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。     

PCNA及bcl-2与caspase-3在卵巢上皮性交界性肿瘤中的表达及意义

目的:探讨增殖细胞核抗原(PCNA)、bcl-2与caspase-3在卵巢上皮性交界性肿瘤中的表达及临床意义.方法:选取天津医科大学附属肿瘤医院病理科存档的卵巢上皮性交界性肿瘤40例,采用免疫组化SP法检测PCNA、bcl-2与caspase-3在肿瘤组织中的表达,并与良性、恶性肿瘤进行比较.结果:在卵巢交界性肿瘤中1)PCNA阳性率为72.5%,明显高于良性肿瘤(47.6%),低于恶性肿瘤(89.6%,P＜0.05);bcl-2与caspase-3的阳性率为60.0%和72.5%,而良性与恶性肿瘤分别为61.9%和76.2%、86.2%和44.8%,二者在恶性肿瘤中的表达与良性、交界性有显著差异(P＜0.05).2)PCNA与bcl-2的表达存在相关性,其协同表达率为52.5%,与良性(28.6%)、恶性肿瘤(75.9%),存在显著性差异(P＜0.05);PCNA、bcl-2与caspase-3的协同表达率为72.7%,良性与交界性肿瘤明显高于恶性肿瘤(P＜0.05).3)仅bcl-2与组织学类型有关,浆液性肿瘤的阳性率明显高于粘液性(P＜0.01);PCNA、caspase-3与临床病理参数无关.结论:PCNA与bcl-2任一高表达尤其协同表达,并伴caspase-3低表达是卵巢交界性肿瘤恶性潜能增加的标志,应密切随访.     

P57KIP2和PCNA在人脑胶质瘤中的表达及其意义

目的研究有丝分裂抑制因子P57KIP2、增殖细胞核抗原PCNA蛋白在人脑胶质瘤中的表达及其意义.方法免疫组化S-P法检测46例脑胶质瘤中P57KIP2与PCNA蛋白的表达情况.结果 P57KIP2蛋白在脑胶质瘤中的表达阳性率分别为34.8%,显著低于正常脑组织的阳性率75%(P＜0.01);PCNA蛋白在脑胶质瘤中的表达阳性率为60.9%,显著高于正常脑组织的20%(P＜0.01).两者的表达率均与肿瘤的恶性程度(P＜0.05,P＜0.05)及两年生存率有关(P＜0.01,P＜0.05).P57KIP2与PCNA的表达密切相关(P＜0.01,rs=-0.537).结论 P57KIP2基因的表达水平与肿瘤细胞增殖活性有密切的关系,其表达水平的改变在肿瘤生长中起关键作用.P57KIP2和PCNA的联合检测有利于更准确地判断细胞的增殖活性和预后.     

人脑膜瘤血管内皮生长因子表达及生物学意义

[目的]研究血管内皮生长因子(VEGF)在人脑膜瘤中的表达及其生物学意义.[方法]采用免疫组织化学方法检测51例脑膜瘤(WHO分级良性38例,非典型11例,恶性2例)VEGF蛋白的表达水平和微血管密度(MVD).[结果]良性脑膜瘤VEGF阳性表达率86.8%(33/38),不典型、恶性脑膜瘤VEGF阳性表达率为84.6%(11/13)(P＞0.05).而3例正常脑膜组织未见VEGF表达(P＜0.05).良性、非典型及恶性脑膜瘤的MVD分别为131.08±115.93和145.12±99.21(P＞O.05),VEGF表达阴性的脑膜瘤其MVD为88.25±59.86,VEGF表达呈 、 、 的MVD为102.25±149.55,108.12±54.43,172.36±118.58,两者表达成正相关(r=O.45,P＜0.05).VEGF表达与脑膜瘤的侵袭性、脑浸润性无关.[结论]VEGF在脑膜瘤的血管形成中起重要作用,可能参与脑膜瘤的形成,但与脑膜瘤的良性向非典型转变、脑浸润性、侵袭性等生物学特性无关.     

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.     

IGF-Ⅰ和IGF-ⅠR在膀胱癌组织中表达的意义

背景与目的:胰岛素样生长因子(insulin-like growth factors,IGFs)是一类具有促进细胞增殖、分化等多种生物学活性的多肽生长因子,研究表明其参与多种恶性肿瘤的发生、发展过程.本研究检测IGF-Ⅰ及其受体IGF-ⅠR和增殖细胞核抗原(proliferation cell nuclear antigen,PCNA)在正常膀胱组织和膀胱癌组织中的表达,评价IGF-Ⅰ和IGF-ⅠR的临床意义.方法:应用免疫组织化学方法检测IGF-Ⅰ、IGF-ⅠR和PCNA在88例膀胱癌和12例正常膀胱组织中的表达,同时对IGF-Ⅰ和IGF-ⅠR表达与膀胱癌病理分级、临床分期、预后及PCNA表达之间的关系进行分析.结果:膀胱癌组织中IGF-Ⅰ和IGF-ⅠR阳性率分别为73.9%、59.1%,均显著高于正常膀胱组织的33.3%、16.7%(P＜0.05).膀胱癌中两者呈相关表达且均与PCNA指数密切相关(P＜0.05).IGF-Ⅰ表达与肿瘤复发之间关系密切(P＜0.05),IGF-ⅠR表达则与肿瘤分级、分期和复发关系密切(P＜0.05).结论:IGF-Ⅰ与肿瘤复发有关,IGF-ⅠR表达与肿瘤分级、分期和复发有关.     

SHH、EGFR和PCNA蛋白在胰腺癌组织中的表达及其意义

背景与目的:SHH(sonic hedgehog)信号通路为胚胎发育过程中调节细胞间相互作用的重要信号通路,表皮生长因子受体(epidermal growth factor receptor,EGFR)具有调节细胞增殖、分化的作用,增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)是反映细胞增殖的指标.本研究的目的是探讨SHH、EGFR和PCNA蛋白在胰腺癌组织中的表达及其意义.方法:采用免疫组化方法检测49例胰腺癌组织及癌旁组织中SHH、EGFR蛋白和PCNA的表达情况,并分析其相关性.结果:SHH和EGFR蛋白在胰腺癌组织中的阳性率分别为79.6%和73.5%,与癌旁组织(14.3%和16.3%)相比,差异有统计学意义(P＜0.05).SHH和EGFR蛋白表达与患者年龄、肿瘤大小、组织学类型和肿瘤部位等均无关(P＞0.05),而与淋巴结转移状况和TNM分期有关(P＜0.05).胰腺癌组织中83.7%呈PCNA蛋白高表达,与癌旁组织(20.4%)相比,差异有统计学意义(P＜0.05).Spearman相关分析显示,SHH与EGFR蛋白表达呈正相关关系(r1=0.232,P＜0.05).PCNA蛋白表达与SHH和EGFR蛋白表达均呈正相关性(r2=0.412,P＜0.05;r3=0.186,P＜0.05).结论:SHH和EGFR信号通路在胰腺癌组织中均呈激活状态,并且与胰腺癌细胞的增殖活性相关.     

乳腺癌组织中PCNA和Cath-D的表达及相关性研究

目的:探讨Cath-D 、PCNA 在乳腺癌中表达的意义及相关性.方法:应用免疫组化S-P 法检测49例乳腺癌中Cath-D 、PCNA 的表达情况,并与35 例乳腺良性病变进行对照分析.结果:乳腺良性病变Cath-D 、PCNA 的阳性率分别为17.1 %(6/ 35) 、28.6 %(10/ 35) .乳腺癌Cath-D 、PCNA 的阳性率分别为53 %(26/ 49) 、73.5 %(36/ 49) ,差异具有统计学意义(P＜ 0.05) .乳腺癌Cath-D 的表达与年龄无关(P＞ 0.05) ,与组织学分级相关(P＜ 0.05) ;PCNA的表达与年龄、组织学分级均无关(P＞ 0.05) .乳腺癌Cath-D 、PCNA 的表达呈正相关(P＜ 0.05) .结论:Cath-D 、PCNA 表达异常在乳腺癌的发生、发展中具有重要的作用,两者具有相互作用.Cath-D 、PCNA 可用于良、恶性乳腺疾病的鉴别,对乳腺良性病变的恶性转化有一定的预兆性.     

Ley 抗原在卵巢上皮性肿瘤中的表达及意义

目的:探讨卵巢癌组织ley抗原的表达及其临床意义.方法:采用免疫组织化学SP法检测恶性、交界性、良性卵巢上皮肿瘤及正常卵巢组织中ley抗原的表达,并分析其与卵巢癌生物学特性之间的关系.结果:ley抗原在恶性卵巢上皮性癌中的阳性表达率为75.47%(40/53),明显高于交界性卵巢上皮性肿瘤(47.06%)及良性卵巢上皮性肿瘤(42.86%)(P均＜0.05).正常卵巢组织中未检出ley抗原的表达.晚期卵巢上皮性癌的ley抗原的阳性表达率为84.21%,明显高于早期卵巢上皮性癌(53.33%),(P＜0.05).结论:ley抗原与卵巢上皮性癌的发生、发展相关.ley抗原的表达可作为反映卵巢癌恶性潜能的一项新的指标.     

HLA-G基因在星形细胞肿瘤中的表达及意义

目的分析HLA-G mRNA在星形细胞肿瘤的表达情况,探讨其表达是否与肿瘤的恶性转化有关.方法应用逆转录聚合酶链反应(RT-PCR)技术检测49例星形细胞肿瘤、11例脑膜瘤、7例脑损伤组织中HLA-G mRNA表达.结果7例正常脑组织均为阴性,而11例脑膜瘤中仅有2例表达HLA-G mRNA,其中1例为非典型脑膜瘤.49例星形细胞肿瘤中,6例Ⅰ级病例中,未检测到有HLA-G mRNA表达;20例Ⅱ级病例中阳性表达HLA-G mRNA有6例(30%);16例Ⅲ级病例中有14例(87.5%)阳性表达;7例Ⅳ级有6例(85.7%)阳性表达.HLA-G在星形细胞肿瘤中以HLA-G3 mRNA表达为主.星形细胞肿瘤HLA-G mRNA阳性表达率明显高于脑膜瘤(P＜0.05)和正常脑组织(P＜0.01),高度恶性星形细胞肿瘤HLA-GmRNA阳性表达率高于脑膜瘤(P＜0.01).结论HLA-G基因在星形细胞肿瘤有表达,且表达情况与病理分级有关.HLA-G基因表达可能参与胶质瘤的免疫耐受.     

No prediction of recurrence of meningiomas by PCNA and Ki-67 immunohistochemistry

Immunohistochemistry for the expression of the proliferation markersproliferating cell nuclear antigen (PCNA) and Ki-67 wasstudied in 16 non recurring meningiomas, 11 meningiomasrecurring as benign tumors, 6 recurring as atypicalmeningiomas and in 9 recurring as malignant meningiomas.Non recurring meningiomas were defined in this studyas tumors without recurrence at least 8 yearsafter surgery. In addition 16 benign recurrences, 14atypical- and 12 malignant meningiomas were studied. Ineach group great variation of labeling indices (LI)= per cent of tumor cells labeled wasobserved, especially of PCNA LIs. The non recurringmeningiomas displayed lower mean LI for PCNA andKi-67 than did the recurring meningiomas of allgroups but the differences were not statistically significant.The same pattern was seen when totally resectedtumors were studied alone. Benign-, atypical-, and malignantmeningiomas had labeling indices that were related tothe grade of malignancy. Only PCNA LIs ofatypical- and malignant meningiomas were statistically significantly higherthan PCNA LIs of non recurring meningiomas. Thestudy indicates that PCNA and Ki-67 are ofminor value as predictors of recurrence of benignmeningiomas.     

Proliferative potential of human meningiomas of the brain. A cell kinetics study with bromodeoxyuridine

Twenty patients with intracranial meningiomas were given a 1-hour intravenous infusion of bromodeoxyuridine (BrdU), 200 mg/m2, at the time of surgery to label tumor cells in the DNA synthesis phase (S phase). The excised tumor specimens were fixed with 70% ethanol, embedded in paraffin, sectioned, and stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody as the first antibody. The BrdU labeling index (LI), or S-phase fraction, was determined by counting the number of BrdU-labeled cells in the tissue sections. The average LIs for nonmalignant (11 cases) and histologically malignant meningiomas (seven cases) were 0.45% and 3.9% respectively (P less than 0.05). Two hemangiopericytic variants showed average LIs of 0.53% and 4.1%. Four of seven malignant meningiomas and both hemangiopericytomas were recurrent tumors. Nine of 20 meningiomas had an LI greater than 1%, and six of those nine (67%) were recurrent. Thus, meningiomas with an LI greater than 1% appear to grow faster and recur more frequently than those with LIs less than 1%; the higher LI may indicate biological malignancy. The measurement of BrdU LI in meningioma may prove valuable in establishing the diagnosis of "malignant meningioma."     

Implication of telomerase activity and alternations of telomere length in the histologic characteristics of intracranial meningiomas

BACKGROUND: Telomerase activity and telomere length have been shown to be involved in the control of cell proliferation and regulation of cell senescence. The expression of telomerase activity may endow cells with the capacity of unlimited proliferation and immortality. The authors examined the telomerase activity and telomere length of intracranial meningiomas to determine the relation between the results and the clinicopathologic behavior of these tumors. METHODS: Sixty-two specimens of meningiomas including 13 atypical and malignant tumors were used in this study. Telomerase activity was measured with polymerase chain reaction and enzyme-linked immunosolvent assay. Telomere length was measured by detecting the terminal restriction fragments using Southern blots. RESULTS: Detectable telomerase activity was found in 4 of 13 (30.8%) malignant or atypical meningiomas and only 1 in 49 benign meningiomas (P = 0.006). Elongated telomere length was measured in 6 of 13 (46.1%) patients with malignant or atypical meningiomas and only 1 of 48 (2.1%) in those with benign tumors (P = 0.0002). Three of 4 (75%) of malignant or atypical meningiomas with detectable telomerase activity revealed shortened telomere length, and all tumors with elongated telomere length displayed undetectable telomerase activity. The percentage of malignant or atypical meningiomas with detectable telomerase activity or elongated telomere were significantly higher (76.9%) than that of benign tumors (4.0%). The proliferative index was calculated as the percentage of tumor cell nuclei immunoreactive for Ki-67 to total tumor nuclei. The mean values of proliferative index in benign, atypical, and malignant meningiomas were 1.2, 11.0, and 30.0, respectively. CONCLUSIONS: The results indicate that telomerase activation may be a critical step in the pathogenesis of malignant or atypical meningioma. Elongation of the telomere length also implicates the high potential for malignant behavior in these tumors.     

Proliferative potential of meningiomas evaluated by proliferating cell nuclear antigen expression

Meningiomas are principally benign in nature. Some meningiomas, however, grow fast or recur even after total removal. The biological behavior of meningiomas often can not be predicted from conventional histopathological studies. A monoclonal antibody against proliferating cell nuclear antigen (PCNA) was used to investigate the usefulness of the PCNA index as a parameter to estimate the proliferative activity of meningiomas. Fifty-two meningiomas were examined. The mean PCNA index of recurrent meningiomas (3.37±0.92%) was significantly higher than that of non-recurrent meningiomas (1.12±0.51%) (p <0.005). The PCNA indices of recurrent cases were all higher than 2.0%. A semilog linear regression analysis between tumor doubling time and PCNA index showed a significant correlation (r=0.90, p < 0.05). An inverse linear correlation between PCNA index and interval to recurrence was observed (r=0.62, p < 0.05). A good linear correlation was also shown between PCNA index and BUdR labeling index (r = 0.88, p < 0.01). The results of this study suggest that, providing the methods of tissue processing, immunostaining and counting of positive nuclei are unified, the PCNA index is a useful parameter for estimating the biological behavior of meningiomas.     

脑膜瘤Ki—67MIB—1的表达及其诊断价值

目的　研究肿瘤细胞增殖活性及其在诊断脑膜瘤中的价值。　方法　应用Ｋｉ６７ ＭＩＢ１ 免疫组织化学方法,检测其在脑膜瘤中的表达。　结果　良性脑膜瘤的Ｋｉ６７ ＭＩＢ１ 平均指数为２４５％ ,非典型脑膜瘤为５５ ％ ,恶性脑膜瘤为１１２ ％ 。良性脑膜瘤与非典型脑膜瘤比较差异有显著性（ Ｐ＜ ０００１）,非典型脑膜瘤与恶性脑瘤比较差异有显著性（ Ｐ＜ ０００１） 。核分裂与Ｋｉ６７ ＭＩＢ１ 表达呈相关性（ｒ＝ ０７７９ ,Ｐ＜０００１）。　结论　Ｋｉ６７ＭＩＢ１ 染色有助于脑膜瘤的正确诊断。     

Bcl-2、Bax、Bcl-XL在脑膜瘤细胞中的表达及其临床意义

目的 观察凋亡调节蛋白的表达与脑膜瘤级别和复发的关系。方法 用LSAB免疫组织化学方法对80例脑膜瘤细胞中凋亡调节蛋白Bcl-2、Bax、Bcl-XL的表达进行分析。结果 恶性组Bcl-2瘤蛋白阳性率(88％)明显高于良性组(37％,P<0.05)。分别比较良性组、非典型组、恶性组中Bax、Bcl-xL癌蛋白表达阳性率,无显著性差异(P>0.05)。而Bel-2+Bcl-XL/Bax与脑膜瘤级别有统计学相关性(P<0.01)。非复发组、复发组首次手术组、再次复发组中Bcl-2、Bax、Bcl-XL癌蛋白阳性率两两比较均无显著性差异(P>0.05)。结论 Bcl-2、Bax、Bcl-XL在脑膜瘤发生中起调节作用,Bcl-2+Bcl-XL/Bax是脑膜瘤生物学行为的有效检测法。     

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。     

Statin immunolocalization in human brain tumors. Detection of noncycling cells using a novel marker of cell quiescence.

Surgical specimens of 35 human brain tumors were examined with a novel monoclonal antibody, S-44, immunoreactive to statin, a nuclear protein specifically expressed in quiescent (noncycling) G0-phase cells. Benign tumors typically were statin positive with labeling indices (LI) between 22% and 96%: acoustic schwannomas (n = 3, mean = 29.9 +/- 19.4%); meningiomas (n = 4, mean = 59.0 +/- 15.1%); pituitary adenomas (n = 3, mean = 79.9 +/- 28.2%), and an epidermoid cyst (41.0%). By contrast, the statin LI of 18 of 24 (75%) malignant brain tumors was less than or equal to 2%: medulloblastomas (n = 7, mean = 0.3 +/- 0.2%); anaplastic astrocytomas (n = 3, mean = 1.6 +/- 2.7%); glioblastomas (n = 10, mean = 10.3 +/- 14.4%); metastatic carcinomas (n = 3, mean = 3.0 +/- 4.6); and a germinoma (0.2%). The vascular endothelium among diverse tumors typically was statin positive. All 21 tumors with a statin LI less than 10% were malignant, and all nine tumors with a statin LI greater than 40% were benign. The statin LI of benign tumors (n = 11, mean = 55.1 +/- 26.7%) was significantly higher than that of the malignant tumors (n = 24, mean = 5.2 +/- 10.5%, P less than 0.001). The absence of statin expression is a new way to determine the malignancy of human brain tumors. The statin LI may be useful to guide the prognosis and treatment of individual patients. The mechanisms that control statin expression are important in therapy seeking to shift the proliferating, cycling cells to the quiescent, G0 compartment.