缺氧诱导因子1α和环氧化酶2在喉鳞癌组织中的表达及意义

目的 探讨喉鳞癌组织中缺氧诱导因子1α(hypoxia-inducible factor-1 alpha,HIF-1α)和环氧化酶2(cyclooxygenage-2,COX-2)的表达情况及其与患者临床病理资料的关系和对预后的影响.方法 免疫组化Envision二步法检测60例喉鳞癌标本中HIF-1α和COX-2蛋白的表达,15例不典型增生、10例声带白斑、10例声带息肉标本作对照.结合喉鳞癌患者临床和病理资料进行分析.结果 60例喉鳞癌组织中HIF-1α呈高表达为35.0%(21/60),COX-2高表达为38.3%(23/60).两者阳性表达率与不典型增生、声带白斑及声带息肉组相比差异均具有统计学意义(Fisher确切概率法,P值均<0.01).喉鳞癌组织中HIF-1α和COX-2的表达结果 呈正相关(r=0.526,P<0.01).喉癌HIF-1α高、低表达组在临床分期(X2=4.331,P<0.05)及淋巴转移方面(Fisher确切概率法,P<0.05)组间差异具统计学意义;COX-2高、低表达组在T分期及临床分期方面组间差异具统计学意义(X2值分别为6.792和8.539,P值均<0.01).单因素分析HIF-1α高、低表达组间生存率及无瘤生存率差异均具统计学意义(X2值分别为6.003和5.010,P值均<0.05),COX-2高、低表达组生存率差异及无瘤生存率差异均具统计学意义(X2值分别为9.489和6.102,P值均<0.05).多因素分析提示复发及COX-2表达是影响喉癌患者预后的重要危险因素(相对危险度分别为7.104和5.714,P值均<0.01).结论 HIF-1α和COX-2在喉鳞癌发生、发展中起重要作用,两者可能有协同关系.COX-2表达及肿瘤复发情况可能作为评估喉鳞癌预后的重要危险因素.

Expression and clinical significance of hypoxia-inducible factor-1α and cyclooxygenase-2 in laryngealsquamous cell carcinoma

Objective To investigate tbe expression of hypoxia-inducible factor-1 alpha (HIF-1α) and cyclooxygenase-2 (COX-2) in laryngeal squamous cell carcinoma (LSCC), while determine their relationship with clinicopathologic characteristics and prognosis. Methods Tumor tissues were obtained from 60 patients who underwent resection of laryngeal carcinoma in Affiliated First People's Hospital of Shanghai Jiaotong University. Immunohistochemistry (Envision DAKO) was used to detect the expressions of HIF-1α and COX-2 in the tumor tissues. As control group, 15 cases of atypical hyperplasia, 10 cases of leukoplakia of vocal cord and 10 cases of polyp of vocal cord were studied. All patients were regularly followed up and the clinical data were collected systematically. Results Positive staining rates of HIF-1α and COX-2 were 95.0% (57/60) and 98.3% (59/60), respectively in all 60 specimen of LSCC. The positive expressions in LSCC were significantly higher than those in atypical hyperplasia, leukoplakia and polyp of vocal cord(Fisher's exact test,P<0.01). The expression of HIF-1α was correlated with COX-2 in LSCC(r=0.526, P<0.01). High level expressions of HIF-1α and COX-2 were 35.0% (21/60) and 38.3% (23/60) respectively. High level expression of HIF-1α was significantly correlated with clinical stages(X2=4.331, P<0.05) and lymph nodes metastases(Fisher's exact test, P<0.05). High level expression of COX-2 was significantly correlated with clinical stage (X2=8.539, P<0.01) and T stages (X2=6.792, P<0.01). With univariate analysis, high level expressions of HIF-1α and COX-2 were significantly associated with a worse overall survival (X2=6.003, P<0.05 and X2=9.489, P<0.01, respectively) and disease-free survival(X2=5.010,P<0.05 and X2=6.102,P<0.05, respectively). With multivariate analysis, recurrence and high level expression of COX-2 were two unfavorable prognostic factors (RR=7.104, P=0.003; RR=5.714, P=0.008). Conclusions The expressions of HIF-1α and COX-2 played an important role in the process of tumorigenesis and development of LSCC, The expression of HIF-1α was correlated with COX-2 in LSCC. COX-2 and recurrence were probably significant risk factors for prognosis of LSCC.