Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in unicystic ameloblastoma

The expression of proliferating cell nuclear antigen (PCNA) and Ki-67 was studied in unicystic and solid ameloblastoma (follicular and plexiform types) using a biotin-streptavidin method on routinely processed paraffin sections. To determine percentage PCNA and Ki-67 labelling indices, positive tumour cells and total tumour cells were counted in areas of each unicystic ameloblastoma corresponding to cystic linings, intraluminal nodules and invading tumour islands, and in solid ameloblastomas. Positive cells in basal and suprabasal layers of cystic tumour lining were also counted with respect to the length of basement membrane determined by image analysis. In unicystic ameloblastoma the invading islands exhibited a significantly higher PCNA labelling index (29.2 ± 16.4%) than intraluminal nodules (13.6 ± 5.4%; P < 0.05). Cystic tumour lining had relatively few PCNA positive cells and a labelling index (5.5 ± 3.3%) significantly lower than invading islands (P < 0.001) or intraluminal nodules (P < 0.003). The labelling indices of solid ameloblastomas of follicular type (48.1 ± 12.9%) were significantly higher than those of cystic tumour lining (P < 0.0001), intraluminal nodules (P < 0.001) and invading islands (P < 0.04) in unicystic ameloblastoma. Similar relationships were found for Ki-67 expression except that comparisons involving invading islands and intraluminal nodules were not significant, a finding probably due to the smaller number of specimens available for quantitative analysis. These results indicate differences in proliferative potential between different areas of unicystic ameloblastoma and between unicystic and solid lesions. The fact that invading tumour islands within the fibrous tissue wall showed high labelling indices is in agreement with the clinical observation that their presence may be related to recurrence after conservative surgery. This provides a biological basis for indicating more radical surgical excision as the treatment of choice for this subgroup of lesions.     

Depressed adenoma of the colorectum: Analysis of proliferative activity using immunohistochemical staining for proliferating cell nuclear antigen (PCNA)

Recently, depressed adenomas (DA) of the colorectum have been frequently detected in Japan. The natural history and carcinogenesis of these DA remain unclear. The histological features and cell kinetics of 13 DA were analyzed, using proliferating cell nuclear antigen (PCNA), and compared with 24 non-depressed adenomas (NDA), 12 non-neoplastic mucosa and 12 adenocarcinomas. The DA had a characteristic architecture when compared with the NDA, as demonstrated by a crowded collection of adenomatous tubules with small diameters. The adenomatous tubules tended to occupy the full thickness of the lamina propria at the center with superficial growth to the periphery. The PCNA-positive cells were mostly restricted to the lower half of the crypts in the non-neoplastic mucosa, and were distributed predominantly across the upper half area of the crypts in both the DA and NDA, whereas they were randomly distributed across any area in the adenocarcinomas. The mean labeling index of PCNA in the DA (43.2%) was significantly higher than that in the non-neoplastic mucosa (26.5%) and NDA (29.3%), but lower than that in the intramucosal component of the adenocarcinomas (70.0%). The DA should be seriously considered as a precancerous lesion because of its unusual histologic architecture and high proliferative activity.     

Expression of proliferating cell nuclear antigen (PCNA) in dysplasia of the bronchial epithelium

Proliferating cell nuclear antigen (PCNA) is expressed in cells in the cell cycle and has been studied as a marker of proliferation in lung and other tumours. We have noted immunocytochemical differences in PCNA expression between normal and neoplastic bronchial cells. As bronchial dysplasia is considered preneoplastic, we have examined PCNA expression in this condition. PCNA staining in 47 cases of bronchial dysplasia and 32 samples of normal bronchial epithelium was compared. Of the dysplasias, three were mild, 11 moderate, and 33 severe. A significant increase in PCNA counts over normal epithelium was seen only in moderate and severe dysplasias. In dysplasia, mitotic indices showed a significant positive correlation with the percentage of PCNA-positive cells. We conclude that in moderate and severe dysplasias there is an increase in the number of cells expressing PCNA and undergoing division, indicating abnormal growth control.     

P53 and proliferating cell nuclear antigen (PCNA) expression in non-tumoral liver diseases

The tumor suppressor gene p53 is known to be involved in the negative regulation of cell growth. Proliferating cell nuclear antigen (PCNA), which is a nuclear protein and a component of the DNA replication process, is also involved in growth regulation. Both have been studied as progression markers in various tumors including hepatocellular carcinoma. In the present study, the aberrant p53 protein and PCNA expressions in non-tumoral liver diseases were investigated. Using monoclonal antibodies anti-p53 (D07-DAKO) and anti-PCNA (PC10-DAKO), 149 samples were stained, including 10 normal and 10 tumoral control liver tissues. p53 Overexpression was detected in 52 specimens (35%) whereas PCNA positivity was found in 96 (64%). There were 21 different pathological entities but most of the positive samples could be grouped into four types of diseases; namely, non-specific reactive hepatitis, steatohepatitis, chronic hepatitis and cirrhosis. Statistical analyses performed on these groups revealed that p53 positivity was found to be significantly higher in steatohepatitis (P < 0.05), while PCNA positivity did not show any statistical significance. The number of samples showing both p53 and PCNA positivity was 42 but their coexistence was not found to be significant. Certain cytological alterations like nuclear pleomorphism, steatosis and cholestasis, in addition to necroinflammatory activity, were evaluated for their possible impact on p53 and/or PCNA positivity. Necroinflammatory activity in steatohepatitis and steatosis in chronic hepatitis was found to be significant for p53 positivity (P < 0.05). In contrast, nuclear pleomorphism in non-specific reactive hepatitis was found to be significant for PCNA positivity (P < 0.05).     

Haemangiopericytomas: the prognostic value of immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA)

Forty-two cases of haemangiopericytoma were studied retrospectively using immunohistochemical staining with PC10, a monoclonal antibody to PCNA. The percentage of tumour cells with positive staining for PCNA was found to correlate well with histological grading. Clinical follow-up data were available in 25 adults and showed no known deaths in 11 cases with a low proportion (less than 14%) of positive cells. Out of 14 cases with a high number (greater than or equal to 14%) of positive cells, seven patients are known to have died, two had metastases, and in a further two there have been multiple recurrences of tumour. DNA flow cytometry was performed on 26 cases but this showed no correlation with PC10 staining or clinical outcome. Staining with PC10 may be of particular value in the identification of patients at greatest risk of rapid tumour metastasis and early death.     

Assessment of proliferating cell nuclear antigen expression in precursor stages of gastric carcinoma using the PC10 antibody to PCNA

Immunohistochemistry using the PC10 antibody to proliferating cell nuclear antigen (PCNA) was applied to archival material from mucosa adjacent to gastric carcinoma ('normal', hyperplasia, complete and incomplete intestinal metaplasia and dysplasia) and non-cancer controls (normal and complete intestinal metaplasia). Overall, increased PCNA indices, with expansion and altered location of the proliferative zones, were observed in carcinoma fields and compared with controls ( P ≤0.001). These differences were particularly significant in 'normal' mucosa far from carcinoma as compared with normal in controls ( P ≤0.001). In carcinoma 'fields' distinct patterns of PCNA expression were noted in complete and incomplete intestinal metaplasia. Similarly, in dysplastic lesions high PCNA indices were present either throughout the gland or found predominantly in the upper compartment. We conclude that these differences in PCNA index and staining patterns might prove useful in monitoring the evolution of the disease in the follow-up of patients at risk of developing gastric cancer.     

The significance of proliferating cell nuclear antigen in human trophobiastic disease: an immunohistochemical study

The expression of proliferating cell nuclear antigen (PCNA) in human trophobiastic disease was assessed immunohistochemically in tissue from 29 spontaneous abortions, 33 partial moles, 40 complete moles and 23 chorio carcinomas using the monoclonal antibody PC ID. PCNA immunoreactivity occurred predominantly in the cytotrophoblasts in each of the four types of tissues. Quantitative analysis showed that the choriocarcinoma group gave a statistically significant higher PCNA index than the other three. There was no significant difference between the groups of spontaneous abortion, partial or complete mole. Sixteen of the 73 patients with partial and complete moles developed persistent gestational trophobiastic disease and there was no significant difference between the patients requiring chemotherapy and those who did not. We conclude that choriocarcinoma has a significantly higher PCNA proliferative index whilst hydatidiform moles cannot be distinguished from abortions by such analysis. The PCNA index does not appear to be useful in predicting the progression of molar pregnancies to persistent trophobiastic diseases.     

Enhanced polymer one-step staining (EPOS) for proliferating cell nuclear antigen (PCNA) and Ki-67 antigen: Application to intra-operative frozen diagnosis

Enhanced polymer one-step staining (EPOS) is a novel, highly sensitive one-step immunostaining method. This simple and rapid technlque was applied to intra-operattve frozen diagnosis. The markers of choice were proliferating cell nuclear anmen (PCNA) and Ki-67 antigen. These cell prollferation markers were both identifiable in fresh frozen see tions of the human tonsil In approximately 7 min. The suitable staining sequences are as follows. Frozen sections prepared using 3-aminopropyitimethoxysilane-cpated glass slides are immediately fixed, without air drying, for 15s in a mixture of 50% formalin and 50% methanol for PCNA, and in 10% formalln for Ki-67 antigen. After a brief rinse in phosphate-buffered saline (PSS), sections are incubated with the EPOS antibody for 3 min, followed by PBS rinse for 1 min. The peroxidase activity is visualized in diaminobenzidine-H₂O₂ solution containing 10mmol/L imidazole for 2 min. After a light rinse in tap water, the nuclei are briefly counterstained with 5% methyl green. When necessary, endogenous peroxi-dase blockage in 1% periodic acid solution for 1 min is added before the EPOS antibody incubation. This procedure is applicable to frozen sections of gastric cancers, malignant lymphomas, and brain, liver and peritoneal lesions in which differential diagnosis between benignancy and malignancy was required.     

Proliferative activity of calcifying odontogenic cysts as evaluated by proliferating cell nuclear antigen labeling index

The calcifying odontogenic cyst (COC) presents with diverse hlstologlcal features; thus, several subclasslfl-cations have been proposed. To evaluate the slgnlficance of the various histological features and subtypes of COC from the perspectlve of proliferative activity, the proliferating cell nuclear antigen (PCNA) labellng index (LI; the percentage of positive nuclei) was assessed immunohistochemlcally in 25 cases of COC (21 benign and four malignant). All of the benign cases were of the cystic variety and further subclas-sified into non-proliferative subtype (NPS; four cases); proliferative subtype (PS; eight cases); and COC associated with odontoma (COCaO, nlne cases). The PCNA U of the mallgnant COC (65.2 ± 5.6) was slgnlflcantly higher than that of the benlgn COC (11.6 ± 9.0; P = 0.002). Non-proliferative subtype (6.8 ± 2.8) showed the lowest PCNA LI and PS (17.2 ± 11.2) the highest of among the three subtypes of benign cystic COC (P = 0.028). In nine cases of COCaO, six showed epithelial lining of the non-proliferative type as NPS and the other three had lining wlth proliferative features as PS. The PCNA LI of the latter COCaO group (14.3 ± 6.6) was significantly higher than that of the former (6.1 ± 4.3; P = 0.05), as Seen between PS and NPS. These results demonstrate that PCNA LI is a possible parameter for differentiating mallgnant COC from benign COC and, whatever the subtypes, the proliferative features In the lining are the main factor influencing the prollferatlng actlvity of COC.     

The assessment of proliferating cell nuclear antigen (PCNA) immunostaining in primary gastrointestinal lymphomas and its relationship to histological grade, S + G2 + M phase fraction (flow cytometric analysis) and prognosis

PCNA is a nuclear protein that is synthesized in late G1 and S phases of the cell cycle and is, therefore, correlated with the cell proliferative state. A new monoclonal antibody (PC10) to genetically engineered PCNA has been shown to label proliferating cells in formalin-fixed paraffin-embedded normal human tissues. Previous studies in lymphomas, using various markers of cell proliferation, have shown a strong correlation between indices of cell proliferation and histological grade. These studies have shown that within each histological subtype there is often a wide range of proliferative indices and that these may be of some prognostic significance. Thirty-one gastrointestinal lymphomas were studied. Our results show that there is a good correlation between PC10 index and histological grade of tumour (0.01 P greater than P greater than 0.001) and also a significant relationship between PC10 index and S+G2+M phase fraction as measured by flow cytometric analysis (r2 = 0.62; P less than 0.01). Twenty-three cases were available for survival analysis. In these cases a high PC10 score correlated with poor survival (P = 0.04). Based on this series, it appears that there is a significant relationship between PC10 index and histological grade, and between PC10 index and S+G2+M phase as measured by flow cytometric analysis. In addition, our results suggest that a high PC10 index is an adverse prognostic factor in primary gastrointestinal lymphoma.     

人胚胎发育过程中肝细胞增殖细胞核抗原表达水平的研究

目的　研究人胚胎发育过程中肝细胞增殖细胞核抗原 (PCNA)的表达水平。方法　采用免疫组织化学方法 ,检测 2～ 8个月胚胎肝细胞PCNA表达水平。结果　胚胎肝细胞PCNA的表达水平随月份增强。结论　胚胎肝细胞PCNA的表达水平的与胚胎发育过程中肝细胞的功能有着密切联系     

增殖细胞核抗原阳性细胞在幼年大鼠前脑的分布

目的　探讨幼年大鼠前脑内是否存在增殖细胞。方法　用增殖细胞核抗原 (PCNA)单克隆抗体PC10免疫组化研究。结果　PCNA阳性反应部位分两类 :一类为圆形或卵圆形深染颗粒 ,具有核的形态和大小 ,主要分布于吻侧迁移流、室管膜下带和部分血管壁 ;散在分布于尾壳核、运动皮质、隔区和斜角带 ;有时见“镜影核” ,主要存在于尾壳核 ;另一类为整胞体染色 ,见于室管膜、室管膜下带和吻侧迁移流。结论　幼年大鼠前脑内存在增殖细胞     

增殖细胞核抗原在实验性脑出血大鼠脑组织中的表达及其意义

研究实验性脑出血时大鼠脑组织中增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达及其意义。将成年SD大鼠随机分为正常组、假手术组和脑出血组;脑出血组大鼠通过立体定向术向脑内注入自体动脉血制成脑尾壳核出血模型,并按不同的再喂养时间(1、3、7、14及30d)分为5个亚组。运用RT-PCR检测PCNA mRNA表达水平,采用免疫组化单标和双标染色观察PCNA阳性细胞的分布,增殖水平及分化情况。RT-PCR结果显示,PCNA mRNA表达在脑出血后14d达高峰。免疫组化单标结果表明,PCNA阳性细胞主要分布于出血灶边缘、脉络丛、室管膜下层、胼胝体和额顶皮质等处。PCNA阳性细胞数在脑出血后1d开始增加,14d达高峰,随后渐下降,但30d时仍明显高于正常组和假手术组。免疫组化双标结果显示在脑出血侧纹状体和额顶皮质可见PCNA/GFAP双标阳性细胞,在额顶皮质可见PCNA/NF-200双标阳性细胞。以上结果提示,脑出血可诱导PCNA阳性细胞增殖、分化,并向出血灶周边区聚集,这可能是脑出血后神经功能恢复的重要物质基础。     

增殖细胞核抗原在唾腺肿瘤中的表达及其临床意义

目的：探讨唾腺肿瘤增殖细胞核抗原（ＰＣＮＡ）的表达和肿瘤恶性程度的关系。方法：用ＰＣＮＡ单抗对７７例唾腺肿瘤作免疫组化研究。结果：唾腺肿瘤ＰＣＮＡ阳性程度与肿瘤的良恶性、恶性瘤的分级、肿瘤的复发、转移密切相关。结论：ＰＣＮＡ是肿瘤增殖良好的标志物。唾腺肿瘤ＰＣＮＡ阳性程度，可作为评价唾腺肿瘤恶性程度的指标     

Preliminary results of prognostic significance of proliferating cell nuclear antigen expression in advanced primary larynx carcinomas and lymph node metastases

Introduction

The aim of this study was to investigate the prognostic significance of proliferating cell nuclear antigen (PCNA) expression in laryngeal carcinoma in relation to clinicopathological features. Special emphasis was placed on examining the relationship of PCNA expression in the primary tumour and PCNA expression in corresponding lymph node metastases obtained from the same patients.

Material and methods

The study included 60 patients with advanced larynx carcinoma who had received treatment and follow-up for at least 5 years. Sixty laryngeal carcinoma specimens and metastatic lymph nodes from 24 patients were examined for immunohistochemical PCNA expression.

Results

The percentages of PCNA positive cells were significantly higher in the primary tumours which developed lymph node metastases than in those without metastases. The fraction of PCNA immunolabelled cells in metastatic lymph nodes increased significantly when compared with the PCNA positive cell score in their corresponding primary tumours obtained from the same patient. There was a significant difference in PCNA index score in primary tumours between the group of patients who survived a 5-year period and those who died within 5 years after treatment.

Conclusions

Our data demonstrate that a high proliferation index in primary larynx tumours is retained and increased in corresponding lymph node metastases. Measurement of the fraction of cancer cells stained for PCNA in primary larynx carcinomas can be helpful in selecting tumours with high aggressiveness potential that are more likely to develop neck metastases and thereby in identifying patients who need elective lymph node dissection or additional treatment.     

大黄酸对受损肠黏膜上皮增殖细胞核抗原及PARP降解产物表达的影响

目的:探讨大黄酸对于受损伤的肠黏膜上皮增殖细胞核抗原(PCNA)及细胞凋亡的标志蛋白PARP降解产物(cleaved-PARP)表达的影响。方法:SD雌性大鼠随机分成正常对照组、肠黏膜损伤组、大黄酸治疗组和大黄酸预防组。用牛血清白蛋白+脂多糖+四氯化碳联合用药构建肠黏膜损伤模型,大黄酸预防组和大黄酸治疗组大鼠分别在建模前后用大黄酸悬浊液灌胃。采用免疫组织化学及图像分析仪显示和分析回肠上皮PCNA及cleaved-PARP表达情况。结果:与正常对照组比较,损伤组PCNA表达减少,cleaved-PARP表达增加。与黏膜损伤组比较,大黄酸预防组和治疗组PCNA表达均增加,cleaved-PARP表达均减少,大黄酸预防组效果更显著。结论:大黄酸能增强受损伤的肠黏膜上皮细胞PCNA的表达,抑制cleaved-PARP的表达,促进肠上皮的生长,抑制上皮细胞凋亡,从而为肠黏膜损伤产生保护和修复作用。     

Temporal and histologic relationships of proliferating cell nuclear antigen and human papillomavirus type 11 in the mouse xenograft system

Proliferating cell nuclear antigen (PCNA) is an accessory protein of DNA polymerase delta. This protein is associated with cell cycle progression and can be detected in the replicating cells of normal tissues. Condylomata acuminata are benign epithelial tumors caused by infection with human papillomaviruses and are characterized by abnormal cell proliferation. The athymic mouse xenograft model of HPV 11 infection was used to test the hypothesis that PCNA is induced early in the course of HPV 11 infection and to study the temporal and histologic relationships between detection of PCNA and HPV DNA. Human foreskin tissue was infected with HPV 11 and implanted under the renal capsules of 10 athymic mice. Pairs of mice were sacrificed every week beginning four weeks after implantation. HPV DNA was detected in sections of foreskin implants by in situ hybridization. PCNA was as or more abundant in implants removed at earlier time points than at later time points, whereas HPV DNA became increasingly more abundant with time. PCNA was detected only in basal cells in areas of histologically normal epithelium that were also negative for HPV DNA. In contrast, PCNA was present throughout the epithelium in regions that were HPV DNA-positive. HPV DNA was detected only in differentiated epithelial cells in implants removed at all five time points, but in HPV DNA-positive regions, PCNA was detected with equal intensity in differentiated and undifferentiated cells. The foci of PCNA-positive cells were well demarcated and were larger than, but included, the foci of HPV DNA-positive cells. PCNA may be induced maximally in differentiated epithelium by HPV 11 prior to significant HPV DNA replication. © 1996 Wiley-Liss, Inc.     

流行性出血热肾组织中增殖细胞核抗原、波形丝蛋白的表达及其意义

目的　研究流行性出血热 (EHF)肾组织中增殖细胞核抗原 (PCNA)和波形丝蛋白 (vimentin)的表达及意义。方法　应用多重PAP免疫组化方法 ,对 17例EHF尸检肾组织中PCNA和vimentin的表达进行观察。结果　EHF尸检肾组织PCNA的阳性率为 6 4 71% ,集合管的增殖指数显著大于远曲小管 (P <0 0 1) ,低血压休克期患者远曲小管和集合管上皮细胞vimentin呈强阳性表达 ,相同部位PCNA也呈阳性 ,PCNA的阳性强度与局部病变的程度相一致。结论EHF患者急性肾功能衰竭的早期就存在损伤肾小管上皮细胞的再生、增殖和分化 ,这些变化在EHF肾损伤的修复反应中具有重要的意义