PCNA和Ki-67在脑膜瘤组织中的表达及其意义

目的：探讨增殖细胞抗原（PCNA）和Ki-67核抗原在脑膜瘤中的表达及其与肿瘤良、恶性及复发的关系。方法:采用LSAB法检测80例脑膜瘤组织中PCNA和Ki-67的表达。结果：恶性脑膜瘤PCNA标记指数（PCNALI）和Ki-67标记指数（Ki-67LI)明显高于良性脑膜瘤（P＜0．01）和非典型性脑膜瘤（P＜0．05），复发脑膜瘤PCNA LI显著高于未复发脑膜瘤（P＜0．01），复发脑膜瘤Ki-67LI也显著高于未复发脑膜瘤（P＜0．01），Ki-67表达与PCNA表达呈正相关。结论：脑膜瘤细胞标记指数可作为判断脑膜瘤良；恶性的客观指标之一，标记指数对预测脑膜瘤的复发有一定意义。     

Comparison of PCNA/cyclin immunohistochemistry with flow cytometric S-phase fraction in breast cancer

Kinetic index determined by enumeration of neoplastic cells positive for proliferative cell nuclear antigen (PCNA) in 70 breast carcinomas (avidin-biotin immunoperoxidase technique) was compared to synthesis-phase fraction (S-phase, or SPF) values obtained by flow cytometry (FCM) using a multiparametric, 2 color method (dual-label propidium iodide/cytokeratin-FITC). The percent PCNA positive tumor cells (12.5% mean, range 1–28%) was significantly greater in aneuploid tumors (14.2% mean, N=35) compared to diploid range tumors (10.7% mean, N=35) (p<0.05), and was correlated with SPF derived from ungated DNA histograms (12.5% mean ± 5.5%, r=0.45, p<0.001). Marginally stronger statistical correlations were observed between the PCNA index and SPF values calculated from cytokeratin-gated (15.8% mean, r=0.53, p<0.001) DNA histograms or from SPF values obtained following linear baseline debris subtraction (mean=8.1%, r=0.48, p<0.001). Significant associations were identified between PCNA index and prognostically important clinicopathologic parameters including nuclear grade (p=0.014), presence of necrosis (p=0.005), and angiolymphatic invasion (p=0.003). We conclude: 1) PCNA index is comparable to FCM SPF and correlates with factors of known prognostic importance in carcinoma of the breast; 2) baseline debris and contaminating events derived from non-epithelial cells both represent significant artifacts in proliferative fraction estimates derived from FCM DNA histograms; and 3) multiparametric analysis may represent one means of improving the specificity and clinical value of FCM SPF determinations.     

p53、p16蛋白及增殖细胞核抗原与胃癌生物学行为的关系

目的　探讨p5 3、p16蛋白及增殖细胞核抗原 (PCNA)异常表达与胃癌生物学行为的关系。方法　应用免疫组化ABC法 ,对 95例胃癌进行p5 3、p16蛋白表达产物和PCNA进行检测。结果　胃癌组织中p5 3、p16、PCNA阳性率分别为 49 5 % ( 4 7/ 95 )、2 0 0 % ( 19/95 )、78 9% ( 75 / 95 )。p5 3蛋白、PCNA在进展期胃癌 ( 5 3 5 %、82 6% )淋巴结阳性胃癌 ( 5 9 3 %、86 4% )表达率均高于早期胃癌( 11 1%、44 4% )和淋巴结阴性胃癌 ( 3 3 3 %、66 7% ) (P <0 0 5 )。p5 3蛋白、PCNA在累及浆膜胃癌的表达率高于局限粘膜及粘膜下层胃癌 (P <0 0 5 ,P <0 0 1)。PCNA异常表达与胃癌组织学分型有关 (P <0 0 5 )。p16蛋白表达与胃癌大多数生物学行为无明显关系 ,但其在淋巴结阳性胃癌中的表达率 ( 11 9% )低于淋巴结阴性胃癌中的表达率 ( 3 3 3 % ) (P <0 0 5 )。p5 3阳性组织大多数伴PCNA阳性表达 (P <0 0 1)。结论　p5 3蛋白、PCNA异常表达在胃癌浸润转移过程及增殖中均起重要作用。p16蛋白表达缺失可能是胃癌淋巴结转移的重要促发因素。     

<Superscript>99m</Superscript>Tc-Tetrofosmin brain SPECT in the assessment of meningiomas—correlation with histological grade and proliferation index

Meningiomas account for about 30% of all intracranial tumors. Evaluation of their proliferation rate is useful for assessing their biological behavior. We evaluated prospectively whether (99m)Tc-Tetrofosmin ((99m)Tc-TF) uptake in meningiomas correlates with cellular proliferative activity and with tumor grade. We prospectively studied 18 meningioma cases. Brain single-photon emission computed tomography (SPECT) by (99m)Tc-TF was performed within a week prior to surgical excision. In the excised tumor specimens we assessed Ki-67 antigen expression. 14 of 18 patients had benign meningiomas, while the remaining four had anaplastic meningiomas. A significant correlation was found between both (99m)Tc-TF uptake and tumor grade (r = 0.722, P = 0.001) and between (99m)Tc-TF uptake and Ki-67 expression (r = 0.930, P < 0.001). There was a significant correlation between the intensity of tracer uptake and tumor recurrence at 1 year postoperative (r = 0.574, P = 0.02). This pilot study implies that (99m)Tc-TF brain SPECT could prove useful in differentiating benign from anaplastic meningiomas and is a potential indicator of their proliferative activity.     

Prognostic significance of Ki-67 (MIB1), PCNA and p53 in cancer of the oropharynx and oral cavity

Up to now results concerning the prognostic value of tumor proliferation markers in squamous cell head and neck carcinoma have been equivocal. Beside biological reasons, different treatment modalities are hypothetically responsible for contradictory findings. The aim of this study was to investigate the relationship between proliferative capacity, represented by the immunohistochemical labeling index of proliferation markers Ki-67, PCNA and p53 status, and treatment failure in a matched-pair study design of recurrent and non-recurrent carcinoma initially treated with primary surgery combined with curative post-operative radiation. From a group of 239 patients with T1–T3 carcinoma of the oropharynx or oral cavity, 28 patients with recurrent disease were selected and matched with 28 patients with non-recurrent disease regarding stage and location of tumor as well as age and therapy. All patients received primary surgery combined with post-operative radiation. Immunohistochemistry determined the p53 status and the PCNA and MIB1 (Ki-67) labeling index. The Ki-67 labeling index was significantly (p=0.032) higher in tumors from patients suffering from treatment failure (mean=59.1%) than in non-failures (mean=50.5%). Carcinoma with a Ki-67 (MIB1) labeling index above the median (53.7%) of the general study population showed a mean time to relapse of 45 months (n=25), whereas mean time-to-relapse was 61.7 months for those cases (n=31) below the median of the general study population (p=0.029). The PCNA labeling index did not correlate significantly with tumor recurrence (mean=50.2% for treatment failures, 45% for non-failures, p=0.31), nor with time-to-relapse (p=0.26). Forty-six percent of tumors showed p53 over-expression. However, there was no significant correlation between p53 over-expression and tumor recurrence or time-to-relapse. We present the largest series of oropharyngeal and oral cavity carcinoma investigated by immunohistochemistry in a controlled study. We conclude that a high Ki-67 labeling index is an indicator for treatment failure in these patients. Like other investigations for different head and neck subsites, we found no relationship between p53 or PCNA status and tumor prognosis. Our data, obtained from a group of patients treated with a combination of surgery and post-operative irradiation, show that for squamous cell carcinoma of the oropharynx and oral cavity the detection of Ki-67 is an unfavorable prognostic factor.     

喉癌p16,c—myc及PCNA表达的临床病理研究

探讨ｐ１６、ｃ－ｍｙｃ及ＰＣＮＡ在喉癌发病中的作用。方法应用ＳＡＢＣ免疫组化技术，检测４０例喉鳞癌手术标本中Ｐ１６、ｃ－ｍｙｃ及ＰＣＮＡ的表达，对三者表达与喉癌发生部位，临床分期，组织学分级和临床复发之关系进行探讨。     

Antigen expression on recurrent meningioma cells

Introduction

Meningiomas are intracranial brain tumours that frequently recur. Recurrence rates up to 20% in 20 years for benign meningiomas, up to 80% for atypical meningiomas and up to 100% for malignant meningiomas, have been reported. The most important prognostic factors for meningioma recurrence are meningioma grade, meningioma invasiveness and radicality of neurosurgical resection. The aim of our study was to evaluate the differences in antigenic expression on the surface of meningioma cells between recurrent and non-recurrent meningiomas.

Methods

19 recurrent meningiomas and 35 non-recurrent meningiomas were compared regarding the expression of MIB-1 antigen, progesterone receptors, cathepsin B and cathepsin L, using immunohistochemistry.

Results

MIB-1 antigen expression was higher in the recurrent meningioma group (p=0.001). No difference in progesterone receptor status between recurrent and non-recurrent meningiomas was confirmed. Immunohistochemical intensity scores for cathepsin B (p= 0.007) and cathepsin L (p<0.001) were both higher in the recurrent than in the non-recurrent meningioma group.

Conslusions

MIB-1 antigen expression is higher in recurrent compared to non-recurrent meningiomas. There is no difference in expression of progesterone receptors between recurrent and non-recurrent meningiomas. Cathepsins B and L are expressed more in recurrent meningiomas.     

脑膜瘤的临床病理及PCNA标记的研究

目的：为能准确预见脑膜瘤的生物学行为，并对术后辅助治疗与否提供参考依据。方法：对35例脑膜瘤组织行增殖细胞核抗原（PCNA）免疫组化染色，并结合图像定量分析及常规病理分型进行研究。结果：PCNA标记指数随肿瘤恶性程度而增高。结论：PCNA免疫组化检测方法能较好地反映脑膜瘤的增殖活力，可作为术后辅助治疗及定期复查与否的可靠指标。     

脑膜瘤DNA流式细胞术分析的临床病理学意义

目的探讨脑膜瘤细胞DNA倍体和增殖活性与脑膜瘤组织病理分型及生物学特性的关系.方法采用流式细胞仪检测42例脑膜瘤细胞DNA倍体和S期比例(SPF)、增殖指数(PI),结合肿瘤病理学类型进行相关性分析.结果在不典型、恶性脑膜瘤细胞中,非整倍体比例、SPF、PI显著性增高(P＜0.01);在组织亚型之间,各参数无显著性差异(P＞0.05):SPF、PI在非整倍体细胞系和复发脑膜瘤细胞中显著性增高(P＜0.01).结论流式细胞术分析是研究脑膜瘤细胞动力学和生物学特性的重要方法.DNA非整倍体可作为判定肿瘤恶性程度的指标.SPF、PI作为细胞增殖的指标,对脑膜瘤恶性程度和预后的评估具有重要意义.     

Cellular manifestations of human papillomavirus infection in laryngeal tissues

BACKGROUND AND OBJECTIVES: Although epidemiologic studies have suggested human papillomavirus (HPV) to be an etiological agent in laryngeal carcinogenesis, little is known on the cellular manifestations of HPV infection in these tumors. In this study, we investigated the frequency of HPV infection in various neoplastic and non-neoplastic laryngeal tissue and its association with expression of the proliferating cell nuclear antigen (PCNA) and the tumor suppressor protein p53. METHODS: Tissues were analyzed by polymerase chain reaction (PCR) for the presence of HPV and by immunocytochemistry for the expression of p53 and PCNA. RESULTS: None of the six normal laryngeal tissues showed the presence of HPV. Thirteen out of the 16 papillomas were positive for HPV, while 15 out of the 44 invasive cancers were HPV positive. PCNA expression increased as the lesion progressed through increasing histological abnormality (r = 0.64400, P = 0.00000). The correlation between the type of laryngeal neoplasm and p53 accumulation was significant (r = 0.54839, P = 0.00000). Significant correlation was also evident between presence of HPV and p53 accumulation (r = 0.34259, P = 0.00424) and PCNA expression (r = 0.036024, P = 0.00266) indicating that HPV positive tumors showed significant p53 accumulation and increased proliferation.There was also correlation between p53 and PCNA expression (r = 0.67475, P = 0.00000) indicating that in all tumors with p53 accumulation, there was a corresponding increase in PCNA expression. CONCLUSIONS: The results suggests that changes in p53 and PCNA expression may be associated with HPV infection, and could play a role in laryngeal carcinogenesis.     

56例瘤周脑水肿与脑膜瘤增殖及术后复发的临床意义

目的:探讨瘤周脑水肿(Peritumor brain edema,PTBE)程度与脑膜瘤细胞增殖及术后复发之间的关系.方法:分析56例Simpson Ⅰ～Ⅱ级切除的脑膜瘤患者,按术前瘤周脑水肿程度分为无、轻和重度水肿组,术后测定各组肿瘤增殖细胞核抗原(Proliferating cell nuclear antigen,PCNA)表达水平,分析瘤周水肿程度、PCNA标记指数(PCNALI)及术后复发之间的关系.结果:56例患者中5例复发,复发率为8.93%,其中轻度水肿1例,重度水肿4例.36例可在术前CT或MRl观察到瘤周脑水肿,3组的PCNA LI分别为(0.99±0.16)%,(2.87±0.36)%,(3.89±0.35)%,统计分析表明水肿程度与PCNA LI及复发率之间有较好的相关性.结论:瘤周脑水肿程度与脑膜瘤的增殖和术后复发密切相关,是预测肿瘤复发的一个良好指标.     

胃粘膜异型增生的PCNA、P53和C-erbB-2表达及其诊断价值

 应用免疫组化SP方法, 对65例异型增生胃粘膜PCNA(PC10)、CerbB-2(PAb1)和P53蛋白进行了测定。胃粘膜异型增生Ⅰ级PCNA平均指数22.34%, Ⅱ级32.58%, Ⅲ级46.08%, 各组间比较差异有显著性(P＜0.01), PCNA平均指数与异型增生病理分级间有很好地相关性(r＝0.966, P＜0.0005); Ⅰ、Ⅱ级异型增生无P(53)和C－erbB－2蛋白表达, Ⅲ级中P(53)蛋白阳性8例(32%), C-erbB-2蛋白阳性7例(28%)。 本文还就PCNA指数和P(53)、C－erbB－2蛋白表达的意义进行了讨论。     

p53功能在肝癌中表达的意义

为探讨Ｐ５３功能及某些生物学行为肝癌中表达的意义。方法：收集１９９７年１月至１９９８年１２月５２例原发性肝癌的临床资料，并对这５２例手术切除的肝癌标本，分别用Ｗｅｓｔｅｒｎ ｂｌｏｔ结合ＤＮＡ损伤诱导的方法检测野生型Ｐ５３的功能，免疫组化检测Ｐ５３蛋白的表达，ＰＣＲ／ＳＳＣＰ方法检测Ｐ５３基因在第５－８外显子的丢失情况及免疫组化检测肿瘤增殖细胞核抗原（ＰＣＮＡ）指数。结果：５２例标本中，３１例（５     

Correlation among [h-3] thymidine, flow-cytometry and proliferating cell nuclear antigen indexes in colorectal tumors

In colorectal cancer and other tumors, proliferating cell nuclear antigen (PCNA) has been found to be a useful marker in immunohistochemical studies of cell proliferation, The presence of a correlation among PCNA labeling index (PCNA LI) and values of cell proliferation expressed by [H-3]thymidine labeling index (TLI) and flow cytometry (FC), the most common techniques used in the evaluation of proliferative activity in colorectal cancer were studied. In 50 operable colorectal cancer patients, TLI, PCNA LI and determination of S-phase fraction by FC were carried out in order to evaluate the correlation among these three indices. A good correlation was obtained between PCNA LI and both TLI (r=0.667; P=0.0001) and percent of cells in S-phase as determined by FC (r=0.819; P=0.0001). It is concluded that PCNA immunohistochemistry can be a reliable marker of the proliferative activity in colorectal rumours. Furthermore, because of its technical simplicity and lower cost it can be more advantageous than TLI or FC.     

肝细胞癌p53蛋白、增殖细胞核抗原与临床关系的研究

目的　探讨在肝细胞癌中突变型 p5 3蛋白与增殖细胞核抗原 (PCNA)的相互关系及其意义。 方法　应用免疫组化ABC法检测肝细胞癌和肝硬化中 p5 3蛋白及增殖细胞核抗原。 结果　 37例肝细胞癌 (HCC)中 p5 3阳性 19例 ,33例肝硬化标本中p5 3阳性 2例 ,两者有显著差异 (P <0 .0 1) ;HCC中PCNA阳性细胞均数显著高于肝硬化组 (P <0 .0 1) ;p5 3阳性者PCNA阳性细胞数高于p5 3阴性者 (P <0 .0 5 )。p5 3与PCNA两者表达存在显著正相关关系 (r=0 .5 936 2 ,P <0 .0 5 ) ,p5 3表达与年龄、性别、组织分化无关 ,PCNA表达分别与组织分化及血AFP成负相关及正相关。结论　p5 3基因突变在由肝硬化转变为癌过程中是频发事件 ,其表达异常与HCC发生密切相关。PCNA与 p5 3的正相关提示p5 3突变型主要存在于异常增生细胞中 ,且PCNA可反映癌细胞分化及增殖程度 ,可为肝硬变与肝癌关系的探讨及临床诊断、治疗、预后提供参考资料。     

AR、PCNA表达与脑膜瘤临床病理因素的相关性研究

目的探讨雄激素受体(AR)在脑膜瘤组织中的表达及其与肿瘤增殖潜力的关系.方法采用免疫组化SABC法,检测AR、增殖细胞核抗原(PCNA)在39例脑膜瘤组织中的表达.结果51.3%(20/39)的脑膜瘤组织中AR呈不同程度的表达.良性、非典型性、恶性脑膜瘤中AR表达率分别为31.6%(6/19)、58.3%(7/12)、87.5%(7/8).恶性脑膜瘤中AR阳性细胞数显著高于非典型性和良性脑膜瘤(P＜0.05).恶性脑膜瘤平均PCNA标记指数(PCNA U)明显高于非典型性(P＜0.05)和良性脑膜瘤(P＜0.05).AR阳性脑膜瘤的PCNA U高于AR阴性脑膜瘤(P＜0.05),AR表达与PCNA的表达呈正相关.结论脑膜瘤AR表达与其病理级别有关,AR参与了肿瘤的生长和血管生成;检测脑膜瘤中AR表达可间接反映肿瘤的增殖潜力.     

消化道平滑肌肿瘤增值细胞核抗原表达及其诊断价值

应用增殖细胞核抗原（ＰＣＮＡ）免疫组织化学方法，研究了其在消化道平滑肌肿瘤中的表达。结果良性肿瘤的ＰＣＮＡ平均指数为６．７％，交界性肿瘤为１２．１２％，恶性肿瘤为３２．１９％。良性肿瘤与交界性肿瘤比较差异有显著性（Ｐ＜０．０５），交界性肿瘤与恶性肿瘤比较差异有显著性（Ｐ＜０．０１）。核分裂相与ＰＣＮＡ表达是相关性（ｒ＝０．７８５，Ｐ＜０．０００５），肿瘤大小与ＰＣＮＡ表达是相关性（ｒ＝０．４９６，Ｐ＜０．００２５）。结果提示ＰＣＮＡ染色有助于消化道平滑肌瘤的正确诊断。     

Expression of p53, MDM2 protein and Ki-67 antigen in recurrent meningiomas

Association of p53 gene abnormalities with tumor progression and prognosis of many neoplasms has been demonstrated, but little is known about the clinical significance of p53 abnormalities in meningiomas. The significance of p53 protein expression in recurrent meningiomas and its relationships with MDM2 protein and proliferation activity were investigated by analyzing 39 meningiomas immunohistochemically. p53 protein was expressed in 11 (35%) of 31 non-recurrent and 7 (88%) of 8 recurrent meningiomas. A high frequency of p53 expression was observed in recurrent meningiomas, which tended to have a high p53 positive index (p53 PI), indicating that p53 immunoreactivity may be a marker for predicting tumor recurrence. Four recurrent meningiomas with high p53 PIs were analyzed by the polymerase chain reaction-single strand conformation polymorphism method to detect p53 gene mutations, but none were found in exons 4–8 of this gene. Fifteen (71%) of 21 MDM2-positive and 3 (17%) of 18 MDM2-negative tumors expressed p53 protein, showing that MDM2 expression was more common in meningiomas with p53 expression. p53 immunoreactivity in the absence of mutation may indicate stabilization of the wild type through interaction with the MDM2 protein. The Ki-67/MIB-1 proliferation index (MIB-1 PI) correlated well with recurrence. The p53-positive tumors had a significantly higher mean MIB-1 PI than p53-negative tumors, suggesting that wild-type p53 inactivation by the MDM2 protein may be involved in controlling the proliferative activity in meningiomas. In conclusion, immunohistochemical examination for p53 protein as well as proliferative activity may help predict the malignant potential of tumor recurrence.