The Study Of Prognostic Molecular Markers In Primary Glottic Larynx Squamous Cell Carcinoma

Background :Head and neck cancer is the sixth most common malignant tumor,and the most common pathological type is squamous cell carcinoma. The laryngeal squamous cell carcinoma(LSCC) is the second most common head and neck squamous cell carcinoma(HNSCC), after nasopharyngeal carcinoma, the incidence rate is 5.7% to 7.6% in all malignant tumors. In American, new cases is about 12000 cases each year, about 4000 patients will death. The incidence is also gradually increasing in China. In recent years, although the improvement of treatment of laryngeal carcinoma, the survival time was not prolonged. In advanced HNSCC, more than 50% of the patients had local recurrence or distant metastasis, and the recurrence / metastasis is a major cause of treatment failure and poor prognosis. With the development of molecular biology, previous research has found many biomarkers that are associated with recurrence,metastasis and prognosis, including EGFR, c-Met, CD44, VEGFR, PI3 K, Notch1 and so on, but they are lack of specificity. C-Met and EGFR is considered closely related to recurrence or metastasis in HNSCC, and can be used as an independent predictor of DFS and OS. Because of head and neck squamous cell carcinoma has a characteristic that Anatomical diversity lead to different molecular biological mechanism, so the role of gene in predicting the prognosis is not clear in glottic LSCC, and further research is needed. EGFR and c-Metpurpose:1.To investigate the relationship between the expression of EGFR and c-Met and clinicopathological factors in glottic LSCC2. To investigate the relationship between the expression of EGFR and c-Met and DFS、OS in glottic LSCC,and another objective is to investigate role of Combined with EGFR and c-Met expression in predicting the DFS and OS of glottic LSCC.meathors:1. Collected 71 cases of surgically resected pathological specimens of patients with glottic LSCC, and the clinical pathological data such as age, Smoking, drinking, TNM stage, pathological grade and so on.2. Immunohistochemistry were used to detect the expression of EGFR and c-Met in primary glottic LSCC, IHC results were evaluated by H score.3. SPSS 16.0 statistical software was used to statistical analysis.Results:1. 71 cases of glottic LSCC were Collected, 29 patients with local regional recurrence, 5 patients with distant metastases(mainly lung metastases), 5 patients with second primary tumor, and 32 patients without disease progression during follow-up. all patients are male, The median age was 60 years(range 39-79).2. Specific colored of C-Met and EGFR are mainly located in the cell membrane, part of a cytoplasmic coloration, Their positive expression rates are 69% and 91.5% respectively.3. In this study, The median value of H-score of c-Met and EGFR are respectively160(range: 0~270) and240(range: 0~300). The results of Clinicopathological factors and c-Met expression and EGFR expression correlation analysis show: Patients with relapse have a higher EGFR expression and c-Met expression(p = 0.001, p <0.001), Age and T stage correlated with c-Met expression(p = 0.014, p = 0.06), but no significant correlation with EGFR expression(p = 0.262, p = 0.200), The rest clinicopathological factors have no significant correlation with c-Met expression and EGFR expression and.4. In all 71 patients, the m DFS was 51.4 months(range:36.8-66.1 months), 3-year disease-free survival rate was 54.26%; m OS was 81.0 months, 1-year, 2-year and 3-year overall survival rates were 95.22%, 84.91%, 77.01%, respectively.5. Univariate COX regression analysis showed that C-Met high-expression and EGFR high-expression were closely related to shorter DFS(HR=4.785,P=0.000;HR=3.028, P=0.003)and OS(HR=6.976,P=0.002;HR=4.554,P=0.016) after laryngeal squamous cell carcinoma operation.6. multivariate COX regression analysis showed: C-Met high-expression is an independent risk factor for disease progression and death(HR = 4.050, P = 0.002; HR = 9.040, P = 0.008), In contrast, EGFR expression was not similar predictive value for DFS and OS(p = 0.352, p = 0.240). In a related clinical and pathological factors, only pathological grade and N grade can be used as an independent predictor of DFS(HR = 0.376, P = 0.014;HR=4.432,P=0.051),but not OS.7. The study also found that there is a positive correlation between the c-Met expression and EGFR expression(κ = 0.405, P = 0.001),but prognostic value of EGFR and c-Met combined is not superior to c-Met.8. After combined with EGFR expression and c-Met expression,the population was divided into 3 groups, OS and DFS of Low-risk group(Both are low expression) compared with medium-risk group(There is one high expression) or high- risk group(Both are high expression) was significantly longer(χ2 = 20.214, P <0.001;χ2 = 13.570, P = 0.001).Conclusions:1. Clinicopathological factors is worse than molecular biomarkers on predictive value of prognostic, c-Met expression has independent predictive value for DFS and OS.2. c-Met expression and EGFR expression were closely related to DFS and OS after glottic LSCC operation,but the predictive value of c-Met expression better than EGFR expression on predicting risk of recurrence and death of glottic LSCC.3. There was a positive correlation between C-Met expression and EGFR expression,but c-Met and EGFR combined do not improve the accuracy of prognosis eval uation.