【作者】 黄莉；

【导师】 杨新明；

【作者基本信息】 中南大学 ， 耳鼻咽喉科学， 2008， 硕士

【摘要】 喉癌是头颈部的常见的恶性肿瘤,其发病率逐年上升,发病机制不甚明确。从基因水平探索肿瘤的发生、发展、转移及治疗是目前研究的热点。程序性细胞死亡(PCD)是受基因控制的细胞死亡方式。目前,人们对程序性死亡的研究主要集中在两大类:由caspase介导的细胞凋亡(1型细胞死亡)和非caspase介导的白体吞噬(2型细胞死亡)。细胞进行自体吞噬时,细胞质中的线粒体等细胞器首先被称为“隔离膜”的囊泡所包被,然后被运送到溶酶体/空泡中降解。研究表明自体吞噬能抑制肿瘤细胞生长。Beclin 1与Bcl-2家族有关,其位于染色体17q21,是自噬重要的正调节因子。有文献报道染色体17q21的等位基因缺失在卵巢癌中高达75%,乳腺癌为50%,前列腺癌中为40%。研究表明Beclin 1杂合性缺失是细胞发生恶性转化的原因之一,是一个候选的肿瘤抑制基因。目的:本实验的目的是探讨Beclin 1在喉鳞状细胞癌中的表达及与临床分期、肿瘤发生部位、病理分级和淋巴结转移等特征之间的关系。方法:应用免疫组织化学SP法,检测Beclin 1在38例喉癌及20例癌旁组织标本中的表达.利用SPSS统计学软件及X~2检验分析其与各临床病理参数之间的关系。结果1.Beclin 1在喉鳞状细胞癌组织和癌旁组织中的表达率分别为28.95%(11/38)和70%(14/20),癌组织中的表达率明显低于癌旁组织,两组间有显著差异(p＜0.01)。2.Beclin 1在高分化鳞癌组织中的表达率为35%(7/20),在中低分化鳞癌中的表达率为22.22%(4/18),两组之间的差异无显著性(p＞0.05)。3.有淋巴结转移的癌组织和无淋巴结转移的癌组织中的Beclin 1的表达率分别为12.5%(2/16)和40.9%(9/22),两组有显著差异(p＜0.05)。4.临床分期Ⅰ-Ⅱ期喉癌组织中Beclin 1的表达率为40%(6/15),而在Ⅲ-Ⅳ期喉癌组织中为21.74%(5/23)两者之间比较无显著性差异(p＞0.05)。5.Beclin 1在声门上型喉癌组织中的表达率为23.08%(3/13),在声门型喉癌组织中表达率为32%(8/25),两者之间的差异无显著性(p＞0.05)。结论:研究表明Beclin 1在喉鳞状细胞癌中的表达明显低于癌旁组织,在有淋巴结转移的喉癌组织中Beclin 1的表达明显低于无淋巴结转移组织。说明Beclin 1的表达异常与喉鳞癌的发生和转移有关。更多还原

【Abstract】 Laryngeal carcinoma is one of most common malignant neoplasm in head and neck.In recent years,the morbidity of laryngocarcinoma appears an increasing tendency.It has become special focus to investigate the oncogensis,developing,metastasis and management of the tumor from the molecule level.Programmed cell death(PCD)is an essential and highly orchestrated process.Two major types of PCD have been distinguished:the caspase-mediated process of apoptosis(type 1 cell death)and the caspase-independent process involving autophagy(type 2 cell death). Autophagy is an evolutionary conserved lysosomal pathway involved in the turnover of long lived proteins and organelles.Autophagy starts with the formation of a multilayer membrane-bound autophagosome that sequesters fractions of the cytoplasm.Autophagy has increased inhibition of tumor cell growth,in a variety of tumor cell lines in the low-level expression.Beclin 1,identified as a Bcl-2 interacting protein,is known to enhance autophagy.The human beclin-1 gene has been mapped to a region of chromosome 17q21 that is monoallelically deleted in up to 75% of ovarian cancers,50%of breast cancers,and 40%of prostate cancers. Based on these observations,it demonstratethat Beclin 1 is a novel mechanism of cell-growth control and tumor suppression.Beclin-1 is a candidate tumor-suppressor gene.Objective:The aim of this investigation is to study the expression of Beclin-1 in laryngeal squamous cell carcinoma and normal tissues adjacent to cancer,and study the correlation between its expression and clinical-pathological parameters of primary laryngeal squamous cell carcinoma.Methods:Expression level of Beclin 1 was detected in 38 human laryngeal cancer samples and 20 normal tissues adjacent to cancer respectively,and their correlation with tumor sit,tumor grade,lymph node metastasis and clinical stage was studied by immunohistochemistry(IHC)methods.The statistical evaluation was performed with SPSS software for windows.Results:1.The expression of Beclin 1 in LSCC are obviously lower than that in normal tissues adjacent to cancer and there was statistical significance(P＜0.01).2.The positive rate of Beclin 1 in well-differentiated samples and poorly differentiated samples were 35%(7/20)and 22.22%(4/18) respectively,there was no statistical significance(P＞0.05). 3.The expression of Beclin 1 in LSCC with lymph node metastasis were obviously lower than that without,and there was statistical significance(P＜0.05).4.The positive rate of Beclin 1 inⅠ-Ⅱstages andⅢ-Ⅳstages were 40%(6/15)and 21.74%(5/23)respectively,there was no statistical significance(P＞0.05).5.The positive rate of Beclin 1 in supra-glottic carcinoma and glottic carcinoma were 23.08%(3/13)and 32%(8/25)respectively.There was no statistical significance(P＞0.05).Conclusion:The expression of Beclin-1 in LSCC are obviously lower than that in normal tissues adjacent to cancer and the expression of Beclin 1 in LSCC with lymph node metastasis were obviously lower than that without,which showed Beclin-1 had a close relationship with LSCC and its metastasis.The study of relationship between Beclin 1 and laryngeal carcinoma reminds us a new gene therapy of laryngeal carcinoma by strengthen the function of Beclin 1.更多还原