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PTEN和IGF-1R在喉鳞癌中的相关研究及临床意义

Relationship Study and Clinical Signification of PTEN and IGF-1R in Laryngeal Squamous Cell Carcinoma and Polyps of Vocal Cord

【作者】 牛传贵

【导师】 高建中;

【作者基本信息】 宁夏医科大学 , 耳鼻咽喉科学, 2009, 硕士

【摘要】 目的本研究应用免疫组化SP的方法检测了喉鳞状细胞癌中PTEN和IGF-1R蛋白的表达情况,并分析它们与喉鳞状细胞癌临床生物学特性的关系,探讨它们与喉鳞状细胞癌中发生、发展的关系,为临床对该病的诊断、治疗估计提供理论参考与帮助。方法取喉部鳞状细胞癌(LSCC)石蜡标本50例作为研究对象,所有病例临床数据完整,术前未经化疗、放疗等,术后经病理确诊为喉鳞癌。另取30例声带息肉(VCP)粘膜标本作为对照组。采用免疫组织化学SP法测定PTEN和IGF-1R的表达,分析PTEN和IGF-1R的表达与喉鳞癌的组织学分化程度、T分级、临床分期及淋巴结转移等的关系。统计学分析应用统计软件SPSS13.0进行分析。P﹥0.05认为差异无统计学意义,P<0.05认为差异有统计学意义,P<0.01认为差异有显著统计学意义。结果PTEN蛋白在喉鳞状细胞癌、声带息肉表达阳性表达率分别为58%和96.7%,两者比较差异有显著统计学意义(P<0.01)。PTEN蛋白在不同病理分级的喉鳞癌中阳性表达率不同,高分化、中分化、低分化阳性表达率分别为75.00%、63.64%、25.00%,三者比较差异有显著统计学意义(P﹤0.01)。在喉鳞状细胞癌患者T分期T1、T2、T3、T4期阳性表达率分别为91.67%、75.00%、30.43%、66.67%,差异有显著统计学意义(P﹤0.01)。在喉鳞状细胞癌患者临床分期I期、II期、III期、IV期阳性表达率为91.67%、80.00%、35.00%、37.50%,差异有显著统计学意义(P﹤0.01)。有淋巴结转移者PTEN蛋白阳性表达率为33.33%,无淋巴结转移者PTEN蛋白阳性表达率为65.79%,两者比较差异有统计学意义(P﹤0.05)。PTEN蛋白在不同年龄,不同性别,不同肿瘤部位差异无统计学意义。随T分期、临床分期的增加、分化程度降低及淋巴结转移,PTEN阳性表达率基本逐渐降低。IGF-1R蛋白在喉鳞状细胞癌、声带息肉表达阳性表达率分别为68.00%和16.70%,两者比较差异有显著统计学意义(P<0.01)。IGF-1R蛋白在不同病理分级的喉鳞癌中阳性表达率不同,高分化、中分化、低分化阳性表达率分别为43.75%、72.73%、91.67%,三者比较差异有显著统计学意义(P﹤0.01)。在喉鳞状细胞癌患者T分期T1、T2、T3、T4期阳性表达率分别为33.33%、58.33%、86.96%、100.00%,差异有统计学意义(P﹤0.05)。在喉鳞状细胞癌患者临床分期I期、II期、III期、IV期阳性表达率为33.33%、50.00%、85.00%、100.00%,差异有显著统计学意义(P﹤0.01)。淋巴结转移者IGF-1R蛋白阳性表达率为100.00%,无淋巴结转移者IGF-1R蛋白阳性表达率为57.89%,两者比较差异显著,P﹤0.01,有统计学意义。IGF-1R蛋白在不同年龄,不同性别,不同肿瘤部位差异无统计学意义。随T分期、临床分期的增加、分化程度降低及淋巴结转移,IGF-1R阳性表达率逐渐增高。PTEN表达阳性的病例中,IGF-1R表达阳性率为51.72%;PTEN表达阴性的病例中,IGF-1R表达阳性率为90.47%。IGF-1R表达阳性的病例中, PTEN表达阳性率为44.11%;IGF-1R表达阴性的病例中, PTEN表达阳性率为87.50%。经Spearman等级相关分析, r= -0.570 ,P=0.000。PTEN表达与IGF-1R表达明显负相关。结论1、喉鳞癌组织中PTEN蛋白表达降低,IGF-1R蛋白表达增高,PTEN缺失和/或蛋白的失活和IGF-1R蛋白的高表达可能在喉鳞癌中起作用。2、PTEN和IGF-1R蛋白表达同喉鳞癌的分化程度、临床分期和淋巴结转移明显相关,PTEN和IGF-1R蛋白表达可能在喉鳞癌的发生发展及侵袭进展中起作用,两者的表达水平可能可作为判断肿瘤恶性程度的标志。推测PTEN缺失和/或失活可能是喉鳞癌的发病机制之一,IGF-1R的过度表达也可能是喉鳞癌的发病机制之一。3、喉鳞癌组织中PTEN蛋白低表达,IGF-1R蛋白高表达,并且呈负相关,推测在喉鳞癌中PTEN与IGF-1R两者之间失衡,并且可能在喉鳞癌中起作用。

【Abstract】 Objective This study is to detect the expression of PTEN protein and IGF-1R protein in the Laryngeal squamous cell carcinoma(LSCC)and Polyps of vocal cord (VCP) by S-P Immunohistochemistry methods, and to analyze the relations with LSCC’biology characteristics, and to investigate the relations with occurrence and development of LSCC, so that provide theoretical reference and help to its diagnosis and therapy. Methods To take 50 pieces of petroline samples of Laryngeal squamous cell carcinoma as study object, all cases of disease content of integrity clinical data , preoperative patient were not undergo chemotherapy and/or radiotherapy and so on. After-operative samples were final diagnosis as LSCC by pathological-diagnosis. At the same time, to take 30 pieces of VCP mucosae samples as control group. To detect the expression of PTEN protein and IGF-1R protein in LSCC and VCP by S-P Immunohistochemistry methods, to analyze the relations with histology differentiated degree, T grade, clinical stage and lymph node diversion of LSCC. Statistic analyses were done by SPSS 13.0 software. P﹥0.05 was to consider there are not significant difference statistically. P<0.05 was to consider there are significant difference statistically. P<0.01 was to consider there are notable significant difference statistically. Results The positive rates of PTEN were respectively 58%, 96.7% in LSCC,and VCP, there were notable significant difference between them statistically(P﹤0.01). The positive rates were respectively 75.00%、63.64%、25.00% in well-differentiated, moderately differentiated and poorly differentiated. there were notable significant difference among them statistically(P﹤0.01). The positive rates were respectively 91.67%, 75.00%, 30.43%, 66.67% in T1 grade, T2 grade, T3 grade and T4 grade. There were notable significant difference among them statistically(P﹤0.01).The positive rates were respectively 91.67%、80.00%、35.00%、37.50% in I stage, II stage, III stage and IV stage. There were notable significant difference among them statistically(P﹤0.01).The positive rates were respectively 33.33%, 65.79% in have and without lymph node diversion, there were significant difference between them statistically(P﹤0.05),there are not significant difference statistically among different age, sex, tumour position. With increasing of T grade, clinical stage and lymph node diversion, the positive rates of PTEN were basically gradually cutting down. With cutting down of histology differentiated degree, the positive rates of PTEN were basically gradually cutting down.The positive rates of IGF-1R were respectively 68%, 16.70% in LSCC,and VCP, there were notable significant difference between them statistically (P﹤0.01). The positive rates were respectively 43.75%, 72.73%, 91.67% in well-differentiated, moderately differentiated and poorly differentiated. there were notable significant difference among them statistically (P﹤0.01). The positive rates were respectively 33.33%、58.33%、86.96%、100.00% in T1 grade, T2 grade, T3 grade and T4 grade. There were notable significant difference among them statistically(P﹤0.01), The positive rates were respectively 33.33%、50.00%、85.00%、100.00% in I stage, II stage , III stage and IV stage. there were notable significant difference among them statistically(P﹤0.01).The positive rates were respectively 100%, 57.89% in have and without lymph node diversion, there were notable significant difference between them statistically(P﹤0.01)there are not significant difference statistically among different age, sex, tumour position.With increasing of T grade, clinical stage and lymph node diversion, the positive rates of IGF-1R were basically gradually increasing. With cutting down of histology differentiated degree, the positive rates of IGF-1R were basically gradually increasing. The positive rates of IGF-1R were 51.72% in the cases of PTEN positive expression, the positive rates of IGF-1R were 90.47% in the cases of PTEN negative expression; the positive rates of PTEN were 44.11% in the cases of IGF-1R positive expression, the positive rates of PTEN were 87.50% in the cases IGF-1R of positive expression. Through rank correlation analysis, r= -0.570 ,P=0.000. PTEN expression was obviously negative correlation with IGF-1R expression. Conclusions 1. The expression of PTEN protein is cutting down, the expression of IGF-1R protein is increasing , absence and/or deactivation of PTEN and overexpression of IGF-1R are probably playing a role in LSCC. 2. The expression of PTEN protein and IGF-1R protein are correlated with histology differentiated degree, T grade, clinical stage and lymph node diversion of LSCC. PTEN and IGF-1R probably play a role in occurrence, development, invasion and progress of LSCC, and their expression-level probably become mark to judge tumour’s malignant-degree. We can draw a conclusion that absence and/or deactivation of PTEN and overexpression of IGF-1R are probably section of disease mechanism. 3. The study show that PTEN protein is low-expression, IGF-1R protein is overexpression, and they are negative correlation, so we can infer that there is disequilibrium between PTEN and IGF-1R, and this disequilibrium probably play a role in LSCC.

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