tumor. Thanks to the chaotic architecture and blood flow, high vascular permeability and non-uniform surface markers, tumor cell can easily penetrate the vascular wall and migrate into the blood, circulate to all organs of human body to form metastases. Microvascular density has been used as a prognostic factor to evaluate a lot of tumors. Another way for tumor cells migrate is the lymphatic vessel. A major role of the lymphatic system is to collect interstitial fluid from peripheral tissues and to return it to the blood circulation, so tumor-associated lymphatic vessels drain interstitial fluid away from the tumor. This fluid may contain tumor cells and tumor-derived proteins and other molecules. Tumor cells that dissociate from the tumor mass and enter the lymphatic vasculature are transported with the flow of interstitial fluid to the lymph node that drains the tissue within which the tumor is located. The tumor cells may then go on to form secondary tumors within the lymph node. In turn, these lymph node metastases have the capacity to shed tumor cells into the efferent lymphatics, with the consequence that additional lymph nodes further down the drainage basin may become colonized with metastatic tumor cells. Tumor cells can also in principle access the blood circulation via the lymphatics, for example through anastamoses such as that formed between the jugular vein and the thoracic duct into which lymphatic fluid collected from peripheral tissues ultimately drains. Tumor cells that enter the blood circulatory system after trafficking through the lymphatics then have the opportunity to disseminate to many organs and form metastases there. Thus, tumor-associated lymphatics constitute a conduit for disseminating tumor cells that facilitate the formation of lymph node metastases, and in addition may have the potential to act as an intermediate way station or bridgehead on the way to the formation of metastases in many body organs. The importance of tumor lymphatics in disease outcome for cancer patients is underlined by the major prognostic role played by the presence of lymph node metastases for many different types of tumor.D2-40is a novel monoclonal antibody,which mainly labels the podoplanin on the surface of lymphatic endothelium. So, we can use D2-40to dye lymphatic endothelium, then count the lymphatic vessel density to evaluate the lymphangiogenesis, and CD34, which is specific for endothelial cells, to count the blood vessel density and then evaluate the angiogenesis.Methods:89patients with ESCC who underwent esophagectomy at the Department of Thoracic Surgery of the Qilu Hospital between January2007and December2007were selected. The paraffin-embedded specimens blocks were acquired from the Pathology Department of Qilu Hospital. Sections were immunostained by hematoxylin&eosin(for tumor stroma ratio)、D2-40(specific for lymphatic endothelial cell) and CD34(specific for endothelial cells).Results:1.The expression of TSR was related to the pT stage(P=0.020). For the lymphatic node ratio, or the pN stage, maybe there was a correlation(P=0.059).2.In the team of stroma poor, MVD X±s was19.40±6.47; in stroma rich, the number was21.64±9.68. Maybe there was a difference between the two groups, but not reach statistically significant(P=0.196). MVD was closely connected with pT status(P<0.05), but nothing on tumor length、differentiation grade and pN stage(Table1).3.1n the team of stroma poor, LVDX±s was3.76±3.56; in stroma rich, the number was5.46±4.27. And the difference between the two groups reaches statistically significant(P=0.050). No significant correlation was identified between LVD and tumor length, differentiation grade and pT stage(P>0.05), but showed a significant correlation with pN stage(P=0.026). 4.There are relationships between TSR and MVD、LVD, which reach statistically significant (P=0.024;P=0.049).Conclusion:The expression level of TSR is related to the malignant biological behavior of esophageal squamous carcinoma and tumor angiogenesis lymphangiogenesis。 TSR can be as a basis to predict the prognosis of esophageal squamous cell carcinomas and the therapy which targeted TSR may have clinical significance.