Expressions Of RKIP In Laryngeal Squamous Cell Carcinoma

Objective: Laryngeal cancer is a kind of malignant tumor originating from laryngeal epithelium. It continues to be one of the most common malignant tumors of the head and neck. And the incidence of laryngeal cancer is relatively high. The causes of laryngeal cancer include smoking, excessive drinking, air contamination, vocational factor, viral infection, radioactive ray and so on. Over the years, the incidence of laryngeal cancer is increased gradually. The primary methods of treatment consist of operation, radiotherapy etc. Metastasis is the main cause of death laryngeal cancer. Raf-1 kinase inhibitor protein (RKIP) are expressed in many tissues, such as the testis, adrenal gland, liver, and kidney. Species of RKIP show a high degree of sequence similarity with important biological functions. Recently, it has been discoverd that RKIP could inhibit metastasis in prostatic carcinoma, colorectal cancer, breast cancer and malignant melanoma. Therefore, RKIP has been recognized as a strong candidate for a metastasis suppressor gene in malignant tumors, however the mechanism of metastasis inhibition remains unclear. RKIP participates in many signal pathways, playing important roles in vivo. For example, RKIP could inhibit mitogen-activated protein kinase (MAPK) signal pathway, that regulates many fundamental cellular functions, such as proliferation, transformation, and apoptosis. This pathway is altered in 30% of all cancers in which MAPK is activated implicating in oncogenic transformation, invasion and metastasis. Execution of intracellular signaling achieved by a cascade of Raf/ MAPK kinase (MAPKK)/ extracellular signal-regulated kinase (ERK) activation. This includes phosphorylation and activation of MAPK kinase by Raf followed by phosphorylation and activation of ERK by MAPK kinase. Our study is to investigate the expression and its clinical significance of RKIP in laryngocarcinoma so as to elucidate whether RKIP plays a role in inhibition of metastasis by MAPK pathway. Methods: 41 cases surgically resected laryngeal carcinomas were gathered at Department of Otolaryngology Head and Neck Surgery, Bethune International Peace Hospital. All patients had received neither chemotherapy nor radiation therapy before tumor resection. Immunohistochemistry was used to detect the expressions of RKIP and P-ERK in laryngocarcinoma ,lymphnode metastases and normal laryngeal squamous epithelium from 41 laryngocarcinoma patients.Results:1 Expression of RKIP1.1 In normal laryngeal squamous epithelium, RKIP was expressed in the cells of spinous layers, granular layers but not in the basal layer. In well differentiated laryngocarcinoma, RKIP was expressed in the spinous-like, granular-like tumor cells, but not in basal-like tumor cells. However, RKIP expression was negative in poor differentiated laryngocarcinoma.1.2 Statistical analysis revealed that RKIP positive staining rate was lower in laryngocarcinoma than that in normal laryngeal squamous epithelium. The difference was significant (P=0.012). In 41 laryngocarcinoma patients, RKIP positive staining rate was lower in node-positive tumors than that in node-negative tumors. The difference was significant (P=0.016). There was no significant difference of RKIP expression between primary tumors and lymph node metastatic tumors. RKIP expression is not related with sex, age, site of primary tumor, T stages and clinical stages.2 Expression of P-ERKIn normal laryngeal squamous epithelium, P-ERK was expressed in the cells of basal layer and spinous layers. In laryngocarcinoma, P-ERK expression was observed in majority of cases.3 Correlation analysisIn primary laryngocarcinoma, RKIP expressions had positive correlation with P-ERK expressions (P=0.003, r=0.456).Conclusion:1 RKIP expression was significantly decreased in laryngocarcinoma compared with that in normal laryngeal squamous epithelium.2 The primary laryngocarcinomas with reduced levels of RKIP expressions had a higher tendency to metastasize.3 RKIP expression does not related with sex, age, site of primary tumor, T stages and clinical stages.4 In addition to the regulation of the MAPK pathway, RKIP fulfils another yet unknown function that impedes metastasis.