Bcl-2与PCNA在大肠腺瘤和大肠癌中的表达

目的　探讨增殖细胞核抗原 (proliferatingcellnuclearantigen ,PCNA)与原癌基因bcl 2在大肠腺瘤和大肠癌中的表达变化以及与大肠腺瘤和大肠癌的发生、发展的关系。方法　采用免疫组化S P法 ,分别检测PCNA与bcl 2在 18例大肠腺瘤和 18例大肠癌中的表达。结果　PCNA在大肠腺瘤和大肠癌中的标记指数分别为 65 95± 12 94%和 84 5 3± 10 3 9% ,两者均明显高于正常肠粘膜中的指数 ,P <0 0 0 1,两者相比有显著性差异 ,P <0 0 1。Bcl 2在大肠腺瘤和大肠癌中的表达分别为 81 10± 10 0 0 %和 65 78±12 95 % ,两者均明显高于正常肠粘膜中的表达P <0 0 0 1。两者相比有显著性差异 ,P <0 0 1。结论　大肠癌的癌前病变腺瘤中存在活跃的细胞增殖 ,而且同时有细胞凋亡的改变 ,细胞增殖和细胞凋亡的调控失常共同导致了肿瘤的发生。     

Apoptosis,PCNA and p53 in hepatocellular carcinoma

BACKGROUND/AIMS: The regulation of cell number is present in normal tissues but is lost in malignant neoplasms. The real meaning of these alterations is not well known. Apoptosis is the programmed cell death. p53, a tumor suppressor gene, has an important function in DNA repair and in regulation of apoptosis. Mutations of p53 were described in malignant tumors and can be the cause of the alterations of this balance. Proliferating cell nuclear antigen is an auxiliary protein present during G1-late phase and S phase. The aim of this study was to compare cell proliferation, apoptosis and expression of p53 in hepatocellular carcinoma. METHODOLOGY: Fifteen patients with hepatocellular carcinoma were included. Ten patients were men. The mean age of the patients was 55.53 years old. Cirrhosis was positive in nine patients, 5 were HBsAg positive and none were anti-HCV positive. The mean level of AST and ALT were respectively, 62.79 and 50.64. Formalin-fixed and paraffin-embedded tissues from these patients were examined retrospectively. Apoptosis were measured by counting the number of apoptotic bodies in 500 tumoral cells. The expression of p53 oncogene and the PCNA were determined by immunohistochemical method, using avidin-biotin method (DAKO). The p53 were considered positive when the number of positive nuclei was more than 5% of the tumoral cells. The proliferative activity was determined by proliferating cell nuclear antigen labeling index. RESULTS: The proliferating cell nuclear antigen-labeling index ranged from 0.48 and 0.95 (mean: 0.82). The p53 was positive in five patients. The number of apoptotic bodies counted ranged from 0 to 15 (mean: 4.20). There were no differences among p53 and the mean levels of proliferating cell nuclear antigen labeling index or p53 and the number of apoptotic bodies. CONCLUSIONS: A high index of proliferation has been shown in the patients studied. Positivity of p53 was seen in less than a half of the patients (35.71%). The index of apoptotic bodies observed was very low. Our results suggest that high-grade proliferation is not associated with increase of apoptosis in hepatocellular carcinoma.     

Adenoma of the minor papilla associated with pancreas divisum

Tumors of the minor papilla of the duodenum are quite rare. We report the first documented case of an adenoma of the minor papilla complicating pancreas divisum. A 52-year-old woman was admitted to our hospital for treatment of an asymptomatic duodenal tumor detected by computed tomography scan. Endoscopy showed an 18-mm, whitish-colored, sessile mass located in the descending duodenum proximal to a normal appearing major papilla. Endoscopic retrograde pancreatography revealed divisum of the pancreas with dilatation of pancreatic duct ranged in the dorsal pancreas. Transduodenal minor papillectomy was performed because there is malignant potential of the tumor and the possibility of acute pancreatitis. The Santorini orifice was then re-approximated to the duodenal wall for protection against acute pancreatitis caused by scarring and stenosis of the duct orifice as a possible late complication. The patient's postoperative course was uneventful and she has been asymptomatic without evidence of tumor recurrence or stenosis of the Santorini orifice on endoscopic examination for the last 4 years.     

Aberrant p53 expression and the development of gallbladder carcinoma and adenoma

Gallbladder carcinoma (GBC) is a highly lethal but relatively rare neoplasm of the digestive tract. The progression from gallbladder adenoma to carcinoma remains unclear. The p53 gene is the most frequently mutated tumor suppressor in human cancers. In this study, we analyzed the expression patterns of the p53 protein in 22 cases of GBC, 17 cases of precursor lesions (16 gallbladder adenomas and 1 cystadenoma), and 15 cases of normal epithelia using immunohistochemical analysis. The results were correlated with clinicopathologic characteristics. We found that p53 expression was significantly increased in 59.1% (13/22) of GBC cases and in 17.6% (3/17) of gallbladder adenoma cases (p = 0.009). There was no p53 expression in the 15 cases of normal epithelia, and a significant difference was shown between normal epithelium and GBC cases (p < 0.001). In addition, the expression pattern of p53 protein did not show any significant correlation with the histologic type and the differentiation grade of GBC. In conclusion, we suggest that the aberrant p53 expression may play a role in the occurrence of GBC.     

bcl-2与p53在大肠腺瘤和大肠癌中的表达

目的探讨原癌基因ｂｃｌ２与抑癌基因ｐ５３在大肠腺瘤和大肠癌中的表达变化与大肠腺瘤和大肠癌的发生、发展的关系，以及ｂｃｌ２与ｐ５３在大肠癌中的表达变化与大肠癌的临床病理特征间的关系．方法采用免疫组化ＡＢＣ法，分别检测ｂｃｌ２在３３例大肠腺瘤和４７例大肠癌中的表达变化和ｐ５３在４０例大肠腺瘤和６３例大肠癌中的表达变化．结果ｂｃｌ２在大肠腺瘤和大肠癌中的阳性表达分别为７２７％（２４／３３）和３４０％（１６／４７）．ｐ５３在大肠腺瘤和大肠癌中的阳性表达分别为４５０％（１８／４０）和８４１％（５３／６３），ｂｃｌ２和ｐ５３在大肠腺瘤和大肠癌中的表达有显著性差异（Ｐ＜００１），但其表达变化与大肠癌的临床病理特征关系不明显（Ｐ＞００５）．结论ｂｃｌ２表达在腺瘤向癌的演变过程中丢失，而ｐ５３表达则增加（Ｐ＜００１），表明它们参与了肿瘤生长和发展的共同通道，在大肠癌的发生、发展和演变过程中起着重要作用     

Endoscopic resection of adenoma of the minor papilla

Tumors of the minor papilla of the duodenum are rare. We successfully and safely treated a 16 mm sessile adenoma of the minor papilla using endoscopic resection. Endoscopic retrograde cholangiopancreatography (ERCP) yielded a normal cholangiopancreatogram with blind termination of the duct of Santorini in the minor papilla. We recommend endoscopic resection and histological examination of the entire lesion for adenomas of the minor papilla in patients without pancreas divisum.     

胃癌组织P53蛋白和PCNA的表达意义

目的研究胃癌组织Ｐ５３蛋白和增殖细胞核抗原（ＰＣＮＡ）的表达意义．方法应用ＡＢＣ免疫组织化学技术检测７６例保存资料完整并经病理学证实的胃癌石蜡包埋组织和３０例正常胃粘膜Ｐ５３蛋白及ＰＣＮＡ的表达进行同步检测．结果正常胃粘膜无Ｐ５３蛋白表达，而６４４％（４９／７６）胃癌组织中Ｐ５３蛋白表达阳性，Ｐ５３蛋白表达阳性者其细胞增殖活性为８２１％±１７６％，明显高于Ｐ５３蛋白表达阴性组的６４２％±１４３％（Ｐ＜００１）．Ｐ５３蛋白阳性率和ＰＣＮＡ计数值与胃癌临床分期及复发呈正相关（Ｐ＜００１）．结论联合检测Ｐ５３蛋白和ＰＣＮＡ对胃癌诊断、分期及预后有重要价值．     

非小细胞肺癌组织中MinaS3、p53、PCNA的表达及意义

目的 探讨Mina53在非小细胞肺癌中的作用及Mina53、p53、增殖细胞核抗原（PCNA）在其中联合表达的意义。方法用免疫组化S-P法检测34例非小细胞肺癌组织,10例正常肺组织中Mina53、p53、PCNA的表达。结果在正常肺组织中Mina53、p53、PCNA表达量都很少,而在非小细胞肺癌组织中均高度表达。在非小细胞肺癌组织中,Mina53的阳性表达率是52．94％（18／34）,其表达与临床病理分型、淋巴结转移有明显的相关性（P〈0．05）。p53、PCNA的阳性表达率分别是64．71％（22／34）、76．47％（26／34）,其与各临床病理参数均无相关性（P〉0．05）。Mina53、p53、PCNA在非小细胞肺癌组织中的表达两两之间均有相关性（P均〈0．01）。结论Mina53有可能成为非小细胞肺癌的标记物,Mina53与p53、PCNA在非小细胞肺癌中联合检测,可起到互补作用,较全面地反映非小细胞肺癌肿瘤细胞的增殖情况。     

Three cases of villous adenoma of the Vater papilla

A series of three cases of villous adenoma of the papilla of Vater is reported. In two cases, the pathological diagnosis made before, during and after surgery was of benign villous adenoma. In the third case, the diagnosis made before and during surgery was of adenoma but in the postsurgical examination a macro-invading carcinoma was found. Further endoscopic exploration revealed a recurrent villous adenoma and further surgery was carried out. Total resection, rather than a duodenopancreatectomy, was performed due to the length of time from detection of the recurrence until the second operation as well as to the small size of the recurrent tumor in the surgical examination.     

Endoscopic management of adenoma of the major duodenal papilla

BACKGROUND: It is well established that adenoma of the major duodenal papilla has a potential for malignant transformation. Standard treatment has been surgical (duodenotomy/local resection, pancreaticoduodenectomy). Endoscopic management is described, but there is no established consensus regarding the approach to papillectomy or the need for surveillance. This study describes endoscopic management and long-term follow-up of papillary tumors by 4 groups of expert pancreaticobiliary endoscopists. METHODS: Consecutive patients with papillary tumors referred to 4 pancreaticobiliary endoscopy centers for evaluation for endoscopic papillectomy were reviewed. For each patient, an extensive questionnaire was completed, which included 19 preoperative and 15 postoperative data points. A total of 103 patients (53 women, 50 men, age range 24-93) who underwent attempted endoscopic resection were included. Of these, 72 had sporadic adenoma, and the remaining patients had familial adenomatous polyposis, including Gardner's variant. Presenting symptoms were jaundice/cholangitis/pain (n=59), pancreatitis (n=18), and bleeding (n=12). Twenty-six patients were asymptomatic. RESULTS: Endoscopic treatment was successful, long term, in 83 patients (80%) and failed (initial failure or recurrent tumor) in 20 (20%) patients. Success was significantly associated with older age (54.7 [16.6] vs. 46.6 [21.7] years; p=0.08) and smaller lesions (21.1 [8.3] vs. 29.7 [7.2] mm; p<0.0001). Success rate was higher for sporadic lesions compared with genetically determined lesions (63 of 72 [86%] vs. 20 of 31 [67%]; p=0.02). There were 10 initial failures, which was more common for sporadic lesions (7 of 10). The overall success rate for papillectomy was similar in patients who had adjuvant thermal ablation (81%) compared with those who did not (78%). However, recurrence (n=10) was more common in the former group (9 of 10, [90%]; p=0.22). Complications (n=10) included acute pancreatitis (n=5), bleeding (n=2), and late papillary stenosis (n=3). Acute pancreatitis was more common in patients who did not have pancreatic duct stents placed (17% vs. 3.3%). Papillary stenosis was more frequent without short-term pancreatic duct stent placement (15.4% vs. 1.1%), although the difference was not statistically significant, because this complication was infrequent. CONCLUSIONS: Endoscopic treatment of papillary adenoma in selected patients appears to be highly successful. The majority can undergo complete resection after ERCP. In expert hands, complications are infrequent and may be avoided by routine placement of a pancreatic duct stent.     

大肠小扁平腺瘤、息肉样腺瘤p53、p21表达的研究

目的:观察大肠小扁平腺瘤p53、p21基因的表达,探讨小扁平腺瘤与息肉样腺瘤生物学行为的不同及其与大肠癌的关系.方法:利用免疫组化法研究50例小扁平腺瘤(A组)和30例息肉样腺瘤(B组)以及20例正常大肠黏膜(C组)的p53、P21基因表达情况.结果:p53、p21 在A、B、C 三组中阳性率分别为58%、56%;33.3%、36.7%;5%、10%.P53阳性率三组间差异有显著性(P＜0.05).p21阳性率:A、B组分别与C组有差异显著性(P＜0.05);A组高于B组,但卡方检验P＞0.05,无统汁学差异;A组进一步与B组中直径＜1.0cm的腺瘤的p21阳性率(30%)比较,差异有显著性(P＜0.05).结论:大肠小扁平腺瘤p53、p21基因的异常表达提示小扁平腺瘤的生物学行为与息肉样腺瘤有差别,可能更易于恶变.     

青老年人胃癌P53及增殖细胞核抗原表达的对比

目的通过对老人青年胃癌中ｐ５３及增殖细胞核抗原（ＰＣＮＡ）表达的研究，探讨青老年人胃癌临床表现的分子生物学异同．方法应用过氧化物酶标记的链霉卵白素（ＳＰ）染色法对６５例胃癌（青年组３５例，≤３５岁；老年组３０例，≥６０岁）进行ｐ５３蛋白及ＰＣＮＡ的免疫组织化学染色．并对胃癌细胞中ＰＣＮＡ阳性颗粒进行图象分析．结果ｐ５３和ＰＣＮＡ在青年人胃癌中的阳性率分别为６５７％和９４３％，均显著高于老年人（２６７％和５００％，Ｐ＜００１）．青年人胃癌中ＰＣＮＡ阳性颗粒平均光密度及积分光密度均显著高于老年人（Ｐ＜００５）．结论ｐ５３及ＰＣＮＡ的高表达可能是青年人胃癌恶性度高，进展快，预后差的原因     

肝细胞癌形成门静脉癌栓与P53,PCNA表达的关系

作者检测９９例手术切除的肝细胞癌（ＨＣＣ）中Ｒ５３蛋白和ＰＣＮＡ的表达。９９例中合并肉眼下门静脉癌栓（ＴＴＰＶ）３９例，合并镜下ＴＴＰＶ３０例，无ＴＴＰＶ３０例。总体Ｒ５３表达阳性率为２４．２４％，ＰＣＮＡ标记指数（ＰＣＮＡＬＩ）为３４．６±２３．６。在上述三组中，Ｐ５３表达阳性率、ＰＣＮＡＬＩ差异均有显著性，ＰＣＮＡＬＩ与Ｒ５３表达密切相关，Ｐ５３表达阳性的ＨＣＣ，其ＰＣＮＡＬＩ显著高于Ｐ５３表达阴性者。结果提示，Ｐ５３基因突变，ＰＣＮＡ活性增强，ＨＣＣ增殖水平由此而升高，可能是ＨＣＣ细胞获得更强侵袭性的重要机制之一，因而也是ＴＴＰＶ形成的机制之一。     

大肠癌组织nm23-HI p53 PCNA的表达

目的研究大肠癌组织ｎｍ２３ＨＩ，ｐ５３，ＰＣＮＡ的表达意义及其与肿瘤浸润转移的关系．方法１９９１年３月～１９９６年５月采用免疫组织化学方法检测７４例（男３９例，女３５例，平均年龄５３２岁，术前未做化疗及放疗）大肠癌组织（石蜡切片，厚４μｍ）中ｎｍ２３Ｈ１，ｐ５３，ＰＣＮＡ以及Ⅳ型胶原的表达情况．结果大肠癌ｎｍ２３Ｈ１，ｐ５３，ＰＣＮＡ的阳性率分别为７１６％、５２７％和８１１％．ｎｍ２３Ｈ１低表达与淋巴结转移有关（Ｐ＜００５），在Ⅳ型胶原表达不同的肠癌中ｎｍ２３－Ｈ１的表达无明显差异；ｐ５３和ＰＣＮＡ过表达与浸润程度和淋巴结转移有关（Ｐ＜００５）．结论ｎｍ２３ＨＩ低表达可作为预测大肠癌转移的较好指标．ｐ５３过表达在浸润转移过程及细胞增殖中均起重要作用．     

萎缩性胃炎中P53和PCNA的表达

目的了解Ｐ５３，ＰＣＮＡ在胃粘膜癌前病变中的表达意义．方法慢性萎缩性胃炎（ＣＡＧ）８９例，慢性浅表性胃炎（ＣＳＧ）２０例和胃腺癌２０例，作ＳＰ法观察Ｐ５３和ＰＣＮＡ的表达．结果Ｐ５３在ＣＳＧ和ＣＡＧ的单纯型、增生型和肠化型中不表达，异型性型中阳性表达率为１９０％（４／２１）．ＰＣＮＡ在ＣＳＧ和ＣＡＧ的单纯型、增生型、肠化型中无显著性差异（Ｐ＞００５）；而ＣＡＧ的异型性阳性细胞明显增多（Ｐ＞００１）．结论Ｐ５３表达与胃粘膜向癌的演变有关．ＰＣＮＡ随细胞增生活跃程度递增．二者结合对胃癌前病变的诊断、分级、治疗、预后有辅助价值．     

Endoscopic papillectomy and KRAS expression in the treatment of adenoma in the major duodenal papilla

Abstract

Objective. The use of endoscopic papillectomy for resecting adenomas in the major duodenal papilla is increasing. This study focuses on the following three issues: Can endoscopic papillectomy be performed as a safe diagnostic and/or therapeutic procedure in biopsy-verified or suspected ampullary adenoma? Does expression of mutated KRAS in resected adenomatous tissue predict long-term outcome? What other factors may affect long-term outcome and should, therefore, be considered in decision making prior to endoscopic papillectomy? Material and methods. Thirty-six prospectively collected patients who underwent endoscopic papillectomy at Karolinska University Hospital between 2005 and 2014 were analyzed. Results. The rate of exact agreement between the histomorphological grading of the endoscopic biopsies and the papillectomy specimens was low (48%). Obstructive jaundice at presentation increased the risk of undetected adenocarcinoma (RR = 3.98; 95% CI = 1.46–10.85, p = 0.007). Lesions with malignancies were significantly larger (mean 30.6 mm) than those where only adenomas were found (mean 14.4 mm, p = 0.001). Mutated KRAS was detected in 9 of the 36 post-papillectomy specimens, including 4 of the 5 cases of ampullary adenocarcinoma. Eighteen cases were endoscopically cured after a mean follow-up period of 47 months (range 16–92 months). Conclusions. Endoscopic papillectomy is a valuable staging tool because of the limitations of endoscopic biopsy. Endoscopic papillectomy concomitantly offers a curative treatment for most patients with adenoma in the major duodenal papilla. Jaundice at presentation and large adenomas may indicate the presence of more advanced disease. Determination of mutated KRAS seems to be of limited value in predicting long-term outcome.     

Expression of nitric oxide synthase in human gastric carcinoma and its relation to p53, PCNA

AIM: To investigate the expression of NOS in gastric carcinoma, and to explore the relationship between the expression of nitric oxide synthases (NOS) and p53, PCNA, pathological features and clinical staging of gastric cancer. METHODS: The activity of NOS protein was investigated in 85 samples of human gastric carcinoma and 25 samples of normal gastric mucosal tissue by biochemical assay. We then examined the expression of NOS, p53, PCNA in 85 samples of human gastric cancer was examined by immunohistochemistry, and NOS mRNA expression in 85 gastric cancer tissue specimens by In situ hybridization. RESULTS: Biochemical assay showed that the activity of NOS was significantly higher in gastric carcinoma than in normal gastric mucosal tissues (t=0.4161, P＜0.01). Immunohistochemistry revealed that endothelial nitric oxide synthase (eNOS) expressed in all samples of normal gastric mucosa, but only 6 cases of 85 gastric cancer specimens showed weak positive immunohistochemical reactions to eNOS (20%). Inducible nitric oxide synthase (iNOS) was expressed strongly in human gastric carcinoma (81.2%). In situ hybridization analysis showed that iNOS mRNA expression was significantly stronger than eNOS mRNA expression in gastric cancer tissue (X~2 = 10.23, P＜0.01). The expression of iNOS in gastric cancer was associated with differentiation, clinical stages or lymph node metastases (r=0.3426,P＜0.05). However, iNOS expression did not correlate with histological classifications and morphological types. The expression of iNOS was significantly correlated with p53 or PCNA expression (r=0.3612, P＜0.05). The expression of neuronal nitric oxide synthase (nNOS) was not examined by immunohistochemistry and in situ hybridization in gastric cancer specimens and normal gastric mucosa. CONCLUSION: In human gastric cancer, there is an enhanced expression of iNOS, but not of eNOS. NOS promotes the proliferation of tumor cells and plays an important role in gastric cancer spread. Inactivation of antioncogene p53 and overexpression of iNOS might play a synergetic role in the process of carcinogenesis of human gastric carcinoma.