The Expression And Significance Of Extracellular Signal-regulated Kinase And Matrix Metalloproteinase In Adenoid Cystic Carcinoma Of Salivary Gland

As one of the most common malignant tumor of salivary gland, adenoid cystic carcinoma (ACC) taking up 21%-24% of all salivary gland carcinomas. With high invasive potential; it tends to invade blood vessels and nerves, prone to recurrence and distant metastasis at early stage of tumor growth.The occurrence of tumor involves a number of cellular affairs and physiological process, and disorder of cellular signaling pathway plays an important role. Mitogen-activated protein kinase (MAPK) signaling cascade is one of the two important signaling pathway participate in cellular survival and anti-apoptosis, certain signal molecular over-express or activated lead to abnormal cellular proliferation or transformation. As one of the most important signal transduction systems of organism, MAPK participate in many cellular physiological functions and process such as growth, development, division, differentiate cell cycle regulation and function synchronization of cells. Currently four subtypes of MAPK have been found and cloned, including ERK1/2, JNK, p38, ERK5. ERK1/2 is widely distributed, involved in meiosis, mitosis and regulation of late stage of mitosis. Many stimulus, including growth factor, cytokine, virus infection, transfectants, oncogenic compounds can activate ERK1/2.Researches showed that ERK1/2 is over-expressed or activated in many tumortissues such as hepatocellular carcinoma, breast cancer, squamous carcinoma of head and neck, prostate cancer and kidney cancer and cell lines, indicating abnormal regulation of ERK1/2 is closed related to the development and progression of malignant tumors.Matrix metalloproteinase(MMPs) is make up of a group of zinc and calcium dependent matrix degrading enzyme which have similar structure, it involved in many physiological and pathological process, including embryo development, remodeling of normal tissue, would healing, angiogenesis, arthritis and malignant tumors. As MMPs can degrade all the components of extracellular matrix(ECM), it is widely focused for its role in tumor invasion and metastasis. Capable of degrading base membrane mainly made up of type IV collagen, it has been revealed that over-expression of MMP-2 and MMP-9 is closely associated with tumor invasion, metastasis and prognosis of several kind of human malignant tumors.The research on ERK1/2 signaling pathway in tumor development mainly focused on common tumors of human body, the expression of ERK1/2 and its role in salivary gland tumors are seldom. It is still unclear that whether the activation of ERK1/2 signaling pathway regulate the proliferation of salivary gland tumor cells or involved in tumor invasion and metastasis. This study focus on the expression of phophorylated form of ERK1/2, MMP-2 and MMP-9 in adenoid cystic carcinoma of salivary gland histologically. 30 cases of adenoid cystic carcinoma of salivary gland and 10 cases of normal salivary gland as control were chosen, we investigated the immunostaining of ERK1/2, MMP-2 and MMP-9 in adenoid cystic carcinoma of salivary gland and control. In controls, 3 out of 10 cases were immunostainded with ERK1/2, ERK1/2 was mainly expressed in the cytoplasm of ductal epithelial cells and vascular endothelial cell; 2 out of 10 cases were immunostainded with MMP-2 and MMP-9, MMP-2 and MMP-9 were mainly expressed in the cytoplasm of ductal epithelial cells; in adenoid cystic carcinoma, 22 out of 30 cases were immunostainded with ERK1/2, ERK1/2 was expressed in the cellular nucleus of ductal epithelial cells, while 19 out of 30 cases were immunostainded with MMP-2 and 20 out of 30 cases with MMP-9, MMP-2 and MMP-9 were mainly expressed in the cytoplasm ofductal epithelial cells, myoepithelial cells and some stromal fibroblast. This study proved that: compare with normal salivary gland tissue, phophorylated form of ERK1/2, MMP-2 and MMP-9 were over-expressed in adenoid cystic carcinoma of salivary gland, indicating that ERK1/2, MMP-2 and MMP-9 may play important role in the development of adenoid cystic carcinoma. This study provide some information on the invasion and metastasis mechanism of adenoid cystic carcinoma of salivary gland, and the inhibition of ERK1/2 signaling pathway may influence the invasion and metastasis of adenoid cystic carcinoma.