Ki-67、p53和VEGF在鼻咽癌组织中的表达及临床意义

目的探讨Ki-67、p53和VEGF在鼻咽癌组织中的表达及其临床意义。方法选择2015年1月至2020年7月在我院初诊的鼻咽癌患者90例为观察组,选择同期50例在我院就诊的鼻咽黏膜慢性炎症患者为对照组。通过免疫组化检测两组鼻咽组织中Ki-67、p53和VEGF的表达,并探讨三个免疫组化指标与临床病理特征之间的关系。结果(1)鼻咽癌组织中Ki-67、p53、VEGF阳性表达均明显高于鼻咽部炎症组(P<0.05)。(2)鼻咽癌组织中Ki-67、p53、VEGF阳性表达与患者的性别、年龄等病理因素没有相关性(P>0.05),与病理分型、颈部淋巴结转移以及临床分期具有密切相关性(P<0.05)。(3)Ki-67、p53、VEGF三者在鼻咽癌组织中的表达相互之间均呈正相关(P<0.05)。结论Ki-67、p53和VEGF与鼻咽癌的发生和发展有密切相关性,三者的检测对鼻咽癌的诊断及治疗具有重要的参考价值。     

COX-2蛋白在鼻咽癌中的表达及其临床意义

目的 探讨COX-2(cyclooxygenase-2)蛋白在鼻咽癌组织中的表达及其临床意义。方法 分别应用免疫组化方法（IHC）和蛋白印迹方法（Western Blot）检测47例鼻咽癌组织（其中用IHC33例,Western Blot14例）及24例鼻咽部炎症组织中COX-2蛋白的表达。结果 COX-2蛋白在鼻咽癌组织的阳性表达率为81.8%（27/33）,在鼻咽炎组织的阳性表达率为25%（3/12）,两者表达差异有统计学意义（P=0.001）。Western Blot结果显示,在两种组织中COX-2蛋白表达的相对值分别为1.258±0.034和0.487±0.076,在鼻咽癌组表达显著增高（P=0.000）。结论 COX-2蛋白的高度表达在鼻咽癌的发生、发展中起重要作用,选择性COX-2抑制剂有望成为鼻咽癌化疗的重要药物。     

鼻咽癌组织中bcl-2及P53蛋白表达的研究

目的 探讨bcl-2和P^53蛋白在鼻咽癌发生发展中的作用。方法 采用抗bcl-2和P^53蛋白的单克隆抗体，对25例鼻咽癌（Nasopharyngeal carcinoma,NPC)标本和16例正常鼻咽上皮（Nasopharyngeal epithelia,NE)标本进行免疫组化检测。结果 bcl-2和P^53蛋白的阳性表达率在鼻咽癌组织中分别为84．0％（21／25）和76．0％（19／25），与正常鼻咽上皮组相比差异有极显著性意义（P＜0．005）；鼻咽癌中有16例同时表达bcl-2和P^53蛋白。此外，bcl-2蛋白多见于分化差的鼻咽癌，而P^53蛋白则在相对分化较好的鼻咽癌中较多。结论 bcl-2原癌基因和P53抑癌基因在鼻咽癌的发病中可能有不同的意义，二种基因的协同作用可能与鼻咽癌持续生长有关。     

环氧化酶-2蛋白在鼻咽癌组织中的表达

目的 探讨环氧化酶-2（COX-2）蛋白在鼻咽癌组织中的表达及其临床意义。方法 应用免疫组织化学方法检测45例鼻咽癌组织及20例鼻咽黏膜不典型增生组织中COX-2的表达。结果 鼻咽癌组织中COX-2蛋白阳性表达率为71．1%（32／45），鼻咽黏膜不典型增生中COX-2蛋白阳性表达率为10．0%（2／20），两者比较差异具有统计学意义（P〈0．001）。结论 COX-2蛋白在鼻咽癌组织中表达增高，表明COX-2可能在鼻咽癌的发生发展中起重要的作用。     

增殖细胞核抗原及Bcl-2蛋白在鼻咽癌中的表达

目的:探讨鼻咽癌组织中增殖细胞核抗原(PCNA)、Bcl-2表达情况及与主要临床指标间的关系。方法:以免疫组化检测鼻咽活检组织中PCNA、Bcl-2蛋白表达,并比较与分析两者和鼻咽癌临床分期及颈淋巴结转移的关系。结果:鼻咽部慢性炎性组织中Bcl-2阳性率为9.5％,明显低于鼻咽癌组织中的阳性率(83.1％)(P<0.01)。PCNA、Bcl-2在鼻咽癌中的表达呈明显负相关(r_s=-0.41,P<0.01)。随着临床分期的增高,PCNA增殖指数(PI)分级有增高的趋势,鼻咽癌伴颈淋巴结转移组中PI之Ⅰ级所占比例,较无颈淋巴结转移组下降,而Ⅱ、Ⅲ、Ⅳ级所占比例增加,但无统计学意义。结论:PCNA PI可反映鼻咽癌的增殖状况,可能与预后相关,Bcl-2蛋白可作为鼻咽癌较好的肿瘤标记物,在鼻咽癌的发生上可能起重要作用。     

鼻咽癌中环氧化酶-2和潜伏膜蛋白-1的表达和相互关系的初步研究

目的：探讨鼻咽癌组织中的环氧化酶2（COX-2）、潜伏膜蛋白-1（LMP1）的表达情况,同时分析了两者之间的关系。方法：53例鼻咽癌活检标本,8例鼻咽部慢性炎症常规石蜡切片标本作为对照组,用SP免疫组织化学法检测COX-2、LMP1的表达,采用sPsS12．0统计软件对实验数据进行统计。结果：在鼻咽癌组织中,COX-2阳性表达率为71．70％（38／5a）;LMPI阳性表达率为66．04％（35／53）。COX2、LMP1的表达在颈部淋巴结转移组中均明显高于无颈部淋巴结转移组（P％O．05）,但在年龄、性别、病理类型、临床分期的分组中均差异无统计学意义（均P〉0．05）。在鼻咽癌组织中,LMP1和COX-2的表达存在正相关（7—0．797,P〈0．01）。结论：COX-2、LMP1在鼻咽癌组织中均有表达。COX2、LMP1在鼻咽癌中的表达和鼻咽癌颈淋巴结转移存在显著相关性,但和年龄、性别、病理类型、临床分期无相关性。COX-2和LMP1在鼻咽癌组织中的表达呈正相关。LMP1可能通过多途径上调COX-2的表达,从而促进鼻咽癌颈部淋巴结转移。     

增殖细胞核抗原和p53基因在鼻咽癌中的表达及相关性研究

目的:通过免疫组织化学方法检测鼻咽癌(NPC)患者增殖细胞核抗原(PCNA)、p53基因表达,分析其与主要临床指标间的关系。方法:免疫组织化学检测鼻咽活检组织中PCNA、p53蛋白表达,并比较与分析两者和NPC临床分期及颈淋巴结转移的关系。结果:鼻咽部慢性炎性组织中p53阳性率为9.5%,明显低于NPC组织中的阳性率(76.3%)(P<0.01)。NPC伴颈淋巴结转移组p53阳性率(90.9%)明显高于无颈淋巴结转移组(57.7%)(P<0.01),临床Ⅱ、Ⅲ和Ⅳ期p53阳性率(分别为93.3%、80.0%和100.0%)均明显高于临床Ⅰ期(40.0%)(均P<0.01),且表达强度有增加的趋势。随着临床分期的增高,PCNA增殖指数(PI)分级有增高的趋势,NPC伴颈淋巴结转移组中PCNAPI之Ⅰ级所占比例较无颈淋巴结转移组下降,而Ⅱ、Ⅲ、Ⅳ级所占比例增加,但无统计学意义,NPC组织中PCNA表达与p53表达显著相关(P<0.01)。结论:p53蛋白可作为NPC较好的肿瘤标记物,p53阳性的NPC患者较易发生颈淋巴结转移,随着NPC病程的发展,p53表达率及表达强度均增加,PCNAPI可反映NPC的增殖状况,可能与预后相关。     

鼻咽上皮细胞异型性改变与PCNA及MMP-9表达的相关性研究

目的 研究鼻咽上皮细胞癌变过程中不同阶段的增殖细胞核抗原（PCNA）及金属基质蛋白酶9（MMP-9）表达活性.方法 在鼻咽癌高发区,选择慢性鼻咽炎30例、鼻咽上皮细胞不典型增生或化生者42例及鼻咽癌34例作为研究对象,以免疫组化S-P方法检测PCNA及MMP-9表达水平.结果 PCNA在鼻咽炎、不典型增生或化生鼻咽上皮细胞、鼻咽原发灶癌组织表达活性分别为10.0%、73.8%、82.4%,而MMP-9在这些组织的表达水平分别为0.0%、38.1%、67.6%,活性表达差异均具有统计学意义（P＜0.001）.结论 在鼻咽上皮细胞癌变过程中,PCNA及MMP-9依病理分级严重程度而呈现表达增强趋势.     

端粒酶HTRT在鼻咽癌及癌前病变中的表达

目的观察端粒酶HTRT在鼻咽癌及癌前病变中的表达,探讨其在鼻咽上皮癌变中的可能作用.方法运用免疫组化(LSAB)法检测端粒酶HTRT在正常鼻咽黏膜、鼻咽黏膜异型增生和鼻咽癌组织中的表达.结果鼻咽正常黏膜全部为阴性,异型增生鼻咽组织阳性表达率较低,而鼻咽癌组织HTRT阳性表达率明显升高,但其表达与肿瘤分化程度、临床分型及淋巴结转移不相关.结论HTRT表达在鼻咽癌发生中起一定作用.     

鼻咽癌细胞中MDM2基因的扩增与表达及其与p53的表达、EB病毒潜伏感染、细胞增生的关系(英文)

目的：明确鼻咽癌（NPC）细胞中小鼠双微粒体基因（MDM2）的扩增与表达情况及其作用。方法：应用斑点杂交、半定量逆转录一多聚酶链反应技术、原位杂交、免疫组化分别对NPC、慢性鼻咽炎症粘膜CINE）进行MDM2基因扩增与表达的检测；运用免疫组化、PCR分别对NPC、CINE中p53表达、PCNA和Ki67指数、EB病毒DNA进行检测；同时分析MDMZ的过表达与p53表达、PCNA和Ki67指数、EB病毒潜伏感染、NPC各临床病理参数的关系。结果：3．1％的NPC有MDM2基因的扩增，30.8％有MDM2mRNA高表达，30.4％有MDM2蛋白的过表达；MDM2的过表达与p53表达（p＜0.05）、NPC颈淋巴结转移相关（p＜O．05），而与EBV潜伏感染，PCNA和Ki67指数、NPC的T分期、NPC病人的年龄、性别、EBVCA-IgA滴度无关。结论：MDM2基因在NPC组织中的主要活化方式是过表达而不是扩增；MDM2基因可能通过与p53相互作用而NPC的发生和转移过程中起着重要作用。     

Correlation between proliferating cell nuclear antigen and p53 protein expression and 5-year survival rate in nasopharyngeal carcinoma

PURPOSE: To assess the prognostic significance of p53 protein and proliferating cell nuclear antigen (PCNA) expression in nasopharyngeal carcinoma. MATERIALS AND METHODS: This study included 79 patients who had received treatment and regular follow-up for at least 5 years at a single institute. We used immunohistochemistry staining to assess p53 protein expression and PCNA labeling index (LI). Analyses were conducted on the association between each of the 2 biomarkers and pathological subtypes, TNM stage, the presence of locoregional recurrence, and 5-year survival rate. RESULTS: p53 protein nuclear staining was positive in 49 patients (62%). The mean PCNA LI was 55.6%, ranging from 3.35% to 92.9%. High PCNA LI (>55.6%) might contribute to higher 5-year survival rate, but it did not reach statistical significance (P = .09). Positive p53 protein staining and low PCNA LI were associated with the presence of locoregional recurrence. No statistical significance was found between p53 protein expression and PCNA LI and pathological subtypes and TNM stage. CONCLUSION: p53 protein and PCNA LI were not an ideal prognostic indicator in predicting 5-year survival rate in nasopharyngeal carcinoma. Future work will direct toward searching for other potential biomarkers with the hope to reinforce prediction of prognosis.     

Skp2与P27kip1在鼻咽癌组织中的表达及意义

目的：F-box蛋白家族中的一员Skp2参与细胞周期抑制蛋白P27kip1泛素化降解,研究发现Skp2在乳腺癌、胃癌、前列腺癌等多种恶性肿瘤中表达增加。本研究旨在探讨Skp2与P27kip1在鼻咽癌组织中的表达及与鼻咽癌多项临床病理特征的关系,并探讨两者的相关性。方法：鼻咽癌组39例,慢性鼻咽炎组24例。标本均经石蜡包埋,HE染色确诊。Skp2和P27kip1蛋白的检测采用免疫组化染色（PV-9000二步法）。结果：(1) Skp2在鼻咽癌组织中的阳性表达率为71.79%,明显高于其在慢性鼻咽炎组织中的阳性表达率(41.67%),差异有统计学意义（P＜0.05）;P27kip1在鼻咽癌组织中的阳性表达率为35.90%,明显低于其在慢性鼻咽炎组织中的阳性表达率(79.17%),差异有统计学意义（P＜0.01）;(2) Skp2、P27kip1的蛋白表达与鼻咽癌的临床分期、颅神经侵犯有关（P＜0.05）,与年龄、性别、分化程度、颈淋巴结转移无关（P＞0.05）;(3) Skp2、P27kip1在鼻咽癌组织中的表达呈负相关（rs=-0.373,P=0.019）。结论：鼻咽癌中Skp2蛋白表达与靶蛋白P27kip1蛋白降解有关,Skp2、P27kip1可能与鼻咽癌的发生发展有关,联合检测Skp2、P27kip1蛋白表达可作为判断鼻咽癌生物学行为的指标之一。     

The prognostic value of proliferating cell nuclear antigen (PCNA) and p53 protein expression in patients with advanced nasopharyngeal carcinoma

CONCLUSION: p53 protein and proliferating cell nuclear antigen (PCNA) were not ideal prognostic indicators in advanced nasopharyngeal carcinoma (NPC). Further investigation in searching for other potential biomarkers is needed to enhance the prediction of treatment outcome. OBJECTIVE: To assess the prognostic significance of p53 protein and PCNA expression in patients with advanced NPC. PATIENTS AND METHODS: This study included 46 patients with advanced NPC who had received treatment and regular follow-up for at least 5 years. We used immunohistochemistry (IHC) staining to assess p53 protein expression and PCNA labeling index, and correlate them with pathological subtypes, TNM stage, the presence of locoregional recurrence, and 5-year survival rate. RESULTS: p53 nuclear staining was positive in 32 patients (69.6%). All cases had positive PCNA nuclear staining with labeling index (LI) ranging from 6.5% to 92.9% (mean 53.4%). Only advanced T stage was found to be associated with high PCNA LI. Overexpression of p53 and PCNA LI had no impact on 5-year survival in this study group.     

Detection of Epstein‐Barr Virus–Derived Latent Membrane Protein‐1 Gene in Various Head and Neck Cancers: Is It Specific for Nasopharyngeal Carcinoma?

OBJECTIVE: The object of the study was to determine the incidence of the presence of Epstein-Barr virus-derived latent membrane protein-1 (LMP-1) gene in various head and neck cancers by polymerase chain reaction method. STUDY DESIGN: Prospective study. METHODS: During a 5-year period, polymerase chain reaction was used to investigate the presence of LMP-1 gene in various head and neck cancers from different locations and histopathological types, noncancerous nasopharyngeal biopsy samples, and tonsillectomy specimens from patients with chronic hypertrophic tonsillitis. RESULTS: Of 202 patients enrolled in the study, 53 were diagnosed by pathological study with oropharyngeal carcinoma, 45 with nasopharyngeal carcinoma, 26 with oral cavity carcinoma, 26 with laryngohypopharyngeal carcinoma, 31 with nasopharyngeal lymphoid hyperplasia, and 21 with tonsils with lymphoid hyperplasia. After the application of polymerase chain reaction, the LMP-1 gene was not detected in any sample from oral cavity carcinoma, laryngohypopharyngeal carcinoma, or nasopharyngeal lymphoid hyperplasia or from tonsillectomy specimens but was detected in only one case of tonsillar carcinoma. On the contrary, the LMP-1 gene was detected in 43 (95.6%) of 45 samples from patients with nasopharyngeal carcinoma. The statistical analysis shows a significant association (P <.001) between the presence of LMP-1 gene and tumor localization in the nasopharynx. CONCLUSIONS: The study shows that the presence of LMP-1 gene detected by polymerase chain reaction in the tumor cell is only significantly associated with tumor located in the nasopharynx, implying that Epstein-Barr virus plays a trifling role in the tumorigenesis of carcinomas arising from other head and neck locations. The polymerase chain reaction method that was used is a potential tool for screening nasopharyngeal carcinoma.     

喉癌中脉管生成相关因子与微血管密度和淋巴管密度的关系及临床意义

目的探讨喉癌组织中缺氧诱导因子-1α(hypoxia inducible factor 1 alpha,HIF-1α)、环氧化酶-2(cyclooxygenase 2,COX-2)的表达与微血管和淋巴管密度的关系。方法通过免疫组化SP法对64例声门上型喉癌标本中HIF-1α、COX-2与微血管密度(microvessel density,MVD)CD34标记及微淋巴管密度(lymph vessel density,LVD)D2-40标记进行了检测。结果喉癌中HIF-1α及COX-2蛋白阳性表达率分别为67.18%(43/64)、70.31%(45/64),MVD为36.79±8.48,LVD为9.68±6.35。喉癌HIF-1α、COX-2表达阳性者的MVD及LVD明显高于阴性者。喉癌中HIF-1α和COX-2之间存在相关性(r=0.492,P<0.05)。颈淋巴结转移组中HIF-1α、COX-2阳性表达率(χ2分别为6.615、5.534、P<0.05)及MVD和LVD(t分别为5.58、7.43,P<0.05)明显高于非转移组,差异有统计学意义。结论 HIF-1α、COX-2可能参与喉癌的血管及淋巴管生成,HIF-1α可能通过调节下游基因的表达,在喉癌血管及淋巴管生成中发挥重要作用,共同参与喉癌颈淋巴结转移过程。     

Salivary gland tumors in children and adolescents: a clinicopathologic and immunohistochemical study of fifty-three cases

OBJECTIVE: Salivary gland tumors in children and adolescents are rare. Most papers are case reports or short series of cases. The aim of this study was to analyze clinicopathological and immunohistochemical data from a large series of salivary gland tumors affecting youngsters from a single institution. METHODS: From 1953 to 1997, 53 patients 18 years old or less with epithelial salivary gland tumors from the Hospital do Cancer A.C. Camargo were studied. Clinical and treatment data were obtained from the medical records and histological features were reviewed. Paraffin-embedded tissues were immunohistochemically analyzed for p53, PCNA, Ki-67, bcl-2, c-erbB-2, and CEA. RESULTS: Twenty-seven tumors (51%) were benign and 26 (49%) malignant. Pleomorphic adenoma (PA) was the most common tumor type (49%), followed by mucoepidermoid carcinoma (MEC, 39.6%). The tumors were more common in female and 50.9% of the cases affected the parotid, followed by 26.4% of intraoral involvement. Immunohistochemical analysis did not show correlation with prognosis of the tumors. Twenty (74%) of the 27 patients with benign tumors were alive without evidence of disease after a mean of 16.5 years of follow up; 6 were lost of follow up and 1 died by causes not related to the disease. Nineteen (73%) of the 26 patients with malignant tumors did not show tumoral recurrence after a mean follow up of 14.3 years, and 3 (11.5%) patients died of the disease. CONCLUSIONS: In 53 cases of epithelial salivary gland tumors in youngsters, half were malignant, with favorable prognosis. On this series, immunohistochemical expression of p53, PCNA, Ki-67, c-erbB-2, bcl-2, and CEA, were not correlated with prognosis.     

上颌窦鳞癌两种癌基因及增殖细胞核抗原的表达及意义

目的 检测上颌窦鳞癌、上颌窦内翻性乳头状瘤及上颌窦炎性粘膜中ｒａｓ、ｐ５３及增殖细胞核抗原的表达情况，并分析其表达与上颌窦鳞癌临床病理特性和预后的关系。方法 应用免疫组织和化学方法检测４０例上颌窦鳞癌、２０例上颌窦内翻必 状瘤、１０例上颌窦炎性粘膜中ｒａｓ、ｐ５３、ＰＣＮＡ的表达情况。结果 ｒａｓ基因表达与上颌窦鳞癌分化程度有关，其表达多见于高分化鳞癌中；Ｐ５３基因表达只出现在上颌窦鳞癌中，在上颌     

喉鳞状细胞癌组织中骨桥蛋白和p53的表达及其临床意义

目的 研究人喉鳞状细胞癌（LSCC）及其癌旁相对正常组织中骨桥蛋白 (OPN)和p53表达水平,并探讨两者的相互关系及其临床病理学意义。方法 采用免疫组织化学SP法,对44例LSCC及癌旁组织手术切除标本常规制作石蜡包埋切片,检测OPN和p53的表达,结合喉癌患者的临床病理学特征进行分析。结果 ①44例喉癌组织中OPN和p53表达阳性率分别为75.0%（33例）和65.9%（29例）,癌旁相对正常组织中分别为13.6%（6例）和2.3%（1例）;②OPN的表达与颈部淋巴结转移、临床分期、病理组织学分级有关,与性别、年龄、原发部位无相关性;③OPN和p53的表达呈显著正相关（r＝0. 360,P＝0.016）。结论 OPN在喉癌组织中的表达高于癌旁相对正常组织,可能参与了喉癌的发生、发展和转移,有可能成为判断预后的重要生物学标记物。