含复方中药大鼠血清对人卵巢癌新鲜实体瘤细胞增殖影响的研究

目的探讨复方中药治疗卵巢癌的作用机制。方法应用中药血清药理学的实验方法,利用大鼠制备含药血清,采用细胞排染法和3H掺入法观测含药血清对39例卵巢癌新鲜实体瘤细胞增殖的作用。结果细胞排染法检测低、中、高浓度含药血清对卵巢癌新鲜实体瘤细胞生长的抑制率在上皮性肿瘤中分别为(13.36±2.38)%、(27.68±3.76)%和(43.24±4.54)%,在性索间质肿瘤中分别为(9.53±2.16)%、(21.32±3.09)%和(38.27±3.52)%,在生殖细胞肿瘤中分别为(8.88±1.98)%、(19.08±3.62)%和(37.25±3.46)%。在各病理类型中,随含药血清浓度的增加,抑制率增高,P<0.05。在不同浓度含药血清中,对卵巢上皮性癌细胞增殖的抑制率均明显高于对生殖细胞和性索间质细胞肿瘤细胞增殖的抑制率,P<0.05。经空白血清及低、中、高浓度含药血清处理的卵巢癌新鲜实体瘤,3H掺入法检测的的cpm值在上皮性肿瘤中分别为526.24±36.68、445.63±36.72、378.21±37.82和302.16±32.36;在性索间质肿瘤中分别为530.63±36.72、508.87±45.86、468.93±46.27和403.11±37.54;在生殖细胞肿瘤中分别为523.21±37.82、501.11±44.67、447.22±46.58和381.79±37.2。同一种卵巢肿瘤病理类型中,含药血清处理组细胞增殖cpm值明显低于空白血清组,P<0.05;而且不同浓度含药血清组cpm值比较差异有统计学意义,P<0.05。不同浓度含药血清组中,卵巢上皮性肿瘤细胞的cpm值明显低于生殖细胞肿瘤和性索间质肿瘤细胞的cpm值,P<0.05。结论实验所用复方中药可抑制人卵巢癌新鲜实体瘤细胞的增殖。     

增殖缺陷型腺病毒介导人内皮抑素基因抗乳腺癌的实验

 目的通过建立裸鼠乳腺癌肿瘤模型,在体内实验中进一步证实携带人内皮抑素基因的增殖缺陷型腺病毒Ad-hE的抗肿瘤作用。方法在BALB/c裸鼠皮下种植人乳腺癌细胞MCF-7,建立移植瘤模型。在瘤体内注射Ad-hE治疗,观察肿瘤生长,免疫组化检测肿瘤细胞内皮抑素的表达和计数肿瘤间质中微血管的数量。结果Ad-hE具有明显抑制肿瘤细胞生长的作用,瘤体内注射重组腺病毒后4周,Ad-hE治疗组肿瘤体积为(225.3±90.2)mm3,明显小于Ad-LacZ病毒对照组(794.9±189.8)mm3和空白对照组(890.7±102.5)mm3。免疫组化显示,乳腺癌细胞在感染腺病毒后能够有效表达内皮抑素,阳性细胞比率超过60%以上。Ad-hE治疗组瘤组织中血管数量(16.3±7.3)明显少于空白对照组(54.6±17.6)和Ad-LacZ病毒对照组(49.8±21.2)。结论增殖缺陷型腺病毒介导人内皮抑素的表达,具有明显抑制肿瘤细胞生长的作用。     

卵巢交界性肿瘤细胞增殖活性与其临床病理间的关系

目的:探讨卵巢交界性肿瘤细胞增殖活性与其临床病理间的关系。方法:以WHO(1999年)卵巢肿瘤诊断标准,按照交界性卵巢肿瘤分化程度的不同,为其进行组织学分级,并采用免疫组化法对46例交界性卵巢肿瘤中增殖细胞核抗原(PCNA)的表达进行检测,同时利用流式细胞术(FCM)检测其DNA含量。结果:在交界性卵巢肿瘤中,高分化PCNA标记指数(20.5±12.17)、细胞核DNA含量DI(1.03±0.12)、PI(9.48±6.25)和异倍体率(12.50%)明显低于中低分化的PCNALI(52.35±27.25)、DI(1.20±0.14)、PI(20.34±9.78)和异倍体率(45.45%)(P<0.01),临床I期PCNA标记指数(15.4±11.46)、细胞核DNA含量:DI(1.04±0.11)、PI(12.06±7.68)和异倍体率(14.81%)明显低于Ⅱ、Ⅲ期的PCNALI(46.64±13.48)、DI(1.18±0.12)、PI(23.76±0.89)和异倍体率47.37%(P<0.01),但与其病理类型无明显相关性,(P>0.05)。结论:通过PCNA检测及流式细胞术(FCM)DNA含量分析可较准确地判定肿瘤的增殖潜能,并有可能成为交界性卵巢肿瘤患者预后的重要指标。     

新生血管生成和肿瘤细胞增殖及Laminin表达与鼻腔鳞癌侵袭的关系

目的检测鼻腔鳞状细胞癌(NSCC)组织中CD34、增殖细胞核抗原(PCNA)及基底膜层粘连蛋白(LN)的表达。方法应用SP方法检测26例鼻腔鳞癌组织中CD34、PCNA及LN的表达,并将21例鼻内翻性乳头状瘤(NIP)及14例鼻息肉(NP)做对照,分别检测其微血管密度(MVD),计数PCNA标记指数(PCNALI)和基底膜线性染色完整性。结果CD34在NP、NIP及NSCC中的表达分别为35.17±5.13、52.29±8.96和80.59±12.15,F=79.22,P<0.001;PCNA标记指数分别为29.9±10.2、35.1±6.9和62.8±17.7,F=40.00,P<0.001;LN表达三者之间差异有统计学意义,P<0.01。结论MVD和PCNALI可分别作为独立指标反映NSCC的增殖活性和侵袭发展潜能;基底膜LN的表达可作为NSCC浸润性生长的生物学标志之一。     

PCNA在宫颈鳞癌中的表达及其临床意义

目的　探讨PCNA基因过度表达在子宫颈上皮内瘤变(CIN)及子宫颈鳞形细胞癌中的意义。方法　标本采用常规石蜡切片、HE染色及ABC法免疫组化染色,光镜观察,并对增殖细胞核抗原指数(PCNALI)进行计数。结果　从正常宫颈鳞状上皮到CINⅡ级到子宫颈鳞癌,表达PCNA阳性的细胞范围和阳性强度呈明显增高的趋势,三者间PCNALI差异有显著性(P<001)。在45例鳞状细胞癌中PCNALI随着肿瘤分级增高而增高。鳞癌Ⅰ级、Ⅱ级和Ⅲ级之间PCNALI差异有显著性(P<005)。局部淋巴结有转移癌者和无转移癌者PCNALI差异亦有显著性(P<005)。结论　PCNALI对于检测宫颈鳞癌的发生与发展、早期诊断及判断肿瘤的生物学行为和预测患者的预后等方面具有重要的意义。     

长链非编码RNA-H19促小细胞肺癌细胞株A549 上皮-间质转化及侵袭

背景与目的：近年来研究发现长链非编码RNA(long non-coding RNA,lncRNA)可能在肿瘤的发生、发展中发挥着重要作用,其中H19在膀胱癌、胃癌、肝细胞癌等多种肿瘤中呈现异常过表达,并且能够促进肿瘤增殖,增加肿瘤细胞迁移和侵袭能力等。但H19在非小细胞肺癌中的表达及功能尚不十分清楚。本研究拟观察H19对非小细胞肺癌细胞株A549增殖、上皮-间质转化(epithelial-mesenchymal transition,EMT)及侵袭能力的影响。方法：在A549中通过转染质粒使H19过表达,通过细胞计数试剂盒(cell counting kit-8,CCK-8)检测H19过表达对A549细胞增殖能力的影响,通过Transwell检测其对A549细胞侵袭能力的影响,通过光学显微镜观察细胞的形态学变化,通过蛋白［质］印迹法(Western blot)检测EMT相关蛋白的变化,通过荧光素酶报告基因检测CDH1基因启动子活性的变化。结果：在A549中H19过表达后,细胞增殖能力有所增强(空白对照组D值为1.64±0.02,阴性对照组为1.59±0.04,过表达H19组为1.89±0.02,P<0.05),细胞的侵袭转移能力增强［阴性对照组(30±6)个/视野,过表达H19组(110±7)个/视野,P<0.05)］,细胞发生伪足变长增多、细胞间隙增大等EMT特征的形态学变化,同时蛋白水平CDH1表达降低,而VIM及SNAI2的表达升高,伴有CDH1基因启动子活性下降60%以上(P<0.05)。结论：在非小细胞肺癌细胞株A549中H19过表达可诱使其发生EMT,并促进其增殖及侵袭能力。     

红景天对乳腺癌抑制作用的研究

目的:通过体外和体内实验研究红景天对乳腺癌的增殖抑制作用和浸润转移相关因子表达的影响。方法:采用不同浓度红景天提取物处理乳腺癌MDA-MB-435细胞,制作细胞增殖曲线,观察药物对肿瘤细胞增殖活性的影响;应用流式细胞仪检测红景天提取物对乳腺癌细胞的细胞周期阻滞作用;选择裸鼠乳腺癌MDA-MB-435细胞移植瘤模型,以免疫组织化学染色方法研究红景天提取物对裸鼠移植瘤内MMP-2和组织蛋白酶D(CathD)表达的影响。结果:红景天提取物可显著抑制MDA-MB-435细胞的增殖活性,该抑制作用随着作用时间的延长、药物浓度的增高更为明显。红景天提取物具有阻滞MDA-MB-435细胞增殖周期的作用,主要阻滞于S期,该阻滞作用呈浓度依赖性。在红景天提取物治疗组裸鼠乳腺癌移植瘤中,CathD蛋白表达明显低于生理盐水对照组(免疫组化H-评分均数治疗组为72±50.70,而对照组为168±64.19,P=0.03);治疗组移植瘤MMP-2蛋白表达明显低于生理盐水对照组(免疫组化H-评分均数治疗组为90±29.15,而对照组为176±65.80,P=0.04)。结论:红景天可能通过抑制细胞增殖、浸润能力等多途径对乳腺癌细胞产生一定的抑制作用,其在乳腺癌的防治中具有一定的临床意义。     

非小细胞肺癌VEGF-C表达与淋巴管生成和淋巴转移关系的研究

背景与目的近年来的研究表明,血管内皮生长因子C(VEGFC)通过与其配体(VEGFR3)的结合介导肿瘤淋巴管生成,是形成肿瘤淋巴道转移的最重要因素。淋巴道转移是非小细胞肺癌(NSCLC)常见的主要扩散途径。基于此,本研究用新的淋巴管内皮标志物podoplanin检测NSCLC组织中淋巴管,用淋巴管密度(LVD)表示淋巴管生成情况,探讨NSCLC内VEGFC表达与淋巴管生成和淋巴转移的关系。方法收集66例NSCLC和8例炎性假瘤组织标本,应用免疫组化检测VEGFC、podoplanin的表达,计算VEGFC阳性表达率及淋巴管密度值,分析两者的关系。结果NSCLC组织内VEGFC阳性表达率(75.8%)显著高于肺炎性假瘤(12.5%)(P<0.01),高中分化(76.3%)和低分化(75.0%)之间无显著性差异(P>0.05),淋巴结阳性组中VEGFC阳性率(86.5%)显著高于淋巴结阴性组(62.1%)(P<0.05)。NSCLC组织内LVD(20.4±5.9)显著高于肺炎性假瘤(10.9±4.9)(P<0.01);VEGFC阳性组LVD(21.3±6.0)显著高于VEGFC阴性组(17.7±5.1)(P<0.05),淋巴结阳性组LVD(21.9±5.9)显著高于淋巴结阴性组(18.5±5.5)(P<0.05)。结论淋巴管生成可能是NSCLC淋巴结转移的重要因素,VEGFC参与NSCLC淋巴管生成,从而促进淋巴结转移。     

bFGF单抗协同替吉奥抑制肺癌Lewis细胞的增殖及移植瘤血管新生

目的:探讨碱性成纤维生长因子(basic fibroblast growth factor,bFGF)单抗与替吉奥(gimeracil and oteracil porassi-um,又称S-1)联合应用体内外抑制小鼠Lewis肺癌细胞增殖、移植瘤生长及转移、肿瘤血管新生的协同作用。方法:CCK-8法检测bFGF单抗及S-1对Lewis细胞增殖的抑制作用。建立C57BL/6小鼠Lewis肺癌自发转移瘤模型,32只小鼠随机分成生理盐水(NS)组、bFGF单抗组、S-1组和bFGF单抗+S-1组,每组8只;测量瘤体,绘制生长曲线,称瘤质量并计算抑瘤率;计数各组肺表面转移瘤结节;CD31标记血管内皮细胞,计数转移瘤微血管密度(microvessel density,MVD)。结果:bFGF单抗、S-1剂量依赖性抑制Lewis细胞增殖(P<0.05),联合用药组抑制率明显高于单药组(P<0.05或P<0.01)。bFGF单抗组、S-1组以及bFGF单抗+S-1组对Lewis转移瘤的抑瘤率分别为37.8%、47.7%、65.9%,联合组抑瘤率明显高于单药组(P<0.05或P<0.01)。联合组肺表面转移结节、微血管密度明显低于单药组(2.71±0.76vs6.57±0.98、4.71±0.76;21.6±2.9vs33.4±4.9、41.9±6.3;P<0.05或P<0.01)。结论:bFGF单抗联合S-1对Lewis肺癌移植瘤具有协同抑制作用,其机制与抑制细胞增殖及血管新生有关。     

肺鳞癌引流区域淋巴结细胞对自体肿瘤凋亡相关蛋白表达水平的影响

目的:研究肺癌引流淋巴结(tum or draining lymph nodes,TDLN)细胞对自体肿瘤的凋亡相关蛋白表达水平的影响。方法:手术时取肺癌患者肿瘤引流淋巴结2~4枚,制备细胞悬液,分别用IL-2(I-TDLN)、IL-2+GM-CSF+IL-4(G-TDLN)刺激后,对建立人肺癌细胞移植瘤模型的裸鼠进行免疫干预,检测不同组裸鼠移植瘤细胞的凋亡率和Bcl-2、Bax、survivin、Fas、FasL蛋白的表达。结果:对照组荷瘤裸鼠癌组织的凋亡率为(6.07±3.31)%,IL-2处理组的凋亡率为(12.11±1.19)%;LAK细胞组的凋亡率为(21.42±1.82)%,I-TDLN细胞组的凋亡率为(24.60±0.96)%,G-TDLN细胞组的凋亡率为(32.76±4.46)%。方差分析显示各组间肿瘤组织的凋亡差异显著(P<0.001)。Fas及FasL蛋白在空白对照组及IL-2、LAK、I-TDLN、G-TDLN干预组移植瘤细胞表达的FI值均无统计学差异(P=0.246,P=0.528)。然而经LAK、I-TDLN、G-TDLN干预后,移植瘤细胞Bax蛋白的表达FI值明显高于空白对照组及IL-2作用组(P<0.001);而Bcl-2蛋白在IL-2、LAK、I-TDLN和G-TDLN干预组小鼠移植瘤细胞中的表达FI值明显低于空白对照组(P<0.001);同样survivin蛋白在LAK、I-TDLN和G-TDLN干预组移植瘤细胞中的表达FI值明显低于空白对照组及IL-2作用组(P<0.001)。结论:肺癌引流淋巴结细胞对自体肿瘤的杀伤可能与凋亡蛋白有关。     

周围型肺癌CT征象与PCNA蛋白表达之间关系的研究

目的 :研究周围型肺癌PCNA蛋白表达与CT表现之间的关系。方法 :应用链菌素亲生物素—过氧化物酶法(SP法 )检测 5 3例经病理证实的周围型肺癌组织中PCNA蛋白的表达 ,并分析其与CT征象间的关系。结果 :PCNA蛋白表达与肿瘤分化程度、恶性度、大小、深分叶征、淋巴结转移、空洞征和胸膜凹陷征有关 ,与毛刺征无关。结论 :肺癌组织分化越低其PCNA表达越高 ,CT征象中肿瘤≥ 3cm、深分叶征、淋巴结转移、空洞征和胸膜凹陷征与PCNA蛋白表达有密切关系     

周围型肺癌CT征象与p53蛋白及增殖细胞核抗原表达间关系的研究

目的研究周围型肺癌ＣＴ征象与ｐ５３蛋白及增殖细胞核抗原（ＰＣＮＡ）表达间的关系。方法运用ＳＰ免疫组化法,检测３２例经病理证实的周围型肺癌组织中ｐ５３蛋白及ＰＣＮＡ的表达,并回顾性分析其与术前ＣＴ征象间的关系。结果ｐ５３蛋白、ＰＣＮＡ表达与瘤体大小、深分叶征、空洞、胸膜凹陷征、纵隔淋巴结转移有关,与毛刺征无关。结论周围型肺癌ＣＴ征象中,瘤体直径＞３ｃｍ,或出现深分叶征、空洞、胸膜凹陷征、纵隔淋巴结转移者,具有相对更高的恶性程度,肿瘤细胞的增殖更为活跃。     

Proliferative activity of gastric cancer assessed by immunostaining for proliferating

The growth activity of 107 gastric carcinomas was assessed by immunohis-tochemical staining for formalin-fixed, paraffin-embedded tissue with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). When the tumor doubling times (Tds) of 10 patients were estimated from the serum levels of carcinoembryonic antigen and carbohydrate antigen 19–9, there was an inverse correlation between the Tds and PCNA labeling index (LI) at P = 0.055. Flow-cytometric analysis was carried out by double staining for PCNA and DNA using fresh materials from 14 patients. The PCNA-positive cell fraction revealed by flow cytometry showed a good linear correlation with PCNA LI in routinely stained tissue. The LI of well-differentiated adenocarcinoma was significantly higher than that of the poorly differentiated type. When the LI was analyzed in well- or poorly differentiated adenocarcinoma, the value was significantly higher in the well-differentiated type with hepatic metastasis and in the poorly differentiated type with lymph node metastasis. © 1993 Wiley-Liss, Inc.     

Relationship between immunohistochemical evaluation of thymidylate synthase and proliferating cell nuclear antigen labeling index in gastrointestinal carcinoma

We undertook this study to clarify the effect of immunohistochemical expression of thymidylate synthase (TS) on proliferative activity of carcinoma lesions in patients with gastrointestinal carcinoma. TS was immunohistochemically evaluated in 53 gastric carcinoma and 51 colorectal carcinoma patients using anti-TS polyclonal antibody. Proliferative activity represented by proliferating cell nuclear antigen (PCNA) labeling index (LI) was also immunohistochemically estimated using monoclonal antibody PC10. Then, the correlation between TS expression and PCNA LI was investigated. Both in gastric and colorectal carcinoma, the PCNA LIs of the high-TS group were significantly higher than those of the low-TS group. In gastric carcinoma, the PCNA LIs of the high-TS group were higher than those of the low-TS group in differentiated adenocarcinoma, in the depth of mucosal and/or submucosal layer, in cases without lymph node metastasis, and notwithstanding lymphatic or venous invasion. In colorectal carcinoma, PCNA LIs of the high-TS group were higher than those of the low-TS group in well differentiated adenocarcinoma, in the depth of serosa, in cases with lymph node metastasis, in cases with lymphatic invasion, and notwithstanding venous invasion. Immunohistochemical expression of TS was correlated with the proliferative activity represented by PCNA LI, but was not identical with PCNA LI.     

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.     

Expression of thymidylate synthase is correlated with proliferative activity in non-small cell lung cancer (NSCLC)

Many experimental studies have revealed that enhanced thymidylate synthase (TS) expression is significantly correlated with higher proliferative activity of tumor cells, which may account for a poor prognosis of high-TS patients. However, only a few clinical studies have focused on the correlation between TS status and cell proliferation. Therefore, we assessed the correlation between TS expression and proliferative index (PI) as a marker of cell proliferation or p53 status in a total of 109 patients with completely resected pathologic stage I, non-small cell lung cancer (NSCLC). PI was defined as the percentage of tumor cells with positive staining against proliferative cell nuclear antigen (PCNA). The mean PIs of TS-high and TS-low tumors were 48.2% and 34.4% respectively, showing a significantly higher proliferative activity of TS-high tumor (P=0.020); when stratified according to histological type, the difference was significant in adenocarcinoma (P=0.038), but not in squamous cell carcinoma. There was no significant correlation between TS expression and p53 status. In conclusion, tumor cells with higher TS expression have higher proliferative activity in NSCLC, especially in adenocarcinoma.     

错配修复基因hMLH1、hMSH2及PCNA在肺癌组织中的表达及意义

 目的　探讨人类错配修复基因hMLH1、hMSH2及增殖细胞核抗原PCNA在肺癌组织中的表达及意义。方法　运用免疫组织化学S P法对 5 6例肺癌组织中hMLH1、hMSH2及PCNA的表达进行检测。结果　 5 6例肺癌组织中hMLH1的阳性表达率为 35 % ,hMSH2阳性表达率为 2 8.6 % ,分化程度高者阳性率显著高于分化程度低者 (P <0 .0 1) ,有淋巴结转移者hMLH1及hMSH2阳性率低于无淋巴结转移者 (P <0 .0 5 ) ,不同病理组织学类型之间hMLH1及hMSH2表达无显著差别 (P >0 .0 5 ) ;5 6例肺癌组织中分化程度低者PCNA标记指数高于分化程度高者 (P <0 .0 1) ,有淋巴结转移者PCNA标记指数高于无淋巴结转移者 (P <0 .0 5 ) ,hMLH1及hMSH2阴性表达者的PCNA标记指数明显高于hMLH1及hMSH2阳性表达者 (P <0 .0 1) ,不同病理组织学类型之间PCNA标记指数无显著差别 (P >0 .0 5 )。结论　hMLH1及hMSH2基因的缺陷及PCNA的表达与肺癌的发生发展过程并与分化程度及有否淋巴结转移有关     

Prognostic-significance of proliferating cell nuclear antigen (pcna) in adenocarcinoma of the lung

The aim of the study was to investigate the prognostic value of the proliferating cell nuclear antigen (PCNA) expression in non-small cell lung carcinomas (NSCLC). Two hundred and sixteen patients with previously untreated NSCLC entered into this investigation. For assessment of PCNA expression the streptavidin-biotinylated peroxidase complex method was performed using imnuunohistochemistry and Mab PC10. The tumors were scored for the percentage of PCNA-positive cells (low proliferative activity less than or equal to 25%; high proliferative activity >25%). Univariate analyses of all patients showed a trend that those with high proliferating tumors had shorter survival times than those with lower proliferating tumors. Similar results were obtained when the analysis was restricted to squamous cell carcinomas. Patients with adenocarcinomas and with high proliferating tumors had significantly shorter survival times than those with low proliferating tumors (p=0.028). No correlation was found between extent of tumors or metastasis and expression of PCNA. The multivariate analysis including age, sex, extent of tumors and metastasis as well as PCNA revealed a highly significant influence of extent of tumors (p=0.007) and metastasis (p=0.003) whereas all other factors including PCNA were of no significant influence.     

Cell proliferation in childhood acute leukemia. Comparison of Ki-67 and proliferating cell nuclear antigen immunocytochemical and DNA flow cytometric analysis.

The proliferative activity of bone marrow leukemia cells was determined by DNA flow cytometric (FCM) analysis and labeling index (LI) of Ki-67 monoclonal antibodies and proliferating cell nuclear antigen (PCNA) autoantibodies in 73 children with acute leukemia. LI of Ki-67 varied greatly from patient to patient (range, 0.4% to 42.2%; mean, 18.8%) and differed significantly between acute lymphoblastic leukemia (ALL) and acute nonlymphoblastic leukemia (ANLL). In ALL, the Ki-67 LI showed a positive correlation with the S-phase fraction (SPF) determined by DNA FCM analysis, whereas, in ANLL, there was a discrepancy between the Ki-67 LI and SPF. In contrast, LI of PCNA varied less among the patients (range, 57.2% to 100%; mean, 90.3%), and the value was always higher than that of the Ki-67 LI in individual patients. A significant relationship between PCNA LI and the percentage of blast cells was found in peripheral blood leukocytes from patients with leukemia. These results suggest that the Ki-67 LI reflects differences in the proliferative activity depending on the subtype of the disease and that the PCNA LI is useful as a marker of proliferating cells.     

Proliferating Cell Nuclear Antigen Immunostaining in Breast Cancer and Its Relation to Prognosis

Proliferating cell nuclear antigen (PCNA) appears in the cellnuclei during the late G1 to S phases of the cell cycle andis thought to be closely related to cellular proliferation.The authors have conducted an immunohistochemical study in orderto investigate the tissue expression of PCNA and its clinicalsignificance in breast cancer. Excluding cases with absolutelyno positive cells on the section specimen, the mean value (%)for the PCNA labeling index (LI) was 30.4 in 187 cases of invasiveductal carcinoma. No correlations between PCNA LI and any clinicopathologicalfactors such as tumor diameter and tumor stage were observed.Also, no significant correlation was observed with Ki-67 LI.A positive correlation was, however, observed with the tissueexpression of c-erbB-2 protein. We divided 82 patients withstage II invasive ductal carcinoma into PCNA LI of <10, PCNALI of 10–50 and PCNA of >50, and analyzed the specimensfor any correlation with prognosis. The group with PCNA LI of>50 had significantly poorer prognoses than the other groups.From the above, we concluded immunostaining for PCNA to be usefulas a prognostic factor and as an indicator of the degree ofmalignancy in breast cancer.