| Backgroud and Objective: Laryngeal carcinoma accounts for 1%～5% of the malignant tumors in human being, Laryngeal and laryngopharyngeal cancers continue to be the most common malignant tumors of the head and neck, squamous cell carcinoma was particularly prevalent. But the exact pathogenesis and prognostic factors is not yet clear, As the development of the molecular mechanism study of the carcinoma, looking for cancer related markers to predict the occurrence and prognosis of LSCC and provide the new way of effective treatment has been the focus of clinical research. C-met receptor was a member of the receptor tyrosine kinase family, which is known to have the effects of stimulation of cell motility, dissociation of epithelial sheets, invasion of cellular matrix, and induction of angiogenesis. Abnormal expression of c-met may lead to activation of downstream molecules and the development of tumor and metastasis.β-catenin, is a component of the E-cadherin/catenin complex which controls cell-cell adhesion, abnormal expression ofβ-catenin will enable the cell adhesion decline and the invasion and metastasis of cancer cells. Meanwhile abnormal expression of-catenin could activate Wnt signaling systems, which lead to cell proliferation and malignant transformation. Skp2 is an important component of the ubiquition-proteasome system, and are responsible for the periodic proteolysis of many regulators of the cell cycle and oncogene related agent. In tumors, abnormal expression of Skp2 can lead to the regulation or degradation of various factors disorders, leading to cell proliferation without control. In this study, the protein level expressed in the laryngeal squamous cell carcinoma was detected by immunohistochemistry, we explore the relationship between the histopathologic variables and the expression of the three agents, and analyses the expression correlation of the agents. To find out tumor markers which may be used to predict tumor genesis and metastasis of laryngeal carcinoma and to further the clinical cancer treatment services, and offer theory basis to further study of the molecule mechanism and treatment of laryngeal carcinoma.Method: the information and paraffin-embedded tumor samples of 57 cases laryngeal squamous cell carcinoma patients who were treated at the first affiliated hospital of the Zhengzhou University from January 2003 to December 2004 were collected. All accepted no therapy for the tumor before their surgery and were proved to be squamous cell carcinoma by pathology. Another 20 cases normal laryngeal mucous membrane or polyps of vocal cord were chosen as controls. The expression level of c-met,β-catenin,Skp2 was detected by S-P method of immunohistochemistry, The staining procedure was performed following the manufacturer's recommendations. SPSS10.0 for windows was applied to analyze the results of experiment. A value of P< 0.05 was considered significant difference.Results:1. The percentage of abnormal expression of c-met was 56.14% in Laryngeal carcinoma while 15% in Laryngeal mucosa or polyps of vocal cord, the difference was very significant (P<0.05). The level of abnormal expression of c-met was 37.5% in stage T1 /T2, 57.14% in stage T3/T4,25.93% in stage I～II, 83.33% in stage III～IV. The level of abnormal expression of c-met in well-differentiated, moderately differentiated, poorly differentiated laryngeal carcinoma was 42.42%, 70%, 100%, respectively. The level of abnormal expression of c-met in LSCC with lymph node metastasis was 77.27%, while 22.86% in LSCC without lymph node metastasis. The c-met abnormal expression was correlated with size of tumor, differentiation, lymph node metastasis and clinical stage(P<0.05). C-met in different age groups was not statistically significant.2. The level of abnormal expression ofβ-catenin in LSCC was higher than that in laryngeal mucosa or polyps of vocal cord (40.35% VS.0.00%). The difference was significantly different(P<0.05). The level of abnormal expression ofβ-catenin in well-differentiated, moderately-differentiated and poorly-differentiated laryngeal carcinoma was 22.27%, 50%, 100%, respectively. Theβ-catenin abnormal expression in laryngeal carcinoma with lymph node metastasis was 68.18%, theβ-catenin abnormal expression in laryngeal carcinoma without lymph node metastasis was 22.86%. There is statistically significant association between theβ-catenin abnormal expression and histodifferentiation and lymph node metastasis(P < 0.05). No statistically significant association was found in different age groups, clinical stage and size of tumor.3. The level of abnormal expression of Skp2 in laryngeal carcinoma was higher than that in laryngeal mucosa or polyps of vocal cord (43.86% VS.10%). The difference was significantly different(P<0.05). The level of abnormal expression of Skp2 in well-differentiated, moderately-differentiated and poorly-differentiated laryngeal carcinoma was 30.30%, 60%, 75%, respectively. The Skp2 abnormal expression in laryngeal carcinoma with lymph node metastasis was 72.73%, the Skp2 abnormal expression in laryngeal carcinoma without lymph node metastasis was 25.71%. The level of abnormal expression of Skp2 was 70.37% in stage I～II, 4.033% in stage III～IV, the difference was significant (P<0.05). There is statistically significant association between theβ-catenin abnormal expression and differentiation, lymph node metastasis and clinical stage. No statistically significant association was found in different age groups and size of tumor.4.Spearman rank correlation showed the abnormal expression of c-met was positively related to that ofβ-catenin (r_s =0.367, P<0.05), so was between c-met and Skp2 (r_s =0.354, P<0.05). There was positively correlation between the abnormal expression ofβ-catenin and Skp2 (r_s =0.426, P<0.05).Conclusion:1. The positive expression rate of c-met in LSCC is higher than that in Laryngeal normal tissue and polyp of vocal, and has a significant correlation with the differentiation, lymph node metastasis and clinical stage, which suggest that c-met is involved in the incidence, development and metastasis of carcinoma, the high expression of c-met protein in LSCC may be considered as an indicator for prognosis of LSCC. the way to inhibit expression of c-met may be one new strategy of tumor therapy.2. the positive staining ofβ-catenin located in cell membrane in laryngeal normal tissue and polyp. Abnormal expression ofβ-catenin in LSCC included membrane decreased expression and ectopic expression, and has a significant correlation with differentiation and lymph node metastasis, suggested the cell adhesion weakened or lost and activation of Wnt pathway mediated byβ-catenin play an important role in incidence, poor differentiated and lymph node metastasis of LSCC. Abnormal expression ofβ-catenin may be an early event of LSCC.3. The positive expression rate of Skp2 in LSCC is higher than that in normal tissue and polyp of vocal, and has a significant correlation with the differentiated, lymph node metastasis and clinical stage, which suggested Skp2 protein promoted the incidence and development of LSCC, Skp2 protein may serve as the marker of proliferation of LSCC, and the Skp2 gene may be a new target of gene therapy4. In LSCC, there is a close relationship between the c-met expression, Skp2 expression and abnormalβ-catenin expression, suggested they play synergy in the incidence, development and lymph node metastasis of LSCC.
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