大肠肿瘤细胞凋亡及相关基因表达的研究

为了探讨Ｂｃｌ－２和Ｐ５３蛋白在大肠肿瘤中的表达及与细胞凋亡的关系，用免疫组化方法观察了４５例大肠腺瘤和６１例大肠癌中Ｂｃｌ－２和Ｐ５３蛋白的表达。正常大肠粘膜中Ｂｃｌ－２和Ｐ５３均未见表达，而大肠腺瘤及大肠癌阳性率均较正常明显增加（Ｐ〈０．０１）。大肠腺瘤Ｐ５３表达随腺瘤大小增加而增加，其中≥２０ｍｍ组阳性率（７７．７８％）显著高于〈１０ｍｍ组（３５．００％，Ｐ〈０．０５）。Ｐ５３蛋白阳性率也随     

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．     

P^53及nm23基因异常表达与肝细胞肝癌临床,病理的关系

用免疫级化方法检测了２７例肝细胞肝癌患者癌组织Ｐ＾５３及ｎｍ２３基因异常表达，结果Ｐ＾５３及ｎｍ２３基因异常表达率分别为６６．６７％和５９．２６％。Ｐ＾５３及ｎｍ２３基因异常表达与患者血清ＡＦＰ阳性有关（Ｐ〉０．０５），与存在门静脉癌栓有关（Ｐ〈０．０５）。提示Ｐ＾５３及ｎｍ２３基因异常表达与患者预后有关，对肝细胞肝癌患者检测Ｐ＾５３和ｎｍ２３基因可预测其预后。     

胃癌组织P16，P53蛋白和增殖细胞核抗原的表达意义

目的探讨Ｐ１６,Ｐ５３蛋白和增殖细胞核抗原（ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｎｕｃｌｅａｒａｎｔｉｇｅｎ,ＰＣＮＡ）在胃癌的发生、发展中的作用及临床意义．方法应用免疫组织化学方法,对７７例胃癌和癌旁粘膜组织、２１例胃正常组织中Ｐ１６,Ｐ５３蛋白表达产物和ＰＣＮＡ进行检测,并结合临床资料进行分析．结果胃癌组织中Ｐ１６蛋白的阳性率为２０８％（１６／７７）,明显低于癌旁粘膜组织５９７％（４６／７７）和胃正常组织９０５％（１９／２１,Ｐ＜００５）;Ｐ５３蛋白与ＰＣＮＡ在胃癌组织中的阳性率为８０５％（６２／７７）和９２２％（７１／７７）,明显高于癌旁粘膜组织４１６％（３２／７７）,６４９％（５０／７７）和胃正常组织００％（０／２１,Ｐ＜００５）．Ｐ１６,Ｐ５３蛋白和ＰＣＮＡ阳性表达与胃癌组织学类型、浸润深度、分化程度及淋巴结转移有显著性差异（Ｐ＜００５）,与患者年龄、性别、肿瘤大小及部位无关（Ｐ＞００１）．结论Ｐ１６,Ｐ５３蛋白和ＰＣＮＡ的异常表达对胃癌的发生发展、恶性程度、淋巴结转移及预后有密切关系和重要临床意义．     

p53蛋白在胆囊腺癌中的表达及意义

应用免疫组织化学Ｓ．Ｐ法检测了４２例胆中腺癌和８例胆囊腺瘤中Ｐ５３蛋白的表达情况。结果显示，胆囊腺癌中Ｐ５３阳性率为４７．６％，胆囊腺瘤及癌旁正常粘膜阳性率均为０％，与胆囊腺癌比较，差异有显著性。     

大肠良恶性病变p53基因表达及意义

目的研究抗癌基因Ｐ５３蛋白在大肠良、恶性病变组织中的表达情况，探讨Ｐ５３蛋白表达与大肠癌临床病理因素的关系．方法应用免疫组织化学ＳＰ法检测了１４６例良恶性大肠病变组织中Ｐ５３蛋白水平．结果正常大肠粘膜及非肿瘤性息肉Ｐ５３蛋白均阴性，而１１例腺瘤，５３例癌旁粘膜及７６例癌组织中ｐ５３阳性率分别为１８１８％（２／１１），１３２１％（７／５３）及４２１１％（３２／７６）．在腺瘤及癌旁粘膜组织中，仅有散在细胞核里ｐ５３阳性，但在３２例ｐ５３阳性大肠癌中，７５％呈现（＋＋）或（＋＋＋）的阳性表达．在各组织类型癌中，以低分化腺癌与粘液癌ｐ５３阳性率最高，分别为６３６４％（７／１１）及６２５％（１０／１６），显著高于高中分化腺癌的３０１６％（１５／４０）（Ｐ＜００５），并且ｐ５３阳性大肠癌比ｐ５３阳性癌更容易穿透肠壁侵犯浆膜及浆膜外组织，其淋巴结转移率也明显高于ｐ５３阴性者（Ｐ＜００５）．但Ｐ５３蛋白表达与肿瘤大小，肉眼类型，部位，Ｄｕｋｅｓ分期及术后３年生存率无关．结论ｐ５３基因突变或过表达是大肠肿瘤发生过程中的重要因素，并可能与肿瘤进展及转移有关．     

胆囊腺癌p21、p53表达及细菌L型检测的意义

应用免疫组化（ＳＰ法）和革兰氏染色技术，对３６例胆囊胆癌和３０例慢性胆囊炎进行ｐ２１、ｐ５３蛋白及细菌Ｌ型检测，同时对Ｌ型阳性和阴性组织的ｐ２１、ｐ５３表达进行对比分析。结果发现，腺癌和慢性炎的革兰染色Ｌ型检出率分别为８０．６％和７６．７％，与Ｌ型抗原检出率均地 差异。腺癌组的Ｐ２１、Ｐ５３表达率明显高于炎症组，腺癌中Ｌ型阳性组的Ｐ２１、Ｐ５３表达率也高于其Ｌ型阴性组，表明Ｌ型感染与胆囊腺癌、慢性     

肺鳞癌组织Mdm2蛋白表达p53基因突变相关性研究

目的探讨原发性肺鳞癌与Ｍｄｍ２蛋白表达、ｐ５３基因突变之间的相关性。方法采用ＳＰ免疫组织化学方法和银染聚合酶链式反应单链构象多态性（银染ＰＣＲＳＳＣＰ）方法检测手术切除、经病理证实的４５例原发性肺鳞癌组织及癌旁肺组织中Ｍｄｍ２蛋白表达和ｐ５３基因突变情况。结果免疫组织化学检测的４５例肺鳞癌组织Ｍｄｍ２蛋白阳性率为６２％（２８／４５）,２例癌旁肺组织中Ｍｄｍ２蛋白呈弱阳性表达,免疫组织化学方法结合银染ＰＣＲＳＳＣＰ检测４５例肺癌组织ｐ５３基因突变,阳性率为５１％（２３／４５）,４５例癌旁肺组织未检测到ｐ５３基因突变。（１）肺鳞癌与ｐ５３基因突变有明显相关性（Ｐ＜０．０５）。（２）肺鳞癌与Ｍｄｍ２基因产物过度表达有明显相关性（Ｐ＜０．０５）。（３）Ｍｄｍ２蛋白过度表达与ｐ５３基因突变复合存在和肺鳞癌淋巴转移（６６％,１０／１５）有明显相关性（Ｐ＜０．０５）。结论Ｍｄｍ２蛋白过度表达与ｐ５３基因突变是临床估计患者预后重要的分子生物学指标     

细胞间粘附分子-1在肝癌组织的表达及意义

目的：研究细胞间粘附分子－１（ＩＣＡＭ－１）在原发性肝癌的临床意义。方法：以免疫线化方法结合全自动图像分析检测ＩＣＡＭ－１在３０例原发性肝癌组织及６例正常肝组织的表达,分析其与肿瘤分化程度、大小及转移之间的关系。结果：３０例原发性肝癌组织２５例ＩＣＡＭ－１表达阳性（阳性率８３．３％）,肝癌组织中ＩＣＡＭ－１含量明显高于正常肝组织（Ｐ〈０．０１）,转移组肝癌中ＩＣＡＭ－１含量明显地无转移组（Ｐ〈０．     

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     

结肠癌及癌前病变组织中COX-2及VEGF的表达

目的: 探讨结肠癌及癌前病变中COX-2和血管内皮生长因子(VEGF)的表达意义.方法:应用免疫组织化学ABC法检测COX-2及VEGF在40例癌旁正常结肠黏膜和结肠癌、27例结肠腺瘤组织中COX-2和VEGF的表达.结果: 结肠腺瘤和结肠癌组COX-2阳性表达率明显高于癌旁正常结肠黏膜组(63.0%, 77.5% vs 0.0%, 0.0%;P<0.05). 结肠腺瘤和结肠癌组VEGF阳性表达率明显高于癌旁正常结肠黏膜组(70.4%, 80.0% vs 25.0%, 25.0%;P<0.05), 且二者表达有相关性(r = 0.411, P<0.01). 结论:COX-2和VEGF在结肠腺瘤及结肠癌中表达异常增高.     

Endoscopic identification and quantification of aberrant crypt foci in the human colon

BACKGROUND: Aberrant crypt foci may be precancerous lesions in the human colon. The occurrence of aberrant crypt foci was compared in patients with an endoscopically normal colon, known adenomatous polyps, and known colorectal cancer. METHODS: In 90 patients (30 colonoscopically normal, 30 with adenomatous polyps, 30 with colorectal cancers) magnification chromoscopy was performed to identify aberrant crypt foci in the distal 10 cm of the rectum. Representative biopsy specimens were obtained for histopathologic assessment. RESULTS: Aberrant crypt foci were readily identified. Median and (mean) numbers of aberrant crypt foci were as follows: endoscopically normal colon, 3.5 (5.0); adenomatous polyp(s), 4.0 (6.9); and colorectal cancer, 7.5 (9.9). The number of aberrant crypt foci detected was significantly associated (p = 0.02) with an increased odds that a patient would be in the group with known colorectal cancer (odds ratio = 1.11; 95% CI [1.02, 1.21]), but not in any other group. CONCLUSIONS: Despite a stepwise increase in the number of aberrant crypt foci across the 3 groups, aberrant crypt foci was significantly associated only with comorbid colorectal cancer. Aberrant crypt foci was not associated with adenomatous polyp(s) or normal colon. Additional studies are needed to further elucidate the role of aberrant crypt foci in the development of colorectal neoplasia in humans.     

老年人大肠息肉的临床分析

目的 探讨老年人大肠息肉的临床特点及其与癌变的关系。方法 对我院经结肠镜检出的158例老年大肠息肉患者的临床特点进行回顾性分析，对其中120例进行1－6年（平均4．5年）的结肠镜随访，并与青中年组的437例患者相对照。结果 老年人大肠息肉的检出率、癌变率分别为30．0％及23．4％，均显著高于中青年组的10．2％及6．9％（P＜0．01），随年龄增长检出率有逐渐增加的趋势。分布以直肠和乙状结肠多见，但升结肠的癌变率（37．5％）明显高于左半结肠（14．3％，P＜0．05），且直肠、降结肠、横结肠及升结肠的癌变率也显著高于青中年组的同一部位（P＜0．01）；病理类型以腺瘤性息肉为多，占77．6％，也明显高于青中年组的同一病理类型（P＜0．01）。37例癌变息肉均为腺瘤性息肉，其中绒毛状腺瘤的癌变率（56．9％）显著高于管状腺瘤（3．4％，P＜0．01）。息肉体积大（＞2cm)、基底宽、数量多，癌变率高。腺瘤性息肉经内镜下摘除者其癌变率明显低于未摘除者（P＜0．01）。结论 老年人大肠息肉中的腺瘤性息肉的大小、形态、数量及病理类型是其癌变的主要危险因素，老年人应尽量行全结肠检查，检出大肠息肉者应尽可能首选肠镜下摘除，定期随访，减少癌变的机会。     

胰腺癌组织中p53、血管内皮生长因子的表达与血管生成的关系及其临床意义

目的 探讨胰腺癌组织中p53、血管内皮生长因子(VEGF)和血管生成的关系。方法 用免疫组织化学方法检测48例胰腺癌组织及癌旁组织、6例正常胰腺组织中p53、VEGF表达和微血管密度(MVD)。结果 胰腺癌组织中VEGF、p53的阳性表达率分别为54.17％和50％,显著高于癌旁组织及正常组织的表达率(P<0.01),胰腺癌组织中MVD显著高于癌旁组织及正常组织。VEGF表达与肿瘤大小和分期有关(P=0.038,P=0.045),VEGF表达与MVD有相关性(r=0.294 P=0.043)。p53与淋巴结转移及预后相关(P<0.05)而与VEGF、MVD之间无关。MVD与胰腺癌临床病理特征无关,MVD与生存期存在负相关(r=0.371 P=0.011)。多元回归分析显示p53、VEGF和MVD都不是影响胰腺癌预后的独立因素。结论 p53基因突变为胰腺癌分子事件的晚期事件,可作为评价胰腺癌预后的一项指标,抗血管生成可能有利于胰腺癌的治疗。     

Multiple Large Hyperplastic Polyps of the Colon Coincident with Adenocarcinoma

Diminutive hyperplastic polyps are the most common non-neoplastic lesions of the colon. Typically, they are small (<0.5 cm) sessile lesions, lack cellular atypia, and are found predominantly in the rectosigmoid region of the colon. Multiple large hyperplastic polyps (>1 cm) are rare. Although the relationship between diminutive hyperplastic polyps and adenomatous polyps or carcinoma is controversial, even less data are available on the significance of large hyperplastic polyps. We report the case of a 56-yr-old man who was seen because of fatigue, anemia, and Hemoccult-positive stool. On air contrast barium enema study and colonoscopy, multiple polyps that were similar in appearance were found distributed symmetrically throughout the colon. However, histologic examination revealed 16 hyperplastic polyps 1–2 cm in size, multiple diminutive hyperplastic polyps, one adenomatous polyp, and one adenomatous polyp containing well-differentiated adenocarcinoma. Because multiple large hyperplastic polyps are rare, we suspect this entity may be distinct from diminutive hyperplastic polyps. In our patient, large hyperplastic polyps were distributed symmetrically throughout the colon and were associated with a synchronous carcinoma. Because large hyperplastic polyps may be coincident with adenomatous polyps and carcinoma of the colon, we recommend that patients found to have large hyperplastic polyps undergo removal of all polyps for histologic study.     

Isolation and sequencing of a novel tropomyosin isoform preferentially associated with colon cancer

BACKGROUND & AIMS: Nonmuscle human tropomyosin (hTM) isoforms have distinct functions and may play important roles in various disease processes. METHODS: In an attempt to identify colon epithelial tropomyosin isoform, a complementary DNA library prepared from a human colon cancer cell line T84 was screened by an oligonucleotide probe complementary to messages of all known hTM isoforms. A novel clone called TC22 was obtained. The amino acid sequence of TC22 isoform is identical to isoform 5 (hTM5) apart from the C terminal domain, amino acids 222-247 coding the exon 9. RESULTS: Northern blot analysis showed that TC22 message is expressed in transformed epithelial cell lines and tumor tissues but not in normal epithelial cells. We developed a monoclonal antibody specific to TC22 isoform (TC22-4). By Western blot and immunoperoxidase assays, we analyzed 105 colonic specimens (fresh frozen and formalin fixed) from 96 patients with colon polyps (hyperplastic) or adenomas with or without dysplasia and cancer. Twenty-one of 22 (95%) of colon cancer specimens showed the presence of TC22, compared with only 1 of the 17 normal colon specimens and none of the 13 hyperplastic polyps (P < 0.0001). As assayed by immunoperoxidase staining, TC22 expression progressively increased in benign adenomatous polyps (35%) and polyps with mild and severe dysplasia (57% and 100%, respectively). CONCLUSIONS: We cloned and sequenced a novel hTM isoform, TC22, which is strongly associated with colonic neoplasia and carcinoma. TC22 may provide a useful biomarker for surveillance of colon cancer.     

The association of fasting insulin concentrations and colonic neoplasms in acromegaly: a colonoscopy-based study in 210 patients

CONTEXT: Hyperinsulinemia is associated with colon carcinoma in the general population. Patients with acromegaly are considered to be at risk for developing colonic lesions and typically have hyperinsulinemia. OBJECTIVE: Our objective was to evaluate the role of fasting insulin levels on the prevalence of colonic adenomatous polyps or adenocarcinoma in acromegaly. DESIGN: This is an analytical, observational, prospective study. Patients: A total of 210 patients (111 women, 99 men, age 20-82 yr) undergoing complete colonoscopy at diagnosis of acromegaly were included in this study. RESULTS: Colonic lesions were found in 81 patients (38.6%), and consisted of hyperplastic polyps in 33 (15.7%), adenomatous polyps in 42 (20.0%), and adenocarcinoma in six patients (2.8%). Polyps were single in 22 cases (27.1%). Fasting insulin levels were significantly lower in patients without lesions (16.0 +/- 7.5 mU/liter) than in patients with hyperplastic polyps (22.4 +/- 8.8 mU/liter; P < 0.01), adenomatous polyps (38.0 +/- 15.9 mU/liter; P < 0.0001), and adenocarcinoma (59.0 +/- 30.6 mU/liter; P < 0.0001). Fasting insulin levels were also lower in patients with hyperplastic polyps than in those with adenomatous polyps (P < 0.01). The odds ratio for harboring colonic adenomas was 14.8 (95% confidence interval 4.4-51.2; P < 0.0001) and 8.6 times higher (95% confidence interval 2.8-29.0; P < 0.0001) in patients with fasting insulin levels in the upper tertile [>/=27.1 mIU/liter (n = 28)] compared with the lower [12.1 to <27.1 mIU/liter (n = 74)], respectively. CONCLUSION: An increase in fasting insulin levels is associated with an 8.6- to 14.8-fold increased risk of presenting with colonic adenomas in acromegaly.     

No evidence for overexpression of the p53 protein and mutations in exons 4–9 of the p53 gene in a large family with adenomatous polyposis

Objective: Familial adenomatous polyposis coli (FAP) is an autosomal dominant disease characterized by an early onset of numerous adenomatous polyps of the colon and a high risk of colon carcinoma. The role of the p53 gene in the multistage process of FAP is as yet poorly defined. In the present study, a large family with evidence of polyposis and colon cancer was screened for the mutations of the p53 gene and protein overexpression.
Methods: We examined p53 protein expression from individuals with immunohistochemical techniques using monoclonal antibody PAb1801. Polymerase chain reaction products of exons 4–9 of the p53 were examined from individuals by single strand, conformational polymorphism analysis.
Results: We could find no evidence of overexpression and mutations of the p53 in any lesion including adenomas and carcinomas.
Conclusion: We found that p53 gene alterations do not contribute to the genesis of adenoma or carcinoma of FAP patients for this large family examined.     

XAF1基因与p53基因在结直肠肿瘤中的表达研究

目的观察两个相邻位置的抑癌基因XIAP相关因子1(XAF1)与p53基因在结直肠肿瘤中的表达。方法选取结肠癌细胞株Colo205、Colo320、LoVo、SW1116为体外研究对象,另取41例结直肠癌、28例结直肠腺瘤/息肉以及31例正常人结肠黏膜为体内研究对象。应用逆转录聚合酶链反应检测XAF1mRNA与p53mRNA在体内外的表达,应用免疫组化法检测P53蛋白在结直肠组织中的表达。结果4种细胞株中XAF1表达均较为低下,p53mRNA表达均较高。结直肠肿瘤组织中的XAF1mRNA表达显著低于正常组织(P<0.01),结直肠癌中的表达又显著低于良性肿瘤(P<0.05)。结直肠肿瘤组织中的p53mRNA表达显著高于正常组织(P<0.01),但在良、恶性肿瘤中的表达差异无统计学意义(P<0.05)。P53蛋白在正常组织中未见表达,良、恶性肿瘤组的组织P53蛋白表达之间差异无统计学意义(P>0.05)。结论XAF1基因在结直肠肿瘤中表达降低,且结直肠癌XAF1mRNA表达显著低于良性肿瘤,可作为判断良、恶性肿瘤的鉴别指标。