增殖细胞核抗原在鼻咽癌中表达的定量研究

为了增加鼻咽癌的诊断和预后判定指标，应用抗增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｎｅｃｌｅａｒａｎｔｉｇｅｎ，ＰＣＮＡ）单克隆抗体，采用免疫组化染色ＬＡＳ－ＳＰ法及图象分析技术，对８２例鼻咽鳞状细胞癌和２５例鼻咽粘膜炎症组织标本进行了定量研究，并对鼻咽癌患者５年生存率与ＰＣＮＡ表达情况进行了相关性分析。结果：①根据ＰＣＮＡ阳性细胞计算的鼻咽癌细胞增殖指数与鼻咽癌的病理分级呈明显的正相关，与患者５年生存率呈明显负相关。②图像处理检测的ＰＣＮＡ表达量与鼻咽癌的病理分级也呈明显的正相关，与５年生存率呈负相关，但泡状核细胞癌虽属低分化鳞癌却不符合上述规律。结论：ＰＣＮＡ能很好地反映鼻咽癌的增殖活性，在临床病理上具有应用前景，可作为对鼻咽癌预后判定及指导临床治疗的指标     

鼻咽癌细胞中蛋白酶ICH—1和增殖细胞核抗原表达的研究

目的：探讨蛋白酶ＩＣＨ－１与鼻咽癌发生的关系。方法：应用免疫组化ＳＰ法研究４６例鼻咽癌组织中ＩＣＨ－１和增殖细胞核抗原（ＰＣＮＡ）的表达。结果：４６例鼻咽癌中１６例ＩＣＨ－１Ｌ阳性，２２例ＩＣＨ－１Ｓ阳性，阳性率分别为３４８％和４７８％，ＩＣＨ－１Ｌ阳性细胞百分率为５４２％，ＩＣＨ－１Ｓ阳性细胞百分率为６８４％，较良性鼻咽上皮增加。４６例鼻咽癌细胞ＰＣＮＡ增殖指数为４９８±７２％，较良性鼻咽上皮增加，ＰＣＮＡ表达与癌细胞分化有关。结论：蛋白酶ＩＣＨ－１异常表达可能与鼻咽上皮癌变有关。ＰＣＮＡ可作为反映鼻咽癌细胞分化的一项指标。     

鼻咽癌病人端粒酶表达的研究

目的：研究端粒酶（ＴＬＭＡ）在鼻咽癌（ＮＰＣ）中的表达。方法：采用ＴＲＡＰ ＰＣＲ ＥＬＩＳＡ法探讨１８例ＮＰＣ，２例放疗后ＮＰＣ，４例癌旁组织及４例慢性鼻咽炎鼻咽部活检组织中ＴＬＭＡ表达。结果：１８例ＮＰＣ ＴＬＭＡ阳性率为８８．９％。４例癌旁组织阳性率为７５．０％，慢性鼻咽炎全部为阴性。１例复发性ＮＰＣ为阳性，１例疗后未复发为阴性。ＴＬＭＡ表达与ＮＰＣ分期、颈淋巴结转移似无明显关系。结论：ＴＬ     

鼻咽脱屑细胞涂片AgNOR计数的诊断意义

对４５例鼻咽癌（ＮＰＣ）患者鼻咽脱屑细胞涂片及活检组织切片的ＡｇＮＯＲ活性进行了对比观察，结果二者的ＡｇＮＯＲ活性表达趋势基本平行，且均明显高于鼻咽良性肿瘤、炎症及正常对照组，助记词肖可能应用于ＮＰＣ的诊断、动态观察及癌前病变随访的参考。     

唾液酸与急相蛋白对鼻咽癌的诊断价值

于１９９１年测定了鼻咽癌（ＮＰＣ）和喉癌（ＬＣ）患者血清唾液酸（ＳＡ）和５种急相蛋白（ＡＰＰｓ），其中包括前清蛋白（ＰＡ），ａ＿１－抗胰蛋白酶（ａ＿１－ＡＴ），ａ＿１－酸性糖蛋白（ａ１－ＡＧＰ），触珠蛋白（ＨＰ）和转铁蛋白（ＴＦ），并将上述测定值组合入判别函数式，用于ＮＰＣ和ＬＣ的计算机辅助诊断和随访。本文为验证１９９１年报道的判别函数式，对２３８例未知诊断的初诊患者，双盲法检测血清ＳＡ、５ＡＰＰｓ和鼻咽组织活检及临床检查，结果发现：鼻咽癌的判别函数诊断与临床检查及活检结果符合率均在８０％以上。     

鼻咽癌血管生成及血小板聚集功能与侵袭转移关系？…

目的：探讨鼻咽癌血管生成及血小板聚集功能与ＮＰＣ侵袭转移关系，为在分子水平干预肿瘤血管形成，预防ＮＰＣ复发和转移打下基础。方法：采用免疫组织化学Ｓ－Ｐ法检测了５６例ＮＰＣ，２０例无瘤鼻咽部石蜡标本组织中的微血管密度及血管骨皮细胞生长因子表达。随访３年，ＮＰＣ复发转移１７例，无复发或转移３９例。结果：复发转移组的血小板聚集率ＭＡＲ，ＭＶＤ及ＶＥＧＦ的表达较无复发转移的表达高，差异有统计学意义；ＭＶＤ     

P~(15)蛋白在鼻咽癌中的表达

本实验采用华西医科大学第一附属医院门诊１９９２年上半年获取的５５例鼻咽部低分化鳞癌（ＮＰＣ）的活检存档标本，用１５例正常人鼻咽部组织蜡块作对照。所有标本作免疫组化ＬＳＡＢ法染色，测定Ｐ蛋白的表达。并对所有ＮＰＣ患者进行５年随访。结果表明，Ｐ蛋白在鼻咽部正常组织表达阳性率为１００％，鼻咽部低分化鳞癌阳性率为７０．９％，二者差别有统计学意义（Ｘ２＝４．１３，Ｐ＝０．０４７２）。Ⅰ－Ⅱ期、Ⅲ期和Ⅳ期ＮＰＣＰ蛋白表达阳性率分别为８３．３％、８０．０％、６０．７％，差别有统计学意义（Ｋｗ＝８．３０５０，Ｐ＝０．０４７３）；Ｔ１－Ｔ２、Ｔ３和Ｔ４期ＮＰＣ的Ｐ蛋白表达阳性率分别为８０．８％、７２．２％、４５．５％，差别有统计学意义（Ｋｗ＝１５．３４，Ｐ＝０．０３９４）；无颈淋巴结转移与有颈淋巴结转移组Ｐ蛋白表达阳性率分别为７７．８％、７０．３％，差别无统计学意义（Ｋｗ＝６．２７９３，Ｐ＝０．０５５７）；Ｐ表达阴性组与阳性组的５年生存率分别为：５６．７％、６８．１％，二者差别无统计学意义（Ｐｒ＝０．４７７５）。通过本实验提示：在ＮＰＣ的发生发展过程中有Ｐ１５蛋白丢失的参与；Ｐ１５蛋白表达可作为ＮＰＣ生物学行为的一个参考指标     

鼻咽泡状核细胞癌和低分化鳞癌的临床生物学行为的对比研究

目的：探讨鼻咽泡状核细胞癌（ＶＮＣＣ）和低分化鳞癌（ＰＤＳＣＣ）的临床生物学行为的差异性。方法：用原位杂交和免疫组化染色（ＳＰ法）技术,检测ＶＮＣＣ和ＰＤＳＣＣ癌组织中ＣｅｒｂＢ２、表皮生长因子受体（ＥＧＦＲ）和增殖细胞核抗原（ＰＣＮＡ）表达,用原位末端标记（ＩＳＬＥ）方法检测癌细胞凋亡,并对其预后和临床特征进行对比分析。结果：①ＶＮＣＣ的ＩＳＥＬ和ＰＣＮＡ染色强度指数（ＳＩ）明显高于ＰＤＳＣＣ;②ＶＮＣＣ的ＣｅｒｂＢ２、ＥＧＦＲｍＲＮＡ和ＣｅｒｂＢ２蛋白表达与ＰＤＳＣＣ无明显差别;③ＶＮＣＣ的５年生存率比ＰＤＳＣＣ高。结论：与ＰＤＳＣＣ比较,ＶＮＣＣ是一种生长增殖活跃、分化程度更低,但有较好预后趋向的一种癌型。     

抑癌基因p16,p21及p53在鼻咽癌的表达

目的：观察抑癌基因ｐ１６,ｐ２１及ｐ５３在鼻咽癌（ＮＰＣ）的表达,探讨其与ＮＰＣ的发生发展及预后的关系。方法：用免疫组化ＳＰ法检测了１１６例ＮＰＣ组织和１５例无瘤鼻咽（ＮＰ）组织的ｐ１６,ｐ２１及ｐ５３基因的表达情况。     

微血管密度与鼻咽癌生物学行为的相关性

探讨鼻咽癌血管生成与癌生物学行为的关系。方法采用免疫组织化学ＳＰ法检测了６５例ＮＰＣ、１５例鼻咽良性肿瘤、１５例无瘤者鼻咽部石蜡标本组织中的微血管密度及血管内皮细胞生长因子表达。     

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.     

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。     

Effect of Han-uvulopalatopharyngoplasty on flow-mediated dilatation in patients with moderate or severe obstructive sleep apnea syndrome

Abstract

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.     

效应蛋白酶受体-1在鼻咽癌组织中的表达及其与细胞增殖和凋亡的关系

目的：探讨凝血蛋白酶因子Xa（FXa）的效应蛋白酶受体-1（EPR-1）在鼻咽癌（NPC）组织中的表达及其与细胞增殖、凋亡之间的关系。方法：用免疫组织化学SP法检测NPC组织、癌旁交界组织各42例及鼻咽部黏膜慢性炎症组织30例中EPR-1、增殖细胞核抗原Ki-67的表达,以Ki-67代表细胞增殖指数（PI）;用TdT酶介导的生物素化dUTP缺口末端标记技术（TUNEL法）检测凋亡指数（AI）并进行统计学分析。结果：EPR-1在NPC的组织、癌旁交界组织、鼻咽部黏膜慢性炎症组织中的阳性表达率分别为76．1％、90．5％、100．0％,3组间差异有统计学意义（均P〈0．01）,与AI呈正相关（r=0．551,P〈0．01）,与PI呈负相关（r=-0．338,P〈0．05）。结论：EPR-1促进细胞凋亡,抑制细胞增殖,为以Survivin为靶向的NPC治疗开创新的途径。     

DNA index,cellular proliferative activity and nucleolar organizer regions in cancers of the larynx

The DNA index, expression of cell-cycle-related proteins — proliferating cell nuclear antigen (PCNA, cyclin) and Ki-67 — and the content of silver-binding nucleolar organizer regions (AgNORs) were evaluated in 30 unselected consecutive primary squamous cell carcinomas of the larynx. Results were compared and subsequently related to histological grading, lymph node status, pT category, and pathological stage. DNA content was non-diploid in 9 cases (30%). Mean AgNOR counts per tumor ranged from 2.52 to 8.76. PCNA and Ki-67 expressions were similar in 10 cases (33%). In the remaining cases, PCNA-positive cells usually outnumbered Ki-67-positive cells. No significant correlation was found among DNA index, PCNA and Ki-67 expressions, and AgNOR counts. Although there was a positive trend when Ki-67 was compared with histological grading, findings were not statistically significant. In contrast, a significant correlation was found between DNA index and lymph node status (P = 0.035), with a higher incidence of neck node metastases in non-diploid tumors. These data suggest that tumor ploidy can be correlated with lymph node spread in laryngeal squamous cell carcinoma and might be used as an additional prognostic factor when planning treatment.     

喉癌EGFR和PCNA表达及DNA含量的研究

研究喉鳞癌中表皮生长因子受体、增殖细胞核抗原的表达和ＤＮＡ含量,分析各指标间的相关性及与喉癌临床生物学行为和预后的关系。方法：用免疫组化ＳＰ法和图像分析仪检测正常喉粘膜、喉鳞癌的ＥＧＦＲ、ＰＣＮＡ和ＤＮＡ指数,结合临床资料进行分析。结果：喉鳞癌的ＥＧＦＲ的阳性表达率为５４．８％,与正常喉组织的差异有统计学意义,但ＥＧＦＲ的阳性表达与喉癌的病理分级和５年生丰率无显著相关,而ＰＣＮＡ阳性表达和ＤＩ则随     

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。     

Clinical application of proliferating cell nuclear antigen, oncoprotein p53 and tumor front grading analysis in patients operated on for laryngeal cancer

The authors assessed proliferating cell nuclear antigen (PCNA), p-53 oncoprotein and morphologic tumor front grading (TFG) in patients with advanced squamous cell carcinoma (SCC), of the larynx and a poor prognosis and tried to find a correlation with tumor stage, the Broders grading system, local and neck lymph node metastases, as well as nodal and local recurrences. In addition, utility of the parameters investigated was evaluated in developing a prognostic factor model, using uni- and multivariate Cox regression analysis. Included in this study were 54 patients (mean age 57 years ± 8.6). PCNA-positive staining was found in all but one patient with advanced disease, while p-53 stained positively in only 24 subjects (44.4%). The PCNA index ranged from 4.6 to 59.0% (mean, 23.4 ± 11.0) and the p-53 index varied from 4.0 to 42.0% (mean, 17.2 ± 8.6). The TFG score ranged from 9 to 23 points (mean, 15.1 ± 3.2). PCNA, p-53 and TFG were found to be the markers that provided significant additional information about the biological behavior of tumor cells. The high variability of the results (PCNA, p-53) and high percentage of negatively stained cells (p-53) reduced their application in clinical use. PCNA correlated with tumor grade, G (r = 0.38; P < 0.01), but negatively with nodal (N) disease(r = –0.37; P < 0.01). The mean values of PCNA and p-53 index were higher in the subgroup with local recurrences. Our present attempt to develop a useful prognostic factor model failed. Received: 26 September 1998 / Accepted: 1 March 1999     

Cyclin-dependent kinase inhibitor p27 is related to cell proliferation and prognosis in laryngeal squamous cell carcinomas.

An immunohistochemical study of both p27 and proliferating cell nuclear antigen (PCNA) was performed on 102 cases of laryngeal squamous cell carcinomas (LSCCs), and large variations in p27 expression were found among the tumours. Reduced expression of p27 was revealed in 54 (52.9 per cent) cases and correlated with tumour size, lymph node metastasis, and clinical stage, but did not correlate with age, sex, tumour site, or tumour grade. A significant positive correlation was found between the percentage of loss of p27 expression and the PCNA index (r = 0.844, p < 0.0001). Reduced expression of p27 was significantly correlated with both reducing disease-free and overall survival by univariate analysis. By multivariate analysis, reduced expression of p27, tumour grade, tumour size, lymph node metastasis as well as clinical stage were independent prognostic factors for overall survival of LSCCs. These findings indicate that reduced expression of p27 may be correlated with the malignant biological behaviour of LSCCs.     

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.