喉鳞状细胞癌发生过程中Bak和Bcl-xl基因蛋白的参与 排除与性别和吸烟关系

Expression of Bak and Bcl-xl in the development of laryngeal squamous cell carcinoma:Excluding the relation with gender and smoking

目的:探讨促凋亡基因Bak和凋亡抑制基因Bcl-xl在喉鳞状细胞癌中的表达,及其与喉癌发生和预后的关系。方法:取哈尔滨医科大学附属二院耳鼻咽喉-头颈外科2000-07/2002-04行手术切除的45块喉原发性喉鳞癌及25块正常喉黏膜石蜡标本。检测标本组织中Bak和Bcl-xl蛋白的表达,采用免疫组织化学染色方法分析患者性别、吸烟情况、临床分期及不同肿瘤病理分级和淋巴结转移与喉癌组织中Bak和Bcl-xl蛋白表达的关系。结果:①正常喉黏膜Bak阳性表达:显著高于原发性喉鳞癌犤92%(23/25),44%(20/45),P<0.01犦。②正常喉黏膜Bcl-xl阳性表达:显著低于原发性喉鳞癌犤16%(4/25),53%(24/45),P<0.01犦。③喉癌组织中Bak和Bcl-xl蛋白的表达:与患者的性别、吸烟情况及临床分期无关(P>0.05),而与肿瘤病理分级和淋巴结转移显著相关(P<0.005,P<0.01)。结论:Bak在喉鳞癌中表达较正常喉黏膜明显减少,其表达下调与喉癌的发生密切相关。肿瘤分化越好,Bcl-xl的表达越强。Bak和Bcl-xl蛋白的表达与肿瘤病理分级和淋巴结转移显著相关,说明Bak蛋白表达对防止癌细胞转移、扩散具有积极意义,可作为对喉鳞癌预后判断的指标。

AIM：To investigate the expression of Bak promoting the apoptosis and Bcl-xl inhibiting the apoptosis in laryngeal squamous cell carcinoma and to elucidate the relation of the expression of them to the pathogenesis and prognosis of carcinoma of larynx. METHODS：Totally 45 sections of primary laryngeal squamous cell carcinoma and 25 normal laryngeal tissues embedded with paraffin were selected from July 2000 to April 2002 in the Department of Otolaryngology-Head and Neck Surgery,Second Affiliated Hospital of Harbin Medical University. The expression of Bak and Bcl-xl protein in the sample tissue was detected.Immunohistochemisty was used to analyze the gender,smoking condition, clinical stage as well as the relation of pathological grading of different tumors,lymph node metastasis and the expression of Bak and Bcl-xl protein in carcinoma of larynx. RESULTS： ①Bak positive expression rate of normal laryngeal mucous membrane was higher significantly than that of primary laryngeal squamous cell carcinoma[92% （23/25） ,44%（20/45 ） ,P 〈 0.01].②Bcl-xl positive expression rate of normal laryngeal mucous membrane was lower significantly than that of primary laryngeal squamous cell carcinoma [16%（4/25）,53% （24/45） ,P 〈 0.01].③The expression of Bak and Bcl-xl protein in the tissue of carcinoma of larynx was not related with the gender,smoking condition and clinical stage （P 〉 0.05）,but was related significantly with pathological grading of tumors and lymph node metastasis（P 〈 0.O05,P 〈 0.01）. CONCLUSION：The expression of Bak in laryngeal squamous cell carcinoma was decreased significantly than that in the normal laryngeal mucous membrane and its down-regulated expression was correlated closely with the occurrence of carcinoma of larynx.The better the tumor differentiates,the stronger the expression of Bcl-xl is.The expression of Bak and Bcl-xl protein was correlated significantly with pathological grading of tumors and lymph node metastasis,suggesting that the expression of Bak protein has active meaning in preventing the metastasis and diffusion of neoplastic cell and their expression may provide evidence for the evaluation of prognosis of laryngeal squamous cell carcinoma.