Factors Of Lymph Node Metastasis In Patients With Gastrointestinal Stromal Tumors

BACKGROUND: Gastrointestinal stromal tumors(GISTs)are a distinct type of mesenchymal tumor of the gastrointestinal(GI)tract,which account for about 1 –3% of all gastrointestinal tumors.As presently understood,GISTs originate from the cajal cells of the interstitum of the gastrointestinal tract.GIST can occur anywhere within the digestive tract,with the most common primary tumor site being the stomach(70%),followed by the intestines(20%).Many GISTs can present with metastasis,which primarily spread to the peritoneal envelope and liver in a highly invasive fashion.However,GIST with lymph node metastasis(LNM)is uncommon,so nodal dissection is generally not recommended for the surgical treatment of GIST.E-cadherin is a calcium-mediated cell adhesion molecule,playing a key role in maintaining cell-cell adhesion.It has been shown that the expression of E-cadherin will be down-regulated when carcinoma cells undergo an epithelial-mesenchymal transition(EMT).Cyclooxygenase-2(COX-2)is a rate-limiting enzyme for the synthesis of prostaglandin,which has been found to be overexpressed in many malignant tumor types.In addition,vascular endothelial growth factor(VEGF)can promote angiogenesis,which is thought to be an essential step in promoting tumor development and the formation of metastasis.Matrix metalloproteinase-9(MMP-9)is a member of the matrix metalloproteinases family,which can degrade the extracellular matrix to facilitate tumor invasion and metastasis.These 4 factors are intimately correlated with malignant tumor development and metastasis,but the relationship of these 4 factors with lymph nodes metastasis in GIST is still unknown.OBJECTIVE: To explore the clinicopathological features of gastrointestinal stromal tumor(GIST)presenting with lymph node metastasis.METHODS: We retrospectively collected all patients who were diagnosed with GIST between 2005 and 2016 at Wuhan Union Hospital.We then subdivided patients into 2 unique groups based on lymph node metastasis(LNM)status: the metastatic group(MG),where patients had lymph node metastases,and the non-metastatic group(NMG),where patients did not have lymph node metastasis.We then analyzed the clinicopathological features between the MG and NMG groups,such as age,gender,tumor size,tumor location,mitotic index,etc.In addition,we obtained GIST tissue specimens from both groups and performed immunohistochemical staining of COX-2,MMP-9,VEGF,and E-cadherin to analyze the relationship between the expression levels of these proteins and enzymes,and LNM status.RESULTS: Patient phenotype and hemoglobin concentration are two independent risk factors that predict GIST with LNM.COX-2 and E-cadherin can promote LNM in GISTs.CONCLUSIONS: Expression of COX-2 and E-cadherin in MG is considerably higher than NMG and may contribute to LNM in GISTs.