慢性糜烂性胃炎与胃癌的免疫组织化学比较研究——P~(21ras)、 P~(53)、PCNA和CEA表达的观察

本研究对31例慢性糜烂性胃炎粘膜活检组织及14例手术切除的胃癌组织的P21ras、P53蛋白、细胞核增殖抗原（PCNA）、癌胚抗原（CEA）的表达采用LSAB免疫组织化学标记。结果发现P21ras在慢性糜烂性胃炎粘膜上皮和胃癌肿瘤细胞中表达阳性率分别为67.7％和65.0％（P>0.05）;P53表达阳性率分别为0和21.4％（0.010.05）;CEA表达阳性率分别为29.0％和78.6％（P<0.01）。慢性糜烂性胃炎较高的P21ras表达和较高的细胞增生活性（PCNA表达）,提示其有一定的转化趋势。慢性糜烂性胃炎粘膜上皮的CEA表达可能提示其为今后发展成肠型胃癌的前驱病变。     

胃癌发生中增殖细胞核抗原与bcl-2和p53蛋白表达的意义

目的:了解细胞增殖及基因bcl-2、p53的表达在浅表性胃炎→萎缩性胃炎→肠上皮化生→不典型增生→早期胃癌→进展期胃癌这一演化过程中的意义。方法:采用免疫组化法检测增殖细胞核抗原(PCNA)标记和bcl-2、p53蛋白表达。结果:浅表性胃炎、萎缩性胃炎、肠上皮化生、不典型增生、早期胃癌和晚期胃癌的PCNA指数分别为11.3 % ±2.2% 、18.9% ±6.5% 、20.33% ±7.3% 、40. 03% ±10.6% 、53.08% ±10.9% 和72.44% ±38.4% ;bcl-2表达分别为10.0% 、23.3% 、40.0%、56.7% 、85.7% 和46.7%;p53蛋白表达分别为0% 、0% 、0% 、4.3%、14.3% 和53.3% 。各期病变中的这三项指标绝大多数均有显著差异(P<0.05～0.01)。结论:(1)在胃癌演化过程中,PCNA呈持续上升趋势。(2)在胃癌中,bcl-2蛋白的表达与p53蛋白的表达呈反向关系,前者可能是胃癌早期的行为,后者则可能是胄癌中晚期的行为。     

PCNA、P53与胎儿食管上皮细胞增殖特性的关系

目的 初步探讨增殖细胞核抗原(proliferation cell nuclear antigen,PCNA)和抑癌基因p53与胎儿食管上皮细胞增殖特性的关系。方法 采用免疫组化ABC法检测胎儿食管组织中PCNA和p53的表达状况。结果PCNA在31例胎儿标本中全部呈阳性反应,PCNA单位面积平均阳性细胞数为506±239/mm~2,与成人不同类型食管上皮组织单位面积PCNA免疫阳性细胞数相比,差异具有显著性,P<0.05。p53免疫组化染色阳性细胞核呈棕黄色,胞浆未见阳性反应,其阳性率为10％(3/31)。结论 PCNA和p53在胎儿食管上皮组织中的表达可反映胎儿食管上皮旺盛的增殖特性。     

p53与一氧化氮的关系及其在肝癌发生中的作用

目的：研究p53与一氧化氮（NO）的关系及其在肝癌发生中的作用。方法：用免疫组化法对21全肝癌标本中p53、诱导型一氧化氮合酶（iNOS)及增殖细胞核抗原（PCNA）的表达进行原位检测和观察。结果：癌旁组织（距癌组织边缘＜1．5cm)iNOS表达多呈阳性,非癌组织（距离组织边缘＞1．5cm)多呈阴性或弥漫弱阳性;iNOS在周边癌组织及侵入纤维组织的癌细胞中呈阳性,癌组织核心多呈阴性或弥漫弱阳性。p53阳性率为47．6％。p53表达阳性区,iNOS表达也呈阳性。PCNA的表达与p53及iNOS一致。结论：肝癌旁组织中p53的表达与NO相关,与肝癌的发生、发展有关。     

膀胱癌组织中Bcl-2、PCNA、p53的表达变化及意义

目的观察膀胱癌组织中Bcl-2、PCNA、p53的表达变化，并探讨其临床意义。方法用流式细胞术检测3l例膀胱癌组织中的Bcl-2、PCNA、p53，并与18例正常膀胱黏膜组织作对照。PI染色法和TUNEL法分别检测上述标本的细胞周期及凋亡细胞。结果31例膀胱癌组织中，Bcl-2阳性表达率为58．1％，p53为67．7％，PCNA中强度阳性。正常膀胱黏膜组织Bcl-2阳性表达率为16．7％、p53不表达、PCNA弱阳性，两者相比，P均〈0．01。Bcl-2、PCNA、p53的表达与膀胱癌的临床分级或分期相关。膀胱癌细胞周期分布异常，19例出现DNA异倍体，s期细胞增加，但未发现明显的周期阻滞现象。膀胱癌细胞凋亡增加。结论膀胱癌组织中Bcl-2、PCNA、p53过度表达，可出现DNA异倍体，均提示预后不良。     

胃癌及癌前病变中p53蛋白的检测及意义

探讨p53蛋白表达与胃癌及癌病变的相互关系,方法：用免疫组化染色示检测33例肠化,26例异型增生和26例胃癌组织中p53蛋白的表达。结果：p53蛋白在胃癌组织中表达率最高（61．5％）,在异型增生和肠化组织中的表达率分别为34．6％和12．1％,组间有显著差异,各期胃癌组织中p53蛋白的表达无显著差异,结论：p53蛋白在胃癌前病变中已有阳性表达,在肠化、异型增生及胃癌组织中,其表达率依次增高,p53蛋白积累主要发生在癌前病变晚期及胃癌早期,其表达与胃癌发生密切相关。     

ToPoⅡ、PCNA在慢性萎缩性胃炎患者胃黏膜中的表达及意义

目的观察慢性萎缩性胃炎（CAG）患者胃黏膜标本中DNA拓扑异构酶Ⅱ（ToPoⅡ）和增殖细胞核抗原（PCNA）的表达及意义。方法采用免疫组化S-P法对106例CAG进行TopoⅡ和PCNA染色,同时进行幽门螺杆菌（HP）检测。结果TopoⅡ阳性表达与胃黏膜HP感染、异型增生间有关,而与胃黏膜萎缩和化生程度无明显相关;PCNA阳性表达随胃黏膜萎缩、化生、异型增生和HP感染程度加重而增强,但除轻度异型增生与无增生者有显著性差异外,其余均无显著性差异。结论不同增生CAG中TopoⅡ和HP检测较PCNA有意义,利于CAG异型增生监测和预防肿瘤的发生。     

胃黏膜癌前病变中p53和增殖细胞核抗原的表达及其临床意义

目的探讨胃黏膜癌前病变中p53和增殖细胞核抗原（PCNA）的表达及其临床意义。方法顺序选择病理检查为肠上皮化生、不典型增生、肠上皮化生不典型增生共存的患者各20例（分别为A、B和C组）,另选20例正常者作为对照（D组）。免疫组化法检测其组织中p53和PCNA的表达。结果胃黏膜癌前病变中p53蛋白、PCNA表达水平均高于正常黏膜（P〈0．01）,表达水平从肠上皮化生、不典型增生到二者共存者呈递增趋势。结论p53和PCNA表达对评估胃黏膜癌前病变发展趋势有重要的临床价值,有助于早期发现胃癌。     

NACT前后宫颈癌组织中PCNA、p53、P—gp的表达变化及意义

目的探讨宫颈癌新辅助化疗（NACT）前后增殖细胞核抗原（PCNA）、抑癌基因p53和P-糖蛋白（P-gp）在宫颈癌组织中的表达变化及其与化疗疗效的关系。方法对60例局部晚期宫颈癌患者行NACT,采用免疫组化法检测化疗前后宫颈癌组织中的PCNA、p53、P-gp。结果化疗前宫颈鳞癌组织中PCNA、p53和P—gp阳性表达率分别为86．7％、60．0％、56．7％;化疗后分别为93．3％、83．3％、83．3％,化疗前后p53、P—gp阳性率相比,P均〈0．05。NACT前宫颈癌组织p53、P-gp表达阴性者NACT有效率与p53、P—gp表达阳性者相比,P均〈0．05。结论NACT前后宫颈癌组织中p53、P-gp的表达水平有显著差异,p53、P-gp的表达水平可作为宫颈癌化疗疗效敏感性的预测指标．     

原发性肝细胞癌EGFR,PCNA表达及相互关系的研究

收集原发性肝细胞癌60例,肝异型增生12例及正常肝细胞10例,进行增殖细胞核抗原(Proliferating Cell Nuclear Antigen、PCNA)和表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)免疫组化观察,探讨它们在肝细胞癌中的表达情况,分析不同分化程度肝癌之间表达的差异及两者之间的关系。结果表明:在正常肝组织阳性率很低,随着细胞增长,特别是异型增生,阳性率逐渐增高。在癌Ⅰ级达到高峰,而在癌组织随着癌分化程度降低,阳性表达率逐渐下降。而且还表明EGFR的表达与PCNA表达基本一致,呈正相关关系。这说明在细胞增殖活动中,这两者的作用都很重要,都能从不同方面反映细胞的增殖活性。     

Flow cytometric analysis and immunohistochemical staining for the p53 protein and proliferating cell nuclear antigen in submucosal carcinoma of the esophagus

BACKGROUND/AIMS: The aim of this study was to examine the role of p53 gene and tumor proliferating activity using anti-proliferating cell nuclear antigen (PCNA) in squamous cell carcinoma (SCC) of the esophagus with invasion restricted to the submucosa. Their DNA contents and microscopic histopathological aspects were also studied. METHODOLOGY: Thirty-four submucosal SCC were studied histopathologically including immunohistochemical and flow cytometric analysis. RESULTS: DNA diploid was observed in 15 (44.1%) and DNA aneuploid in 19 (55.9%) cases. DNA ploidy patterns were relatively closely correlated with survival. Staining for the p53 product was positive in 61.8% of all cases. The average PCNA labeling rate (LR) was 55.9 +/- 16.7%. The incidence of lymph node metastasis was relatively higher in DNA aneuploid and high PCNA LR (> or = 50%) groups. There was, however, no significant correlation between p53 protein expression and lymph node metastasis. CONCLUSIONS: Our study suggests that DNA aneuploid and high PCNA LR are unfavorable characteristics and that p53 expression may not have a prognostic value.     

原位杂交方法检测胃癌及其癌前病变中抑癌基因p53的表达

目的用原位杂交方法检测胃粘膜癌前病变及胃癌组织中ｐ５３ｍＲＮＡ的表达,并观察感染Ｈｐ对其表达的影响．方法病理证实为慢性胃炎６６例和胃癌１６例,用地高辛标记的ｃＤＮＡ为探针进行原位杂交实验,检测其胃粘膜组织中ｐ５３ｍＲＮＡ表达,用单克隆抗体ＤＯ０１进行免疫组化检测Ｐ５３蛋白的表达．结果在慢性萎缩性胃炎、肠化生、异型增生及胃癌中,原位杂交方法检测ｐ５３ｍＲＮＡ表达率分别为５３９％,５２３％,４２８％和２５％,免疫组化方法检测Ｐ５３蛋白的表达率分别为００％,５３％,１５４％和２５％．ｐ５３ｍＲＮＡ的表达与蛋白的表达无明显的一致性,ｐ５３ｍＲＮＡ的表达可以在Ｐ５３蛋白阴性及阳性的细胞中．在２６例萎缩性胃炎中,１４例检测到ｐ５３ｍＲＮＡ的表达,而其中１６例（包括１４例阳性病例）无一例检测到Ｐ５３蛋白的表达．在肠化生、异型增生及胃癌组织中也发现有类似的情况．Ｈｐ感染组与未感染组,ｐ５３ｍＲＮＡ表达率之间统计学检验Ｐ＜００５．结论在胃癌及其癌前病变中,随着病变的发展,ｐ５３ｍＲＮＡ的表达率随之下降,Ｈｐ对其表达有明显的影响     

胃粘膜癌变过程中幽门螺杆菌感染与p53,c-erbB-2基因表达的研究

目的探讨胃粘膜癌变过程中幽门螺杆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ,Ｈｐ）感染与ｐ５３,ｃｅｒｂＢ２基因表达的关系．方法浅表性胃炎１６例,肠上皮化生２２例,异型增生１４例,早期胃癌１８例及进展期胃癌４０例作为研究对象．用ＷａｒｔｈｉｎＳｔａｒｙ银染色法检测Ｈｐ,用免疫组化Ｓｐ法检测ｐ５３和ｃｅｒｂＢ２的基因表达产物．结果Ｈｐ,ｐ５３,ｃｅｒｂＢ２在浅表性胃炎的检出率各为５００％,００％,００％;在肠上皮化生的检出率各为５９１％,２２７％,１３６％;在异型增生的检出率各为８５７％,６４３％,２８６％;在早期胃癌的检出率各为１６７％,３３３％,１１１％;在进展期胃癌的检出率各为５０％,５２５％,５５０％;在癌旁粘膜的Ｈｐ检出率为８６７％;在癌前病变中,Ｈｐ阳性组的ｐ５３,ｃｅｒｂＢ２表达率均高于Ｈｐ阴性组．结论Ｈｐ感染参与了胃癌前病变的发生与发展;Ｈｐ感染可引起野生型ｐ５３基因失活和ｃｅｒｂＢ２基因激活,从而导致胃粘膜的癌变．     

Alterations of p53 and PCNA in cancer and adjacent tissues from concurrent carcinomas of the esophagus and gastric cardia in the same patient in Linzhou,a high incidence area for esophageal cancer in northern China

AIM:To characterize the alteration and significance of p53 and PCNA in cancer and adjacent tissues of concurrent cancers from the esophagus and gastric cardia in the same patient.METHODS: P53 and PCNA protein accumulation in 25 patients with concurrent cancers from the esophagus and gastric cardia (CC, concurrent carcinomas of esophagealsquamous cell carcinoma and gastric cardia adenocarcinoma)were detected by immunohistochemical method (ABC).RESULTS: In CC patients, both esophageal squamous cell carcinoma (SCC) and gastric cardia adenocarcinoma (GCA)tissues showed different positive immunostaining extent ofp53 and PCNA protein (P&gt;0.05). The positive immunostainingrates for p53 and PCNA were 60 % (15/25) and 92 % (23/25), respectively in SCC; and 40 % (10/25) and 88 % (22/25), respectively in GCA. “Diffuse“ immunostaining patternwas frequently observed in both p53 and PCNA. High coincidence rates for p53 and PCNA positive staining were observed in SCC and GCA from the same patients, andaccounted for 56 % and 96 %. In SCC patients, with thelesions progressed from normal esophageal epithelium (NOR)to basal cell hyperplasia (BCH) to dysplasia (DYS) tocarcinoma in situ (CIS) to SCC. the oositive rates for p53were 27 %, 50 %, 50 %, 29 % and 72 %, and 55 %, 70 %,75 %, 71% and 93 % for PCNA, respectively. In GCA, with the lesions progressed from normal gastric cardia epithelium to DYS to CIS to GCA, the positive rates of p53 expression were 44 %, 27 %, 22 % and 36 % respectively, the difference was not significant; the positive rates of PCNA protein expression were 67 %, 64 %, 67 % and 86 %, respectively.The χ^2 test, Fisher‘s Exact Test, Mantel-Haenszel χ^2 Test and Kappa Test were used for the statistics.CONCLUSION: The high coincident alterations for P53 and PCNA in SCC and GCA from the same patient indicate the possibility of similar molecular basis, which provides important molecular basis and etiological clue for similar geographic distribution and risk factors in SCC and GCA.Chen H, Wang LD, Guo M, Gao Alterations of p53 and PCNA inSG, Guo HQ, Fan ZM, Li JL.cancer and adjacent tissuesfrom concurrent carcinomas of the esophagus and gastric cardiain the same patient in Linzhou, a high incidence area foresophaqeal cancer in northern China. World J Gastroenterol     

Immunohistochemical Study of Colorectal Polyps with Antibodies against CEA,CA19-9, CA125, CA15-3 (DF3), PCNA and p53

Abstract: We analyzed the expression of CEA, CA19-9, CA125, CA15-3 (DF3), PCNA and p53 immunohistochemically in 14 tissue specimens of mucosal cancers in adenoma, seven tubulovillous adenoma specimens, and 16 tubular adenoma specimens. The rates of positive staining for mucosal cancer in adenoma, tubulovillous adenoma and tubular adenoma specimens, respectively, were: for CEA: 100%, 85.7% and 75%; for CA19-9: 71.4%, 71.4% and 56.2%; for CA125:0%, 0% and 0%;for CA15-3 (DF3): 64.3 %, 0% and 0 %; for PCNA: 100%, 88.9% and 56.2%; and for p53: 35.7%, 0% and 0% . The results suggest that the expressions of CEA, CA19-9, CA15-3 (DF3), PCNA and p53 are related to colorectal tumorigenesis. None of the specimens studied showed staining for CA125, suggesting that CA125 is not involved in the early stages of colorectal carcinogenesis. There was no significant difference in the rates of positive staining for CEA and CA19-9 among mucosal cancer in adenoma, tubular adenoma and tubulovillous adenoma specimens. However, the rates of positive staining for PCNA and p53 were significantly higher in mucosal cancer in adenoma specimens than for tubular adenoma specimens (p<0.05), and the rate of CA15-3 (DF3) positive staining was significantly higher for mucosal cancer in adenoma than for tubulovillous adenoma (p<0.01) and tubular adenoma (p< 0.001) specimens. Therefore, the CA15-3 (DF3) antigen is an immunohistochemical marker for colorectal carcinomas. The present results suggest that CA15-3 (DF3), PCNA and p53 play important roles in the genesis of colorectal adenomas.     

p21和增殖细胞核抗原在肝硬化组织的表达及其与肝细胞不典型增生的关系

目的探讨p21和增殖细胞核抗原（proliferatingcellnuclearantigen,PCNA）的相互关系及它们在肝硬化、肝细胞不典型增生（LCD）、肝细胞癌(HCC)形成中的作用。方法运用S-P法对60例单纯肝硬化、30例癌旁肝硬化及27例HCC的p21、PCNA及HBsAg表达情况进行实验研究。结果癌旁肝硬化、单纯肝硬化、癌组织p21阳性率分别为90%、68.33%、62.96%。癌旁肝硬化与单纯肝硬化及癌组织之间,差别有显著性意义(P＜0.05)。伴LCD改变的肝硬化,p21、PCNA及HBsAg阳性率分别为92.45%、73.59%、64.92%均高于不伴LCD改变的肝硬化组织（P＜0.05）。HBsAg阳性及PCNA表达阳性的肝硬化组织,其p21阳性表达率分别为87.32%、86.21%,均明显高于HBsAg阴性及PCNA阴性的肝硬化组织（P＜0.01）。结论(1)p21的过度表达可能与HCC的起始过程有关,在HCC形成发展的早期阶段发挥重要作用。(2)LCD是一群具有肿瘤性增殖潜能的癌前细胞群,尤其是伴有HBV感染,且有p21及PCNA共同过量表达者,有发生HCC的高度危险。(3)HBV感染及PCNA过量表达与p21表达密切相关。     

Flow cytometric DNA analysis, and immunohistochemical p53, PCNA and histopathologic study in primary achalasia: preliminary results

BACKGROUND/AIMS: Primary achalasia is a premalignant disorder of the esophagus. The studies for esophageal cancer pathogenesis may reveal early diagnosis of esophageal cancer. DNA aneuploidy, p53 mutations and cellular proliferation are important factors in cancer development. As far as we know, we have not encountered any study on these factors in achalasia. METHODOLOGY: We studied DNA ploidy by flow cytometry and p53 and PCNA index by immunohistochemical technique and studied histopathology in the esophageal mucosa of primary achalasia and control patients. RESULTS: DNA analysis revealed aneuploidy in 2 of 20 achalasia patients but none of the 18 control patients. Sixty-five percent of achalasia and 22% of normal patients showed p53 positivity (P < 0.05). We have found normal mucosa, basal cell hyperplasia-esophagitis and dysplasia in 13, 22 and 3 patients and p53 positivity in 2, 12 and 3 of these patients, respectively (P < 0.05). PCNA labeling indexes (as % +/- SD) were 34.8 +/- 12.2, and 28.4 +/- 9.3 in achalasia and control groups, respectively (P > 0.05). PCNA labeling index was 28.0 +/- 8.2 in p53(-) and 36.0 +/- 12.9 in p53(+) patients (P < 0.05). PCNA indexes were found 29.3 +/- 9.6 in normal histopathologic group, 31.8 +/- 13.4 in basal cell hyperplasia-esophagitis, and 41.7 +/- 6.5 in dysplasia group (P > 0.05). CONCLUSIONS: DNA aneuploidy, p53 positivity, and higher cellular proliferation index may have important role in the pathogenesis of esophageal cancer in primary achalasia.     

MAbCOL—1在老年胃癌及癌前病变病人粪便,胃液中表达的研究

采用酶免疫电泳印迹法检测了１６６例老年人的粪便及２１５例老年人的胃液，结果显示：ＭＡｂＣＯＬ－１所对应的抗原癌胚抗原（ＣＥＡ）在老年人各组粪便、胃液中的阳性率分别为：胃癌７０％、７３％，萎缩性胃炎６３％、６７％，不典型增生６７％、７１％，浅表性胃炎及正常对照组全部为阴性。从而提示：ＭＡｂＣＯＬ－１不但在胃癌中有较高表达，而且早在癌前病变中就已有表达，而非癌前病变组及正常人全部为阴性，说明ＣＥＡ的表达与胃癌的发生、发展密切相关，可作为早期胃癌诊断的参考指标，用于胃癌高危人群的普查。