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Clinico Pathological Analyses Of46Hypopharyngeal Carcinomas And Expression And Implication Of GLUT-1,HIF-1α In Head And Neck Squamous Cell Carcinoma

Posted on:2013-09-17Degree:MasterType:Thesis
Country:ChinaCandidate:Y Z LuoFull Text:PDF
GTID:2254330401957220Subject:Otorhinolaryngology
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BackgroundUp to now, the cause of hypopharyngeal carcinomas is unkown. Major risk factors for hypopharyngeal carcinomas are tobacco consumption, heavy alcohol drinking and poor nutrition, specifically low fruit and vegetable consumption. About of95%hypopharyngeal carcinomas are squamous cell carcinoma. It is less prevalent than other head and neck cancers, accounting for3-5%of all SCC in the region. Most patients when diagnosed have advanced-stage disease. Approximately70%to85%of the patients reported in large series have stage Ⅲ or Ⅳ disease at presentation, and the5-year overall survival rate is reported to bearound15%to45%. The prognosis is related to age, poor and late presentation of signs and symptoms of the disease and aggressive behavior of locoregional recurrence in the first two years, evolving with distant metastasis at initial presentation or during the disease progression. Distant metastasis is more likely to develop in advanced neoplastic disease and as first manifestation of failure of disease control, rates of43%of distant metastases being found in patients with squamous cell carcinoma of the hypopharynx and locoregional control of the disease. Among the prognostic factors in squamous cell carcinoma of the hypopharynx, the treatment protocols are also important factors. The main treatment protocols of hypopharyngeal carcinomas are surgery,radiotherapy and chemotherapy,and the tendency is combined modality therapy. Notwithstanding there are various kinds of treatment protocols of hypopharyngeal carcinomas, the prognosis is still poor, and the true cause of prognosis is till mistiness. Our study plan to analyze the correlation between clinicopathological factors and survival rate of hypopharyngeal carcinomas, to explore the correlation factors affecting prognosis.Materials and methodsIn the retrospective analysis,46patients with hypopharyngeal carcinomas from our departmen were collected between January2006and January2012. we observed the factors of patient’s age, gender, tumor differentiation, TNM classification, clinical stage, smoking, drinking, treatment, follow-up results, and analyze the correlation between various factors. Count data using the chi-square test, the survival rate using Life table methods, overall survival count using the Kaplan-Meier method, univariate analysis using the Log Rank method, multivariate analysis using Cox Regression proportional hazards model, p<0.05was statistically significant.Result1. Clinical features of46cases of hypopharyngeal46patients with squamous cell carcinoma of the hypopharynx were included in this study. There were44males, and2females. The age of patients ranged from43to77years, and the average was61.3years. The history rang from1month to10years. The symptom including Pharyngeal foreign body sensation, sore throat, hoarseness, dysphagia, difficulty swallowing, the repeated bloody sputum, difficulty swallowing, dysphagia et al.75.9%of the patients are smoker(35/46), and69.0%are alcoholisms (32/46). The sites of origin were pyriform sinus (n=35), postcrycoid area (n=1) and posterior pharyngeal wall (n=9), there was a case cannot detemine original site. The TNM categories:T1N0M08cases, T2N0M05cases, T3N0M06cases, T4N0M02cases, T1N1M02cases, T2N1M08cases, T3NiM06cases, T2N2M03cases, T3N2M01cases, T4aN1M02cases, T4aN2Mo2cases, TxN0M01cases; clinical stage Phase Ⅰ8cases, Ⅱ5cases,Ⅲ22cases and Ⅳa11cases. Among of all patients, well differentiated squamous-celled carcinoma, well-moderately differentiated, moderately differentiated, moderately differentiated-poor differentiated and poor differentiated squamous cell carcinoma were8,15,16,1and6cases.Among of46cases,21cases treated with surgical removal,20cases with surgery plus postoperative radiochemotherapy,5cases with only radiochemotherapy, and31cases (67.4%) preservation of laryngeal function. In15cases of total laryngectomy,5cases (33.3%) with pharyngeal fistula were cured after2weeks to six months of dressing and then can be a normal diet. In26cases treated with preservation of laryngeal function surgery,1case (3.8%) appeared postoperative bleeding and was stoped to bleed with surgery again.24cases of post-operative can normal eating without choking in14days, and two cases (7.7%) with cough recoved swallowing function with eating training in1to3weeks;25patients (96.2%) removed tracheal tube in2to3weeks afteroperation, and1case (3.8%) failed extubation due to bilateral vocal cord fixed in the middle of the bit, and was discharged wearing with tube.2. follow-up and survivalAll patients were followed to the September30,2012, up from3months to75months, with an average of31months. In46cases,11cases dead,4cases lost, the average median survival time was57.5months.11cases (23.9%) patients relapsed,4cases (8.7%) with distant metastasis are lung metastasis, and one of which combined with bone metastases.8cases (17.4%) were multiple primary cancers (multiple primary cancer, MPC),7of which were metachronous amphimorphic cancer, including4cases of esophageal cancer,1case of laryngeal cancer,1case of thyroid cancer and1case of lymphatic tumor;1case was metachronous treble cancer, surgery for prostate cancer in2006, discovered hypopharyngeal cancer and gastric cancer in August2009and March2010.Univariate analysis, the relationship between survival and clinical data:there was correlation between T stages and overall survival, the overall survival rate of T1+T2was55.6and T3+T4was35.0(p=0.029), the3-year and5-year survival rates of T1+T2were83.5%and55.6%, T3+T4were46.6%and35.0%; There was correlation between recurrence and survival rates, overall survival rate of recurrence was29.1%, and recurrence-free was51.8%(p=0.005), the3-year and5-year survival rates of recurrence-free were80.6%and51.8%, recurrence were29.1%and29.1%; Other indicators of age, tumor location, clinical stage, pathological grade, presence of distant metastasis, and presence or absence of multiple primary cancer, treatment with no significant correlation between overall survival rate. Cox Regression Multivariate analysis (due to fewer cases and using the Enter method), all factors affect survival rate (χ2-28.259, P=0.005), among of those factors,T classification had significant affecting with overall survival (p=0.033)Conclusion1. The data showed that there were recurrence in23.6%of hypopharyngeal and the incidence of MPC in hypopharyngeal carcinomas was17.4%.2. Univariate analysis showed there were correlation between overall survival rate and T stage or recurrence. Multivariate analysis showed that only T stage was independent factors affecting prognosis;3. Whether or not preserve laryngeal function, there was no effect on the survival rate of hypopharyngeal, it prompted that preserving laryngeal function in surgery is feasible Background:With development of immunology and molecular biology techniques, most scholars believed that tumor invasion and metastasis was a multi-factor, multi-step development process, and gene expression is one of the most important mechanism. Accordingly from the molecular level to explore HNSCC development mechanism was important for the understanding the pathogenesis, prognosis, and identifying potential therapeutic targets of HNSCC.Our previous study had found that there was relation between Glut-1expression and the biological behaviour of head and neck cancer, but there were controversial about that. Accordingly, the significance of Glut-1in HNSCC needed more research. HIF is regulator gene of Glut-1, HIF-1α and Glut-1are markers of tumor hypoxia, both increased expression means poorly prognosis of cancer. Rare reports about the correlation between the combination expression of both HIF-1α and Glut-1with biological behaviour of head and neck squamous cell carcinoma, and there were no similar report in hypopharyngeal carcinoma.This study using immunohistochemical methods to detect HIF-1α and Glut-1protein expression of hypopharyngeal carcinoma and laryngeal carcinoma, to analyze the relationship between the two proteins and the prognosis of HNSCC or other biological behavior, to explore the possible impact with HIF-la and Glut-1to HNSCC prognosis.Materials and methods69cases of head and neck cancer confirmed histologically, including23cases of hypopharyngeal squamous cell carcinoma,46cases of laryngeal cancer.control group:①15cases of polyps of the vocal cords confirmed histologically;(2)15cases of leukoplakia confirmed pathologically. The expression of HIF-1α and Glut-1protein expression of biopsy specimens of the above cases were examined by an EliVisionTM. To compare the differences between head and neck squamous cell carcinoma and vocal polyps or leukoplakia, and to analyze the correlation between clinicopathological factors, HIF-1α or Glut-1expression with survival rates. The correlation analysis between clinicopathological factors and Glut-1or HIF-1α using χ2test or Fisher exact test, α=0.05for the difference in the level of statistical significance testing, correlation analysis using Pearson test..Result:Glut-1immunohistochemical staining positive rate (72.5%) of Head and neck squamous cell carcinoma was significantly higher than that of the vocal cord polyps and mucosal leukoplakia (33.3%)(P<0.01). HIF-1α immunohistochemical staining positive rate (71.0%) of Head and neck squamous cell carcinoma was significantly higher than that of the vocal cord polyps and mucosal leukoplakia (13.3%)(P<0.01). Pearson Chi-Square analysis:The correlation with age, gender, location, T stage, N stage, case classification, recurrence and distant metastasis eight clinical factors and GLUT-1, HIF-1a were analysed by univariate analysis, results showed that Glut-1expression was correlated with location of the tumor, N stage and distant metastasis (P<0.05), HIF-1α expression was correlated with recurrence and distant metastasis (P<0.05). Among of69HNSCC cases, both Glut-1and HIF-1α were common positive expression in37cases. The Pearson correlation analysis:there were correlation between Glut-1and HIF-1α (r=0.338, P=0.004)The overall survival of69patients with head and neck squamous cell carcinoma were correlation with tumor primary site, T classification, clinical stage, lymph node metastasis, recurrence, distant metastasis, Glut-1positive expression and HIF-la positive expression. The3years,5-year survival rates of Glut-1positive expression of HNSCC patients were:46.7%,37.3%, Glut-1negative expression of HNSCC patients were:87.5%,82.4%; The3years,5-year survival rates of HIF-1α positive expression of HNSCC patients were:61.0%,42.7%, HIF-1α negative expression were:85.0%,78.5%. Multivariate proportional hazards model of Cox Regression Analysis:overall survival of patients were significantly correlation with the primary location of tumor (p=0.031) and tumor recurrence (p=0.000).conclusion1. The data showed that Glut-1, HIF-1α expression increased may be relevant to incidence of squamous cell carcinoma of the head and neck, there were greatly increased expression of Glut-1in head and neck squamous cell carcinoma than inflammatory lesions or precancerous lesions;2. There were correlation between increased Glut-1expression and the position or N stage or distant metastasis of head and neck squamous cell carcinoma; There were correlation between increased HIF-1α expression and recurrence or distant metastasis of head and neck squamous cell carcinoma;3. Univariate analysis showed there were correlation between Glut-1, HIF-1α expression,primary location of carcinoma, T stage,clinical state, lymph nodes metastasis, recurrence or distant metastasis with prognosis of head and neck squamous cell carcinoma; multivariate analysis showed that there were correlation between primary location of carcinoma or recurrence with prognosis of head and neck squamous cell carcinoma...
Keywords/Search Tags:Hypopharyngeal Cancer, survival rate, Prognosis, correlation analysis, head and neck squamous cell carcinoma, Glucose transporter-1, hypoxia induciblefactor-1α
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