整合素连接激酶mRNA的表达与喉鳞状细胞癌相关性研究

目的:探讨整合素连接激酶(ILK)与喉鳞状细胞癌(LSCC)发生、发展的关系。方法:应用RT-PCR方法,检测64例LSCC标本(LSCC组)和10例正常喉黏膜组织(对照组)中ILK mRNA的表达。结果:LSCC组ILK mRNA表达(0.644±0.098)明显高于对照组(0.032±0.026),差异有统计学意义(P<0.05);ILK mRNA在有淋巴结转移组织中的表达(0.867±0.247)明显高于无淋巴结转移组织(0.389±0.199),差异有统计学意义(P<0.05)。随着LSCC临床T分期的发展,ILK mRNA的表达均相应升高,但相邻两组间差异无统计学意义(均P>0.05)。结论:ILK的高表达对LSCC的形成和发展起重要作用;ILK mRNA高表达与LSCC淋巴结转移密切相关,提示ILK可能成为预测LSCC转移和预后的生物学指标。     

喉癌p53基因异常的临床意义

目的p53基因异常是恶性肿瘤发生发展中常见的现象,但其临床意义仍存在争议。回顾性研究喉癌p53蛋白过度表达,并分析其与临床病理特征和致癌危险因素之间的关系,以探求p53基因异常可能的致病机制和预后判断方面的意义。 方法 以100例手术切除的喉癌标本为研究对象,收集并记录诊断时的临床参数和致癌危险因素,用免疫组化法检测p53蛋白表达。 结果100例喉癌标本中p53蛋白的阳性表达率为66％;检测中发现p53蛋白表达与年龄、性别、饮酒程度、肿瘤部位、临床分期和病理分级等临床病理参数之间无关联(P>0.05)。 结论p53基因异常与喉癌的发生发展有关,与喉癌预后无关。     

喉鳞状细胞癌中微卫星的异常改变

目的：从分子生物学水平探究微卫星的不稳定性（MSI）与杂合性缺失（LOH）在喉鳞状细胞癌发病机制中的意义。方法：选择3号,5号及11号染色体的3个微卫星位点采用PCR和聚丙烯酰胺凝胶电泳-硝酸银染色方法对40例喉鳞状细胞癌患者手术切除的癌组织及癌旁正常组织进行微卫星分析。结果：40例喉鳞状细胞癌中,35例（87．5％）分别有1～3个微卫星位点发生MSI或LOH。微卫星异常改变发生率最高的位点为D5s592,占70％（28／40）;其次是D3s1228位点,占52．5％（21／40）。结论：在3p14区域及5q23区域附近的抑癌基因参与致癌机制,D3s1228和D5s592的微卫星改变与喉鳞状细胞癌的临床分期相关。     

Expression of protein p27 is associated with progression and prognosis in laryngeal cancer.

OBJECTIVE: A cyclin-dependent kinase inhibitor, p27kip1, is recognized as a negative regulator of the cell cycle. To clarify whether immunohistochemical detection of p27 might provide prognostic information, we investigated the expression of p27 in laryngeal squamous cell carcinoma (SCC). STUDY DESIGN: A retrospective study of patients was performed in 109 cases of laryngeal SCC. In addition, we investigated the expression of p53 and granulocyte colony-stimulating factor receptor (GCSF-R) to examine the prognostic significance of them in the same samples. METHODS: Immunohistochemical staining by specific monoclonal antibodies was performed using the avidin-biotin-peroxidase complex technique. RESULTS: Advanced tumor size and clinical stage and the occurrence of lymph node metastasis were associated with the absence of p27 expression, but not correlated with p53 expression and GCSF-R expression. The overall 5-year survival rate in the p27-positive group was significantly higher than that in the p27-negative group. In the Cox proportional hazard model, p27 was demonstrated to be the most powerful prognostic factor among gender, tumor size, lymph node metastasis, stage of disease, and p53 and GCSF-R expression. CONCLUSIONS: We concluded that assessment of p27 expression is useful as a prognostic factor for laryngeal SCC and of value in selecting patients with laryngeal SCC for aggressive therapy.     

p63 and Ki-67 immunostainings in laryngeal squamous cell carcinoma are related to survival

To examine the prognostic significance of the immunohistochemical expression of p63 and Ki-67 oncoproteins in patients with laryngeal squamous cell carcinoma, a retrospective evaluation was carried out on a cohort of 108 patients with primary laryngeal squamous cell carcinoma (LSCC) treated by primary surgery. For the immunohistochemical evaluation, tissue section obtained by formalin-fixed and paraffin-embedded tissue blocks from resection of each patient was used. Clinicopathologic data were associated with the immunostaining results. The association among the considered variables was assessed by Fisher’s exact test, Mann–Whitney test, non-parametric χ ² test, and Spearman’s rho rank test was used to assess the relations among them. Differences in p63 and Ki-67 immunoreactivity among the different groups were compared via Kruskal–Wallis test and post hoc tests were performed using Mann–Whitney test with Bonferroni correction. The overall survival rate was estimated via Kaplan–Meier method, and the cumulative incidence functions for different groups were compared using log-rank statistics. Cox proportional hazard model was employed in a multivariate analysis to assess the effect of prognostic factors in the overall survival rate. Furthermore, taking into account death due to other causes, we estimated LSCC-related survival and disease-free survival rates using competing risk analysis. The results of immunohistochemical examination showed a statistically significant relationship between the up-regulation of P63 and Ki-67, an increase in histological grading, and primary tumours associated with lymph node metastases. p63 and Ki-67 up-regulation was related to a shorter disease-free survival and a significant association was found between p63 and Ki-67 percentage of positive cells and patient survival. Finally, we noticed a significant relation between p63 and Ki-67 (ρ = 0.87). On the other hand, no statistically significant associations were found between p63 and Ki-67 down-regulation and clinicopathologic data. Our findings suggest that abnormal p63 and Ki-67 immunoreactivity may be involved in the early phases of laryngeal tumorigenesis and may become a significant prognostic predictor for both overall and disease-free survivals. These biomarkers could thus help in the selection of high-risk patients with LSCC who may benefit from more aggressive therapy or chemoprevention.     

p73和PCNA的表达与喉鳞状细胞癌的预后

目的：探讨喉鳞状细胞癌（LSCC）中p73、增殖细胞核抗原（PCNA）基因的表达与患者临床、病理参数和预后的关系。方法：采用免疫组织化学SABC技术检测65例LSCC组织及23例癌旁组织中p73、PCNA基因的表达情况。结果：p73、PCNA蛋自在65例LSCC组织中的表达水平较23例癌旁组织明显增强（均P〈0．05）。65例LSCC组织中,p73蛋自在TNM分期Ⅲ～Ⅳ期、远处转移及复发患者中的表达水平较Ⅰ～Ⅱ期、无转移及初发患者表达增强（P〈O．05）。PCNA蛋自在TNM分期Ⅲ～Ⅳ期患者、低分化癌、复发患者和有颈淋巴结转移及远处转移患者中的表达水平较Ⅰ～Ⅱ期、高中分化、初发患者和无转移患者中的表达增强（P〈O,05）。PCNA蛋白的表达与患者预后明显相关。经Cox比例风险模型进行分析,PCNA表达是患者预后不良的重要指标（其相对危险度RR=2.43,P〈0．05）。LSCC组织中p73、PCNA的基因表达存在正相关性（P〈0、05）。结论：p73蛋自在LSCC的发生、发展过程中可能扮演了癌基因的角色。PCNA蛋白的表达与LSCC的危险性存在密切关系,可作为判断LSCC患者预后的重要指标。LSCC中p73、PCNA的表达存在正相关关系。     

p27蛋白和增殖细胞核抗原在上颌窦鳞癌中的表达

目的探讨p27蛋白和增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)在上颌窦鳞癌中的表达及其与上颌窦鳞癌发生发展的关系.方法应用免疫组化SABC法检测35例上颌窦鳞癌和15例鼻腔鼻窦内翻性乳头状瘤的p27蛋白和PCNA表达.结果p27蛋白及PCNA染色阳性细胞均为细胞核着色.其中上颌窦鳞癌的p27蛋白阳性率为25.71%,鼻腔鼻窦内翻性乳头状瘤的阳性率为73.3%.二者差异有高度显著性(P＜0.01).但鳞癌各组间经统计学检验差异无显著性.上颌窦鳞癌PCNA指数为86.94±9.83,鼻腔鼻窦内翻性乳头状瘤的PCNA指数为46.14±2.66,二者差异有高度显著性(P＜0.001).随上颌窦鳞癌分化程度的降低,PCNA指数增加,不同分化间PCNA指数差异有显著性(P＜0.05).结论检测上颌窦鳞癌组织中p27蛋白和PCNA的表达能够快速、准确地反映肿瘤细胞的增殖状态和评价预后,对判定上颌窦鳞癌的恶性程度及指导治疗有一定的意义.     

喉鳞状细胞癌中Skp2和p27蛋白的表达

目的 探讨细胞S相激酶相关蛋白(S-phase kinase associated protein 2,Skp2)、p27蛋白与喉鳞状细胞癌(简称喉癌)各临床因素及预后的相关性.方法 采用免疫组化SP法检测79例喉癌患者肿瘤组织的Skp2、p27表达.结果 喉癌中Skp2高表达率(53.16%)显著高于正常喉组织(0%,P＜0.05);喉癌Skp2蛋白低表达组的5年生存率(72.18%)显著高于高表达组(44.17%,P＜0.01).p27蛋白在喉癌和癌旁喉组织中的高表达率分别为30.38%和90%,差异具有显著性(P＜0.05);喉癌p27蛋白高表达组的5年生存率(72.98%)显著高于低表达组(51.13%,P＜0.01).将Skp2和p27结合分析,Skp2高表达并p27低表达组的5年生存率最低,与另一组相比具有显著性差异(P=0.001).结论 Skp2蛋白通过降解靶蛋白p27可能在喉癌发生、发展中发挥重要作用.     

Jab1和p27kip1蛋白在喉鳞状细胞癌中的表达

目的 探讨Jun激活区域-连接蛋白1(c-Jun activation domain-binding p rotein 1,Jab1)和p27kip1的表达与喉鳞状细胞癌(laryngeal squamous cell carcinomas,LSCC)发生、发展的关系及两种蛋白之间的相关性.方法 免疫组织化学SP法检测23例正常喉黏膜(normal laryngeal tissues,NLT)和68例LSCC组织中Jab1和p27kip1的表达.结果 NLT和LSCC组织中,Jab1和p27kip1蛋白阳性表达率差异均有显著性(P＜0.01).LSCC中Jab1的过表达与临床分期及颈淋巴结转移显著相关(P＜0.05),p27kip1的表达与颈淋巴结转移显著相关(P＜0.05),Jab1的表达与p27kip1的表达呈负相关(P＜0.05).生存率分析表明,Jab1的过表达与患者的总生存率呈负相关(P＜0.05).结论 Jab1可能通过对周期素依赖性蛋白激酶抑制因子(cell cycle inhibitory protein,CKI)p27kip1蛋白的降解而参与LSCC的发生、发展,联合检测Jab1及p27kip1蛋白的表达有助于综合评估LSCC的生物学行为及预后.     

Over-expression of tumour suppressor gene p53 in laryngeal squamous cell carcinomas and its prognostic significance

p53 is a nuclear phosphoprotein which acts as a tumour suppressor factor, regulating cell growth and division. Mutations in the p53 gene appear to be the most common genetic alterations in human cancer. The aim of this study was to investigate p53 expression in laryngeal squamous cell carcinomas and to assess its role as a marker of prognostic significance. Using immunohistochemical staining techniques, a series of laryngeal carcinomas (n= 87) were examined for expression of the mutant form of p53 phosphoprotein using the monoclonal antibody PAB 1801. p53 over-expression was noted in 50 biopsies of laryngeal carcinomas (57.5%) but not in any of the non-neoplastic laryngeal mucosa which were used as the control. There was no statistical correlation between p53 immunoreactivity and the clinicopathological parameters of the cancers including: site of tumour, TNM staging, differentiation grading and tumour recurrence. These findings indicate that p53 expression is strongly associated with carcinoma cells and not with normal cells in the larynx. However, p53 expression is probably unrelated to the biological aggressiveness of these tumours.     

Loss of p21 expression is associated with p53 mutations and increased cell proliferation and p27 expression is associated with apoptosis in maxillary sinus squamous cell carcinoma

CONCLUSIONS: Loss of p21 expression dependent on the p53 mutation may be associated with higher tumor cell proliferation, and low p27 expression may be associated with decreased spontaneous apoptosis, resulting in poorer prognosis in patients with maxillary sinus squamous cell carcinoma (SCC). OBJECTIVE: We have previously reported that p53 mutations and decreased spontaneous apoptosis were associated with poor prognosis in maxillary sinus SCC. However, whether p21 and p27 expression and cell proliferation correlate with either p53 status, spontaneous apoptosis or prognosis in maxillary sinus SCC has not been evaluated. MATERIAL AND METHODS: Seventy patients with maxillary sinus SCC were analyzed. Tumor biopsy specimens were examined for p21 and p27 expression using an immunohistological method. The percentage of proliferating cells labeled by anti-Ki-67 mAb was expressed as the Ki-67 index (KI). RESULTS: Loss of p21 expression correlated with p53 mutations (p=0.0072). The KIs in patients without p21 expression and with p53 mutations were significantly higher than those in patients with p21 expression (p=0.0119) and those without p53 mutations (p=0.0048). Patients with p27 expression showed a significantly higher apoptotic index than those without (p=0.0012). Kaplan-Meier analysis showed that p21 expression was closely associated with prolonged disease-free survival in the group with a normal p53 status (p=0.0472). Multivariate analysis identified high KI as an independent prognostic marker (p=0.047).     

Loss of p21 expression is associated with p53 mutations and increased cell proliferation and p27 expression is associated with apoptosis in maxillary sinus squamous cell carcinoma

Conclusions. Loss of p21 expression dependent on the p53 mutation may be associated with higher tumor cell proliferation, and low p27 expression may be associated with decreased spontaneous apoptosis, resulting in poorer prognosis in patients with maxillary sinus squamous cell carcinoma (SCC). Objective. We have previously reported that p53 mutations and decreased spontaneous apoptosis were associated with poor prognosis in maxillary sinus SCC. However, whether p21 and p27 expression and cell proliferation correlate with either p53 status, spontaneous apoptosis or prognosis in maxillary sinus SCC has not been evaluated. Material and methods. Seventy patients with maxillary sinus SCC were analyzed. Tumor biopsy specimens were examined for p21 and p27 expression using an immunohistological method. The percentage of proliferating cells labeled by anti-Ki-67 mAb was expressed as the Ki-67 index (KI). Results. Loss of p21 expression correlated with p53 mutations (p=0.0072). The KIs in patients without p21 expression and with p53 mutations were significantly higher than those in patients with p21 expression (p=0.0119) and those without p53 mutations (p=0.0048). Patients with p27 expression showed a significantly higher apoptotic index than those without (p=0.0012). Kaplan–Meier analysis showed that p21 expression was closely associated with prolonged disease-free survival in the group with a normal p53 status (p=0.0472). Multivariate analysis identified high KI as an independent prognostic marker (p=0.047).     

Skp2、p27蛋白在喉鳞状细胞癌中的表达及意义

目的:探讨喉鳞状细胞癌(LSCC)中Skp2和p27蛋白的表达与患者临床病理和预后的关系以及两种蛋白之间的相关性。方法:用免疫组织化学SP法检测20例正常喉黏膜(NLT)、27例LSCC癌前病变不典型增生(LPL)和70例LSCC组织中Skp2和p27蛋白的表达情况。结果:Skp2蛋白在NLT、LPL和LSCC中的阳性表达率分别为10.00%(2/20),37.04%(10/27)和41.43%(29/70),后两者的阳性率显著高于前者(均P<0.05)。Skp2蛋白表达与临床分期及淋巴结转移显著正相关(P<0.05)。p27蛋白在NLT和LSCC中阳性率分别为85.00%(17/20),48.57%(34/70),两者比较,差异有统计学意义(P<0.01)。p27蛋白表达与颈淋巴结转移呈负相关(P<0.05)。Skp2蛋白在LSCC中表达与p27蛋白呈负相关(P<0.05)。Skp2表达阳性而p27表达阴性的LSCC患者生存率明显低于其他患者(P<0.05)。结论:Skp2可能通过对细胞周期抑制因子p27蛋白的降解而参与LSCC的发生、发展,联合检测Skp2及p27蛋白的表达对预测LSCC患者的预后具有重要意义。     

喉鳞状细胞癌中细胞周期蛋白E和p27异常表达的临床意义

目的：探讨喉鳞状细胞癌（LSCC）中细胞周期蛋白E（CyclinE）和p27蛋白的表达情况及其临床意义,旨在寻找影响LSCC患者预后的新指标。方法：采用免疫组织化学ElivisionTM法检测160例LSCC和20例正常喉黏膜组织（NLT）中CyclinE和p27的表达情况;统计分析CyclinE和p27蛋白之间及其二者与LSCC患者临床病理因素和总体生存期之间的关系。结果：LSCC组织中CyclinE和p27阳性率分别为62．50％（100／160）和41．25％（66／160）,NLT中CyclinE和p27阳性率分别为35％（7／20）和70％（14／20）（P〈0．05）;CyclinE和p27与LSCC患者淋巴结转移和PTNM分期有关（P〈0．05）,与年龄、性别及肿瘤直径、部位和分化程度无关（P〉0．05）;CyclinE和p27呈显著负相关,r=-0．767（P％0．05）;Cox多因素分析显示淋巴结转移、PTNM分期、CyclinE和p27是影响LSCC患者预后的独立危险因素。Kaplan-Meier生存分析显示LSCC患者的总体生存率为36．9％（P〈0．05）;CyclinE阳性组患者5年生存率为8％,阴性组为80％（P〈O．05）;而p27蛋白阳性组患者5年生存率为77．27％,阴性组为5．32％（P〈O．05）。结论：CyclinE基因的激活同时伴有p27基因的失活可能是LSCC发生发展和侵袭转移的分子基础,联合检测CyclinE和p27对判断LSCC患者预后有重要意义。     

程序性细胞死亡因子4蛋白表达与喉鳞状细胞癌相关性研究

目的:探讨程序性细胞死亡因子4(PDCD4)与喉鳞状细胞癌发生和发展的关系.方法:免疫组织化学方法和Western印迹法检测喉鳞状细胞癌组织及癌旁正常喉黏膜组织中PDCD4蛋白表达.结果:免疫组织化学染色显示喉鳞状细胞癌组织中PDCD4蛋白阳性表达率低于癌旁正常喉黏膜组织,差异有统计学意义(P＜0.01).喉鳞状细胞癌组织中PDCD4蛋白阳性表达和患者的年龄、性别、临床分型(肿瘤部位)、TNM分期无相关性,与病理分级、淋巴结转移有显著相关性.免疫印迹结果亦显示喉鳞状细胞癌组织中PDCD4蛋白表达低于癌旁正常喉黏膜组织(P＜0.01).结论:PDCD4蛋白低表达与喉鳞状细胞癌的发生和发展有关,PDCD4可能成为预测喉鳞状细胞癌转移和预后的生物学指标.     

喉鳞状细胞癌染色体端粒缺失与细胞分裂后期染色体桥现象

喉鳞状细胞癌（简称鳞癌）常表现为大量、复杂的染色体变化，但其潜在的机制目前尚不完全清楚。细胞遗传学研究提出染色体异常的融合和断裂是促进染色体不稳定性的重要机制之一。这种现象大体表现为细胞分裂后期的异常形态-染色体桥。另外，端粒是人类染色体末端一组TTAGGG DNA重复顺序，具有维持染色体稳定性的功能。在鼠上皮癌的研究中发现端粒的缩短或丢失可引起染色体末端的融合，促进染色体异常的断裂及再融合。我们通过对喉鳞癌细胞系染色体端粒的表达和细胞分裂形态的检测和分析，研究端粒缺失和细胞分裂后期染色体桥现象是否存在于喉鳞癌，探讨二者之间潜在的关系。     

喉鳞状细胞癌患者预后的多因素分析

目的：探讨影响喉鳞状细胞癌患者预后的主要因素。方法：采用免疫组织化学SP法检测79例喉鳞状细胞癌患者肿瘤组织和10例癌旁正常组织中细胞s期激酶相关蛋白（Skp2）、p27、上皮细胞钙黏素（E-cad）、r连环素（α-cat）的表达,并对可能影响喉鳞状细胞癌患者预后的12项临床病理因素进行单因素和多因素分析。结果：①Skp2在喉鳞状细胞癌和癌旁正常组织中的表达率分别为53,16％和0,p27分别为30．38％和90．00％,E-cad分别为34．18％和100,00％,α-cat分别为40．51％和100,00％,其差异均有统计学意义（P〈0．05或P〈0．01）。②本组患者总的5年生存率为58．75％,Skp2蛋白低表达组的5年生存率（72．18％）显著高于高表达组（44．17％）（P〈0.01）;p27蛋白高表达组的5年生存率（72．98％）显著高于低表达组（51．13％）（P〈O．01）;E-cad及α-cat阳性表达组的5年生存率（分别为63．80％和81．74％）显著高于阴性表达组（分别为50.68％和41．09％）（P〈0．05和P〈0．01）。③单因素分析显示：病理分级,颈淋巴结转移,临床分期,T分期,复发,Skp2、p27、E-cad及α-cat表达对患者预后的影响均有统计学意义（P〈0．05或P〈0．01）;多因素分析显示：复发、Skp2及α-cat表达为影响患者预后的独立因素（P〈0．05或P〈O．01）。④Skp2和p27蛋白表达之间存在着负相关关系（P〈0.01）;p27和α-cat蛋白表达之间、E-cad和α-cat蛋白表达之间存在正相关关系（均P〈0．01）。结论：复发、Skp2及α-cat表达为影响喉鳞状细胞癌患者预后的重要因素。     

抑癌基因p15、Rb在喉鳞状细胞癌中表达的研究

目的 :研究抑癌基因p15、Rb蛋白表达对喉鳞状细胞癌诊断、治疗及预后判断的意义。方法 :用免疫组化SABC法检测喉癌组 45例石蜡标本与对照组 15例喉部正常或增生的黏膜上皮标本的 p15、Rb蛋白表达情况。结果 :喉鳞状细胞癌组p15蛋白阳性率 (48.9%)与对照组阳性率 (10 0 .0 %)比较 ,差异有极显著性意义 (P<0 .0 1) ;喉癌组中 0～Ⅱ期 p15蛋白阳性率 (6 6 .7%)与Ⅲ～Ⅳ期阳性率 (33.3%)比较 ,差异有显著性意义 (P <0 .0 5 ) ;喉癌组Rb蛋白阳性率 (88.9%)与对照组阳性率 (93.3%)比较 ,差异无显著性意义 (P >0 .0 5 ) ;2× 2列联表 χ2 检验 ,p15、Rb蛋白表达无相关性 (P >0 .0 5 ) ;对照组中 ,p15蛋白的表达以鳞状上皮组织中远离基膜的棘层细胞、颗粒层细胞明显 ,而Rb蛋白的表达则以基底层细胞及近侧棘层细胞明显。结论 :抑癌基因 p15的表达缺失对喉鳞状细胞癌的发生、发展有一定的作用 ,p15蛋白的检测对喉鳞状细胞癌的治疗及估计预后有指导意义 ;喉鳞状细胞癌组织中 p15、Rb的蛋白表达无相关性 ;正常及增生的喉部鳞状上皮的细胞层次间 ,p15、Rb蛋白表达不一致 ,p15蛋白表达对细胞增殖有抑制作用。     

喉癌细胞系中心体扩增与细胞异常分裂的检测

目的通过对喉鳞状细胞癌(简称喉癌)细胞系中心体表达和细胞分裂形态的研究,探讨中心体通过对细胞分裂过程的调控,在促进喉癌基因不断变异、发展机制过程中的作用。方法6个喉癌细胞系和4例喉癌旁正常组织上皮细胞培养。收获细胞经苏木素和伊红染色,观察分裂中期细胞核形态,计算核多极分裂像细胞百分比。应用抗γ-微管蛋白抗体免疫荧光染色检测细胞中心体,计算含异常中心体数目细胞的百分比。二组数据行直线相关分析。喉癌组和正常对照组两组数据平均值行t检验。结果喉癌细胞系多极核分裂像细胞平均占分裂中期细胞(11．53±4．54)％,含中心体扩增的细胞平均占总体细胞的(7．50±3．13)％。且二者呈显著正相关,r=0．814,P<0．01。而正常对照组细胞仅偶尔出现异常分裂中期形态及异常的中心体数目,其平均值分别为(0．83±0．99)％和(1．26±1．59)％。喉癌组和对照组两组数据平均值行t检验,喉癌组显著高于对照组,t值分别为3．522和3．877,P<0．01。结论喉癌细胞系表现为高度的中心体的扩增及细胞多极分裂,这在促进喉癌基因组不稳定性发展过程中起重要作用。