胆囊癌与胆囊良性病变的关系

已经证明,许多良性病变与胆囊癌的发病有关,而胆囊癌患者中50％以上合并胆囊良性病变,具体有胆囊结石、胆囊息肉、胆囊腺瘤、慢性胆囊炎。     

胆囊良恶性病变组织中桩蛋白和碳酸酐酶Ⅸ表达及临床意义

目的 研究胆囊良恶性病变组织中桩蛋白(Paxillin)和碳酸酐酶Ⅸ(CAⅨ)表达水平及其临床病理意义.方法 108例胆囊腺癌、46例癌旁组织、15例腺瘤性息肉和35例慢性胆囊炎手术切除标本常规制作石蜡包埋切片,Paxillin和CAⅨ染色方法为EnVision免疫组化法.结果 胆囊腺癌Paxillin和CAⅨ表达阳性率(分别为60.2%和49.1%)明显高于癌旁组织(分别为26.1%、x2=15.00和23.9%、x2=8.41,P值均＜0.01)、腺瘤性息肉(分别为20.0%、x2=8.60、P＜0.01和20.0%、x2=4.49、P＜0.05)和慢性胆囊炎(分别为14.3%、x2=22.89和11.4%、x2=15.63,P值均＜0.01).Paxillin和CAⅨ表达阳性的良性病例的胆囊上皮均呈中至重度不典型增生.高分化腺癌、肿瘤最大径＜2 cm、无淋巴结转移、未侵犯周围组织的病例Paxillin和CAⅨ表达阳性率明显低于低分化腺癌、肿瘤最大径≥2 cm、淋巴结转移和侵犯周围组织的病例.经Kaplan-Meier生存分析发现Paxillin和CAⅨ表达阳性病例术后生存期明显低于阴性表达病例(x2=5.65、P＜0.05和5.65=5.92、P＜0.01);Cox多变量回归分析显示Paxillin和CAⅨ阳性表达均是反映胆囊腺癌预后不良的重要指标.结论 Paxillin和CAⅨ表达与胆囊腺癌发生、肿瘤生物学行为及预后有密切关系,Paxillin和CAⅨ阳性表达者预后不良.

Abstract：

Objective To study the expression and clinicopathological significance of Paxillin and CAⅨ in the benign and malignant lesions of gallbladder.Methods The surgical resected specimens of 108 cases of gallbladder adenocarcinoma, 46 cases of peritumoral tissue, 15 cases of adenomatous polyp and 35 cases of chronic cholecystitis were routinely made paraffin embedded sections.The expressions of Paxillin and CAⅨ were stained with Envision immunohistochemistry.Results The positive rates of Paxillin and CAⅨ expression was significantly higher in gallbladder adenocarcinoma (60.2% and 49.1%) than those in peritumoral tissues (26.1%, x2 =15.00, P ＜0.01 and 23.9%,x2=8.41,P ＜0.01), adenomatous polyp (20.0%,x2=8.60,P＜0.01 and 20.0%,x2 =4.49,P＜0.05) and chronic cholecystitis(14.3% ,x2 =22.89, P＜0.01 and 11.4%,x2 =15.63,P ＜0.01).All the gallbladder epithelia of the benign cases with Paxillin and CA Ⅸ positive expression showed moderate to severe atypical hyperplasia.The positive expression rates of Paxillin and CA Ⅸ were significanctly lower in the cases of well-differentiated, maximal diameter of mass less than 2 cm, no lymph nodes metastasis and no surrounding tissues invasion than those of the cases with poorly differentiated, maximal diameter of mass over 2 cm, lymph nodes metastasis and surrounding tissues invasion.With Kaplan-Meier analysis, it suggested that the survival period after the surgery in Paxillin and CAⅨ positive expression cases was shorter than that of negative expression cases (x2 = 5.65,P＜0.05,5.65=5.92, P＜0.01).With multivariate Cox regression analysis, it indicated that both Paxillin and CAⅨ positive expression was an important indicator of the poor prognosis in gallbladder adenocarcinoma.Conclusion The expression of Paxillin and CA Ⅸ may be closely related to the carcinogenesis, tumor biological behaviors, and prognosis of gallbladder adenocarcinoma.The positive expression of Paxillin and/or CAⅨ is associated with poor prognosis.     

胆囊胆汁CEA测定诊断胆囊良恶性病变的价值

作者测定４１例胆囊胆汁ＣＥＡ，胆囊结石与胆囊良性息肉胆汁ＣＥＡ水平均在５００ｎｇ／ｍ１以下，胆囊癌则超过５００ｎｇ／ｍｌ，其平均值高达前两者的３倍。作者认为胆囊胆汁ＣＥＡ测定可为临床诊断胆囊结石合并胆囊癌、胆囊息肉恶变提供一个较好的辅助诊断指标。     

胆囊良恶性病变组织中PARP和TRAP表达及其临床病理意义

目的研究胆囊良恶性病变组织中聚腺苷二磷酸核糖聚合酶（PARP）和抗酒石酸酸性磷酸酶（TRAP）表达水平及其临床病理意义。方法EnVsion^TM免疫组织化学法检测108例胆囊腺癌、46例癌旁组织、15例腺瘤性息肉和35例慢性胆囊炎组织中PARP和TRAP的表达。结果胆囊腺癌PARP和TRAP表达阳性率（57．4％、36．1％）明显高于癌旁组织（21．7％、4．3％）、腺瘤性息肉（6．7％、0）和慢性胆囊炎胆囊上皮（0、0）（P〈0．01）;PARP和TRAP表达阳性的良性病变胆囊上皮均呈不典型增生;高分化腺癌、肿块最大径〈2cm、无淋巴结转移及未侵犯周围组织病例PARP和TRAP表达阳性率均明显低于中或低分化腺癌、肿块最大径≥2cm、淋巴结转移及侵犯周围组织病例（P〈0．05或0．01）;胆囊腺癌中PARP和TRAP表达水平呈高度一致性（χ^2=7．17,P〈0．01）。结论PARP和TRAP表达水平可能是反映胆囊腺癌发生进展、临床生物学行为及预后的重要酶类标记物。     

胆囊切除对老年大肠腺瘤性息肉的影响

目的探讨胆囊切除对老年人大肠腺瘤性息肉(CAP)的影响。方法选择完成全结肠镜检查的60岁以上退休员工1 125例,分为CAP组(n=187)和正常对照组(n=938),并根据B超结果分为胆囊切除组和未切除组,对其肠镜结果、体质指数(BMI)、腰围、胆红素谱进行分析。结果男性CAP检出率明显高于女性(χ~2=13.210,P<0.001);CAP组年龄、腰围明显高于非CAP组(P<0.001);胆囊切除组的大肠腺瘤检出率明显高于未切除组(χ~2=5.348,P<0.021);经Logistic回归法分析提示性别、年龄、腰围、胆囊切除(P=0.019,OR=1.876,95%CI:1.118~3.146)是发生CAP的危险因素。结论胆囊切除可能是老年人患CAP的危险因素之一。     

经皮胆囊镜诊治胆囊小息肉病变24例分析

应用经皮胆囊镜检查及治疗胆囊小息肉病变２４例。通过胆囊镜检查可明确息肉性质，同时进行相应的治疗。对２０例定性为非肿瘤性息肉者行经皮胆囊镜息肉摘除术，未发生并发症。具有痛苦小，康复快，近期内临床效果较满意。作者认为胆固醇性息肉为其最佳适应证。４例定性为肿瘤性者，其中腺瘤３例、腺瘤内癌１例均中转胆囊切除术，得到及时的诊断和治疗。     

SR-BI在胆固醇息肉患者胆囊黏膜上皮中的表达

目的探讨SR-BI在胆囊胆固醇息肉患者胆囊黏膜中的表达和分布,了解其与胆固醇息肉发病之间的关系。方法应用免疫组化和westernblot方法检测SR-BI在15例胆固醇息肉患者胆囊黏膜(息肉组)和13例非胆囊疾病患者胆囊黏膜(对照组)标本中的表达。结果SR-BI表达于胆囊黏膜上皮细胞顶侧,息肉组的SR-BI表达(0.194±0.04)显著低于对照组的表达(0.364±0.07),其差异具有统计学意义(P(0.01)。结论胆固醇息肉患者胆囊黏膜上皮细胞中SR-BI表达减弱,提示其在胆固醇息肉患者胆汁胆固醇过饱和机制中起一定作用。     

胆囊息肉样病变612例临床分析

目的分析总结胆囊息肉样病变的临床、病理、诊断等特征．方法我院及中华医学会第七届全国胆道外科学术会议资料共报道胆囊息肉样病变６１２例进行分析和总结．结果胆囊息肉样病变６１２例占同期胆囊切除术的４２％；３０岁～５０岁占７８５％；结石合并率２８５％；病理类型中以胆固醇息肉最多，占５３７％；腺瘤性息肉恶变率极高，达２８５％；临床表现无特异性，Ｂ超的诊断率最高，达９２５％．结论胆囊息肉样病变患者相对年轻；病理类型以胆固醇类多见，腺瘤性息肉易恶变，特别是合并结石的息肉；临床诊断以Ｂ超为首选     

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.     

Expression of P53 oncoprotein in benign and malignant lesions of large bowel

AIM: To investigate the expression of P53 oncoprotein in benign and malignant lesions of the large bowel as well as the relationship between p53 expression and clinicopathological factors. METHODS: Immunohistochemistry was used to detect P53 protein in large bowel tissues of 146 cases with benign and malignant lesions. RESULTS: All normal large bowel mucosae and non-neoplastic polyps were negative for P53 protein. However, the positive rates of P53 protein in adenomas, paracancerous mucosae and carcinomas were 18.18% (2/11), 13.21% (7/53) and 42.11% (32/76), respectively. The P53 expression in both adenomas and paracancerous mucosae presented only weak staining, whereas 75% of p53 positive cancers displayed very intense staining (++ or +++). The rates of P53 protein detection in poorly differentiated carcinoma and mucous carcinoma were 63.64% (7/11) and 62.5% (10/16), respectively, which were much higher than that of well/moderately differentiated carcinomas (30.16%, 15/40) (p < 0.05), and the carcinomas with marked positive p53 expression were more likely to penetrate the bowel wall and metastasize to lymph nodes (p < 0.05). However, no relationship between p53 expression and massive type, tumor size, location, Dukes stage or 3-year survival was found in this study. CONCLUSION: P53 gene mutation and overexpression are common in colorectal cancers, and seem to be associated with histological type, progression and lymph node metastasis of colorectal cancer.     

溃疡性结肠炎相关性大肠癌P53、K-ras及hMSH2蛋白表达的研究

目的 探讨溃疡性结肠炎相关性大肠癌组织中P53、K-ras及hMSH2蛋白表达。方法 以溃疡性结肠炎伴不典型增生(UD)和溃疡性结肠炎相关性大肠癌(UCACRC)组织为实验组，溃疡性结肠炎(UC)和散发性大肠癌(SCRC)组织为对照组，应用免疫组化法检测组织中P53、K-ras、hMSH2蛋白的表达状况；聚合酶链式反应一单链构象多态性分析法(PCR-SSCP)检测组织中的微卫星不稳定性(MSI)状态(6个位点)，并进行统计学分析。结果 P53蛋白过表达的阳性率在UC(1／25例)与UD(3／7例)组间，UC与UCACRC(4／8例)组间差异均有统计学意义(P＜0．05，P＜0．01)，UCACRC与SCRC(17／30例)组间差异无统计学意义(P＞0．05)；突变型K-ras表达的阳性率在UC(4／25例)与UD(4／7例)组间，UC与UCACRC(7／8例)组间差异均有统计学意义(P＜0．05，P＜0．01)，UCACRC与SCRC(24／30例)组间差异无统计学意义(P＞0．05)；hMSH2蛋白缺失率在UC(2／25例)与UD(0／7例)组间、UD与UCACRC(4／8例)组间、UCACRC与SCRC(13／30例)组间差异均无统计学意义(P＞0．05)。MSI阳性率在UC(0／25例)与UD(3／7例)组间差异有统计学意义(P＜0．01)，在UD与UCACRC(2／8例)组间、UCACRC与SCRC(7／30例)组间差异无统计学意义(P＞0．05)。结论 P53、K-ras基因突变、MSI在UCACRC的发生发展过程中可能是一早期事件。UCACRC中MSI与hMSH2蛋白的缺失可能无关。     

Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary

AIM： To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary. METHODS： We examined 42 cases of gallbladder carcinoma： 22 Japanese and 20 Hungarian cases, p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of flve-microsatellite markers （BAT-25, BAT-26, D2S123, DSS346, and D17S250）. RESULTS： Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases （11/22 vs 6/18, P = 0.348）. Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant （0/11 vs 2/6,P = 0.110）. K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 （42.1%） ]apanese cases were MSI-high （presence of novel peaks in more than one of the five loci analyzed）, whereas only 1 of 15 （6.7%） Hungarian cases was MSI-high （P = 0.047）. CONCLUSION： It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.     

Expression of Ki-67, p53, and K-ras in chronic pancreatitis and pancreatic ductal adenocarcinoma

AIM: To examine surgical specimens of pancreas with either chronic pancreatitis or pancreatic cancer in order to study whether ductal hyperplasia and dysplasia in pancreas represent precursor lesions for pancreatic cancer. METHODS: We examined expression of Ki-67, CEA, p53, and K-ras, in the surgical specimens of pancreas with adenocarcinomas (n= 11) and chronic pancreatitis (n = 12). Cellular proliferation was assessed by Ki-67 proliferation index using the proliferation marker Ki-67. In specimens with pancreas cancer, we divided pancreas epithelium into normal (n = 7), ductal hyperplasia (n = 3), dysplasia (n = 4), and cancerous lesion (n = 11) after hematoxylin and eosin staining, Ki-67, and CEA immunohistochemical staining. In cases with chronic pancreatitis, the specimen was pathologically examined as in cases with pancreas cancer, and they were also determined as normal (n = 10), ductal hyperplasia (n = 4), or dysplasia (n = 5). p53 and K-ras expression were also studied by immunohistochemical staining. RESULTS: In pancreatic cancer, the Ki-67 index was 3.73±3.58 in normal site, 6.62±4.39 in ductal hyperplasia, 13.47±4.02 in dysplasia and 37.03±10.05 in cancer tissue, respectively. Overall, p53 was positive in normal ducts, ductal hyperplasia, dysplasia, and carcinoma cells in 0 of 14 (0%), 0 of 7(0%), 7 of 9 (78%), and 10 of 11 (91%), respectively, and K-ras was positive in 0 of 8 (0%), 1 of 3 (33%), 4 of 6 (67%), 4 of 5 (80%), respectively. CONCLUSION: Our results favorably support the hypothesis that ductal hyperplasia and dysplasia of the pancreas might be precursor lesions for pancreas cancer. Further evaluation of oncogenes by the molecular study is needed.     

Primary cancer of the small intestine and mutational analysis of the K-ras and p53 genes

A 69-year-old woman was admitted to Hokuso Shiroi Hospital because of recurrent pain in the lower right side of the abdomen. Small-intestinal cancer was strongly suspected after fluoroscopy of the small intestine. Laparotomy showed advanced cancer of the ileum, of complete annular constrictive type, 9.5 × 5 cm in size. Histologically it was moderately differentiated tubular adenocarcinoma. Neither visceral nor nodal metastases were found, and the patient has been well for the 20 months since surgery. The strong resemblance between the epidemiological characteristics of small-intestinal cancers and colorectal cancers prompted us to investigate the carcinogenetic mechanisms at the molecular level. A point mutation at codon 12 of the K-ras gene was found, while no alterations were noted in the p53 gene, whose mutations are frequent in colon cancers. The carcinogenetic mechanisms of the small-intestinal cancer we experienced may thus differ from those of colon cancers. (Received May 27, 1997; accepted Nov. 28, 1997)     

P53和PCNA蛋白在大肠癌中的表达及意义研究

目的研究P53蛋白和PCNA蛋白在肠癌中的表达及其生物学行为的关系。方法采用免疫组化技术（SP法）对50例肠癌组织进行P53和PCNA检测。结果 P53和PCNA阳性表达率分别为52.0%、76.0%,P53阳性表达率及PCNA强阳性表达率均与肠癌浸润深度、淋巴结转移密切相关,差异有统计学意义。结论 P53和PCNA蛋白可能与肠癌的浸润、转移及预后有关。     

大肠癌p53、K-ras基因突变研究

目的：探讨p53,K-ras基因突变与大肠癌发生、发展的关系。方法：应用PCR－SSCP方法研究68例大肠癌和癌旁组织以及20例正常组织p53,K-ras基因突变情况。结果：大肠癌组中p53，K-ras基因突变率分别为47．1％和44．1％，明显高于癌旁组（分别为13．2％和7．4％），20例正常组织中未检出p53、K-ras基因突变，大肠癌伴有淋巴结转移及远处转移，p53、K-ras基因突变率明显高于无淋巴结及远处转移；p53、K-ras基因突变与组织学分型无关。结论：p53、K-ras基因突变与大肠癌发生、发展有密切关系，在细胞癌变中起重要作用，可作为评估大肠癌转移的分子生物学指标。     

胃腺癌组织P53,P63和P73蛋白表达的意义

目的:探讨P53,P63和P73蛋白表达与胃腺癌临床病理特征之间的关系．方法:用免疫组织化学技术,检测72例胃腺癌及其癌旁正常组织中P53,P63和P73蛋白表达情况．所有研究对象均为湖北地区汉族人．其中,癌肿位于胃远端(胃窦、胃角)51例,胃近端(胃底、胃体)21例;肠型GAC 44例、弥漫型28例;高分化腺癌20例、中分化腺癌29例、低分化和未分化腺癌23例;TNM分期:Ⅰ和Ⅱ期13例,Ⅲ和Ⅳ期59例．结果:胃腺癌组织中P53,P63和P73蛋白阳性表达率均明显高于正常组织(X2=4．72,P<0．05; X2=5．51,P<0．05;X2=9．75,P<0．01);胃窦／胃角腺癌与胃底／胃体腺癌组织P53蛋白表达率无显著差异(P>0．05);在弥漫型胃腺癌中的表达率明显高于肠型胃腺癌(X2=4．68,P<0．05);在低分化腺癌与高中分化腺癌之间以及Ⅲ,Ⅳ期腺癌与Ⅰ,Ⅱ期胃腺癌之间的表达率的差异均有显著性(X2=7．06,P<0．05;X2=3．95, P<0．05)．P63蛋白在低分化腺癌组织中表达率明显高于高中分化腺癌(X2=7．36,P<0．05);在胃窦／胃角腺癌与胃底／胃体腺癌之间、在弥漫型与肠型胃腺癌之间、在Ⅰ,Ⅱ期胃腺癌与Ⅲ,Ⅳ期腺癌之间均无显著差异．P73蛋白在Ⅰ,Ⅱ期胃腺癌组织中的阳性表达率明显低于Ⅲ,Ⅳ期腺癌(X2=4．14,P<0．05),在胃窦／胃角腺癌与胃底／胃体腺癌之间、在弥漫型与肠型胃腺癌之间、在高、中及低分化胃腺癌之间均无显著差异．在P53蛋白阳性与阴性表达的胃腺癌之间,P63和P73蛋白阳性表达率的差异无显著性．结论:P53,P63和P73过度表达与胃腺癌的发生相关联,但并无交互作用．     

p53 expression,K-ras gene mutation and microsatellite instability in gastric B-cell lymphomas

BACKGROUND AND AIMS: Genetic mechanisms involved in the development of gastric B-cell lymphomas remain unclear. The aim of the present study was to clarify the roles of mutations of the p53 and K-ras genes, and microsatellite instability (MSI) in the development of gastric B-cell lymphomas. METHODS: We investigated p53 immunoreactivity, mutations of the K-ras gene, and MSI in 27 gastric marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue type (MZBCL) and 24 diffuse large B-cell lymphomas (DLBCL). p53 immunoreactivity was examined using a monoclonal antibody, DO-7. Mutation of the K-ras gene was detected by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis. MSI was examined at five microsatellite loci with a microsatellite assay. Cases were classified as having high-frequency MSI (MSI-H) (>/= 2 loci showing instability), low-frequency MSI (MSI-L) (only one locus showing instability), or as microsatellite stable. RESULTS: p53 immunoreactivity was detected in 1 of 16 (6%) MZBCL and 8 of 19 (42%) DLBCL. Frequency of p53 immunoreactivity in DLBCL was significantly higher than that in MZBCL (P = 0.018). MSI-H was detected only in 1 of 20 (5%) DLBCL. None of the cases examined showed mutation of the K-ras gene. CONCLUSIONS: These data suggest that mutations of the p53 gene may play an important role in the development of gastric DLBCL, and that mutations of the K-ras gene and MSI may be involved in little part of the development of gastric B-cell lymphomas.     

K-ras and p53 mutations in DNA extracted from colonic epithelial cells exfoliated in faeces of patients with colorectal cancer

BACKGROUND: Exfoliated colonic epithelial cells in faeces provide a source of human DNA which may be analysed for the presence of tumour-induced modification. AIM: In the present study we investigated K-ras and p53 mutations in faeces of patients with colorectal carcinoma, to verify whether analysis of these mutations might identify a high percentage of patients with colorectal cancer. PATIENTS AND METHODS: Faeces, tumour and normal mucosa samples were taken from 26 patients. Polymerase chain reaction amplification and restriction enzyme analysis were performed to detect K-ras mutations; p53 gene mutations were identified by using polymerase chain reaction amplification and single strand conformation polymorphism. RESULTS: We were able to amplify the K-ras gene and exons 5-9 of the p53 gene in 100% of the faecal samples studied. K-ras and p53 gene mutations were detected in faeces in 26.9% and 50% of the cases, respectively. The two mutations were present together in 5 out of 26 patients. There was full agreement between the K-ras and p53 pattern observed in faecal DNA and that in tumour tissue DNA. CONCLUSIONS: Application of K-ras and p53 mutation gene analysis in the faeces may have clinical applications in the future. Since this genetic analysis is able to detect only 57.7% of patients with colorectal cancer, the study of other genes involved in colorectal carcinogenesis is necessary.