EXPRESSION OF p16,CYCLIN D1 AND RB PROTEIN IN GASTRIC CARCINOMA AND PREMALIGNANT LESIONS

Gastric carcinoma is one of the most serious diseases in mankind. Its pathogenesis has not been understood very clearly. Recent researches suggested that oncogenes (such as cyclin D1), antioncogenes (ie., p16, Rb) and cell cycle played an important role in the pathogenesis of gastric carcinoma. But there are few reports about the relationship between these genes in gastric carcinoma and gastric premalignant lesions. In this study, we will discuss these problems. MATERIALS AND METHO…     

用组织芯片技术研究环氧合酶-2在不同亚型胃黏膜肠化生及胃癌中的表达

目的研究环氧合酶-2(cyclooxygenase-2,COX-2)蛋白在不同亚型胃黏膜肠化生(intestinal metaplasia,IM)及胃癌中的表达,探讨其做为预测IM恶变趋势指标的可能性,同时明确COX-2表达与胃癌发生间的关系。方法选择40例慢性萎缩性胃炎(chronic、atrophic gastritis,CAG)伴IM、40例胃癌及相应癌旁组织,构建组织芯片。分别用高铁二铵/爱先蓝(HID/AB)及HE染色对IM及胃癌进行分型,免疫组化检测不同亚型IM及胃癌中COX-2蛋白的表达。结果COX-2蛋白表达阳性率在CAG伴IM灶、癌旁IM灶和肠型胃癌中分别为45.65%、59.38%和77.27%,显著高于弥漫型胃癌(16.67%,P分别<0.05、0.005和0.005),表达强度在CAG伴IM灶→癌旁IM灶→肠型胃癌顺序中呈逐渐升高趋势(P<0.005)。Ⅲ型IM中COX-2表达阳性率显著高于Ⅰ型、Ⅱ型IM(P分别<0.005、0.05),从Ⅰ型、Ⅱ型到Ⅲ型,COX-2表达强度也呈逐渐升高趋势(P<0.005)。结论随着IM愈倾向于恶性,COX-2表达水平也逐渐增高,有可能成为预测IM恶变趋势的有用指标。COX-2表达主要与肠型胃癌的发生有关,但在弥漫型胃癌的发生中可能也有一定作用。     

Expression of p16, cyclin D<Subscript>1</Subscript> and RB protein in gastric carcinoma and premalignant lesions

Objective: To investigate the expression of p16, cyclin D₁ and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of p16, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D₁ protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D₁, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D₁ gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D₁ and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D₁ and Rb gene have some value to the diagnosis at earlier stage of gastric cancer. Detection of expression of p16, cyclin D₁ gene would be helpful to judge the prognosis of gastric cancer. Biography: MIAO Lin (1966–), male, master of medicine, associate professor, Second Affiliated Hospital, Nanjing Medical University, majors in gastroenterological cancer.     

Overexpression of p53 in different subtypes of intestinal metaplasia and gastric cancer.

p53 immunostaining was evaluated in cancerous epithelia and adjacent intestinal metaplasia of 135 gastric cancer specimens. The differential p53 overexpression in different subtypes of intestinal metaplasia and gastric cancer suggests that type III intestinal metaplasia is the commonest lesion in dysplasia-carcinoma transition, particularly in the intestinal type of gastric cancer.     

Ectopic expression of homeodomain protein CDX2 in intestinal metaplasia and carcinomas of the stomach.

The roles of CDX2 and CDX1 homeobox genes during gastric carcinogenesis remain poorly defined. We have studied the expression of CDX2/1 in gastric cancers and intestinal metaplasia (IM) of 69 gastric carcinoma patients by immunohistochemistry. CDX2/1 were shown to be ectopically overexpressed in IM in 41 (85%) of 48, and 47 (90%) of 52 cases, respectively. The expression of CDX2/1 was detected in 38 (55%) and 51 (74%) of the 69 gastric carcinomas, respectively. The histological type of the gastric carcinomas was independently associated with CDX2 expression, but not with that of CDX1, with higher CDX2 expression in intestinal type (differentiated type) than in diffuse type (undifferentiated type) gastric carcinomas. Our results thus suggest that CDX2 and CDX1 may play a role during IM formation and gastric carcinogenesis.     

肠特异性转录因子CDX2在不同亚型肠化生及胃癌组织中的表达

背景与目的：肠化生被认为是胃癌的癌前病变,而肠特异性转录因子CDX2在肠上皮的形成、分化及肠表型的维持方面有重要作用。近年来研究发现CDX2在慢性萎缩性胃炎（chronic atrophic gastritis,CAG）相关的肠化生中呈高水平表达,在部分胃癌组织中也有表达,提示其可能与胃粘膜上皮由胃表型向肠表型的转化,以及胃癌的发生有关。本研究旨在探讨CDX2在胃粘膜肠化生发生、进展及胃癌发生中的作用,进一步明确肠化生与胃癌发生的关系。方法：选择46例CAG伴肠化生、40例胃癌及32例对应癌旁肠化生,构建组织芯片。分别用高铁二铵／爱先蓝（HID／AB）及HE染色对肠化生及胃癌进行分型．然后用免疫组化和原位杂交检测不同亚型肠化生及胃癌中CDX2蛋白及mRNA的表达。结果：癌旁肠化生中Ⅲ型肠化生的比例显著高于CAG伴肠化生（分别为56．25％和21．74％,P〈0．01）。CDX2蛋白阳性率在CAG伴肠化生、癌旁肠化生和胃癌中分别为69.56％、53．13％和42．50％：CDX2 mRNA阳性牢分别为63．04％、46．87％和35．00％。胃癌中显著低于CAG伴肠化生（P〈0．01）,而与癌旁肠化生无显著性差异（P〉0．05）。CDX2表达与胃癌组织类型有关联,肠型胃癌显著高于弥漫型（P〈0．05）。Ⅲ型肠化生中CDX2蛋白表达显著低于Ⅰ型（P〈0．05）。结论：CDX2在胃粘膜肠化生发生及进展为胃癌过程中可能有重要作用。     

EB病毒相关胃癌与mdm2，p53及p21基因异常的研究

 目的 探讨p53基因突变以及mdm2，p53和p21蛋白表达异常在EBV相关胃癌（EBVaGC）发生发展中的作用。方法 应用免疫组化技术检测13例EBVaGC、45例临床病理资料与之匹配的EBV阴性胃癌（EBVnGC）组织中 mdm2，p53和p21蛋白的表达；PCR-SSCP银染技术结合DNA序列分析检测p53基因exon 5~8突变；RT-PCR检测EBV相关基因的表达。结果 E-BVaGC组与EBVnGC组相比，两组间mdm2，p53和p21蛋白的阳性检出率差异无统计学意义（P = 0.830 0；P = 0.791 2；P = 0.353 1），但EBVaGC组p53蛋白过表达率（15.38 %）明显低于EBVnGC组（57.78 %），两组间差异有统计学意义（P = 0.008 5）。mdm2蛋白阳性表达与p53蛋白过表达呈显著正相关（P = 0.000 8，r = 0.439 1）；p21与p53蛋白共同表达率较高，但经计数资料相关性统计学分析表明两者无显著相关性（P = 0.2501，r = 0.202 5）。2例EBVnGC检测到p53基因突变，突变均位于exon 5，13例E-BVaGC和58例相应癌旁组织均未检测到p53基因突变。13例EBVaGC核抗原基因EBNA1均为阳性，潜伏膜蛋白基因LMP1均为阴性，即刻早期基因BZLF1，早期基因BARF1和BHRF1阳性率分别为46.15 %（6／13），46.15 %（6／13）和15.38 %（2／13），三者与EBVaGC组织中mdm2，p21和p53蛋白的表达均无显著相关性（P＞0.05）。 结论 EBV感染以及mdm2，p53和p21蛋白表达异常与胃癌发生有关； p53基因突变可能并非胃癌组织中p53蛋白异常累积的主要原因；胃癌组织中EBV感染与p53蛋白的异常表达有关，而与mdm2和p21蛋白的异常表达以及p53基因突变无显著相关性。     

p53 polymorphism and p21WAF1/CIP1 haplotype in the intestinal gastric cancer and the precancerous lesions

The development of intestinal gastric carcinoma involves several precancerous stages. The environmental factor plays an important role in gastric carcinogenesis, while the host's genetic makeup may influence the susceptibility to cancer. In this study we investigated correlations of the p53 variations at codon 72 and p21(WAF1/CIP1) haplotype with the risk of intestinal gastric carcinoma. Forty-eight intestinal gastric carcinoma cases (GC), 96 chronic atrophic gastritis (CAG), 96 intestinal metaplasia (IM) and 96 dysplasia (DYS) controls were enrolled in this study. The p53 codon 72 proline allele carriers were found to be more susceptible to progress to GC than to IM (OR = 2.22, 95%CI = 1.05-4.70, P = 0.038). Patients carrying homozygous p21(WAF1/CIP1) haplotype A, which contains the serine at codon 31, the cytidine at the 16th base of the second intron, and the cytidine at the 70th base of the exon 3 were more prone to develop GC than to reach the IM or DYS stage (IM versus GC, OR = 3.35, 95%CI = 1.11-10.15; DYS versus GC, OR = 3.27, 95%CI = 1.09-9.80, P = 0.035). The combination of p53 codon 72 variation with the p21(WAF1/CIP1) haplotype further distinguished the risk of GC from IM precancerous lesion (OR = 9.31, 95% CI = 1.77-48.85, P = 0.08). These results suggest that p53 and/or p21(WAF1/CIP1) genotype may influence the progression during gastric tumorigenesis.     

p53和ras癌基因产物在胃癌及癌前病变中的表达

用LSAB免疫组比法，对20例胃癌、22例异型增生、30例肠化生及13例正常组织进行了ras－p21和突变型p53蛋白表达的检测．结果发现在ras－p21和突变型p53均阳性的胃癌组织分别为13例（65.0％）和12例（60．0％）；异型增生为12例（54．5％）和10例（45．4％）；肠化生11例（36．6％）和4例（13．3％），正常组织全部阴性。卡方检验结果，p值均小于0.05。胃癌、异型增生和肠化生三种组织中p21和p53联合表达分别为8例（40．0％）、7例（31．8％）和2例（6．7％）。提示ras原癌基因和p53抑癌基因突变是胃癌的早期事件，p21和p53可作为胃癌临床细胞学诊断的新指标。     

ING2和mP53蛋白在胃癌组织中的表达及临床病理意义

目的 检测生长抑制因子2(ING2)蛋白在正常胃组织、胃癌及其癌前病变组织中的表达,分析ING2与突变型P53(mP53)在胃癌中表达的关系,并探讨ING2与胃癌发生发展的关系及临床病理学意义.方法 免疫组织化学PV9000二步法检测188例胃癌及128例配对正常胃黏膜、35例慢性萎缩性胃炎、87例肠上皮化生及36例异型增生组织中ING2的表达.取其中的40例胃癌组织同时检测mP53蛋白的表达.结果 ING2蛋白在慢性萎缩性胃炎(74.29%)、肠上皮化生(91.95%)、异型增生(75.00%)和胃癌组织(70.21%)中阳性率均显著高于正常胃黏膜(36.72%),P＜0.001.ING2蛋白在胃癌中的表达与Lauren分型有关,在肠型胃癌中的表达率(80.56%)显著高于弥漫型(64.49%)和混合型胃癌(55.56%),P＜0.05,而且ING2蛋白在高-中分化管状腺癌的表达率(80.60%)显著高于低分化管状腺癌的阳性表达率(62.62%),P＜0.05.胃癌组织中ING2与mP53蛋白表达无相关性,P＞0.05.结论 ING2蛋白的过表达及细胞定位的改变可能参与胃癌的发生和分化,尤其是肠型胃癌的发生.     

Significance of Skp2 expression in human gastric carcinoma and the relationship between Skp2, p27 and PTEN expression

Objective： S-phase kinase-associated protein 2 （Skp2） is a positive regulator of G1-S transition and promotes ubiquitin-mediated proteolysis of the cyclin-dependent kinase inhibitor p27. Its overexpression has been implicated in cell transformation and oncogenesis. In this study, we investigated significance of Skp2 expression in human gastric carcinoma and the relationship between Skp2, p27 and PTEN expression. Methods： Immunohistochemical analysis was performed on 138 surgical resected primary gastric carcinoma specimens, 102 paired metastasis carcinoma tissue specimens in lymph node from the same set of 138 surgical resected primary gastric carcinoma specimens, 30 dysplasia specimens, 30 intestinal metaplasia specimens, and 20 normal gastric mucosa specimens for Skp2 and performed on the same set of 138 surgical resected primary gastric carcinoma specimens for p27 and PTEN. Results： Skp2 labeling frequency % was increased dramatically in intestinal metaplasia, dysplasia, and primary gastric carcinoma compared with normal gastric mucosa （P=0.000, all the same）. Skp2 labeling frequency % in metastasis gastric carcinoma in lymph node was significantly higher than primary gastric carcinoma （P=0.037）. Skp2 labeling frequency % was positively associated with differentiated degree （rho=0.315, P=0.000）, vessel invasion （rho=0.303, P=0.000） and lymph node metastasis （rho=0.254, P=0.000） respectively. An inverse correlation of Skp2 was observed with both its biochemical target p27 expression in gastric carcinoma （rho=-0.451, P=0.000） and with its putative negative regulator, the PTEN tumor suppressor protein （rho=-0.480, P=0.000）. p27 expression had positive relationship with PTEN expression in gastric carcinoma （rho=0.642, P=0.000）. Conclusion： Skp2 overexpression is correlated with carcinogenesis and progression of gastric carcinoma： elevated Skp2 expression is correlated with decreased p27 and PTEN in gastric carcinoma, and p27 expression is parallel with PTEN expression. These suggest that PTEN may regulate expression of p27 through the Skp2 pathway, and the effects of Skp2, p27 and PTEN together play an important role in carcinogenesis and progression of gastric carcinoma.     

Distribution of marker enzymes and mucin in intestinal metaplasia in human stomach and relation to complete and incomplete types of intestinal metaplasia to minute gastric carcinomas

Intestinal metaplasia of the human stomach was classified into two types, complete and incomplete. The complete type was associated with the intestinal marker enzymes sucrose alpha-D-glucohydrolase, alpha, alpha-trehalase, aminopeptidase (microsomal) (APM), and alkaline phosphatase (ALP). Tissue of this type contained goblet cells and Paneth's cells but not high-iron diamine (HID)-positive mucin staining with HID-Alcian blue. The incomplete type of intestinal metaplasia was associated with sucrose alpha-D-glucohydrolase, APM, goblet cells, and HID-positive mucin but not with alpha, alpha-trehalase, ALP, or Paneth's cells. For the examination of the distribution of the complete and incomplete types in 84, 27, and 16 resected specimens of human stomach with gastric carcinoma, gastric ulcer, and duodenal ulcer, respectively, disaccharidases were located with Tes-Tape. Specimens with intestinal metaplasia were divided into three classes: complete type only (class I), incomplete type only (class II), and a mixture of areas of the complete and incomplete types (class III). Of the 84 specimens from patients with gastric carcinoma, intestinal metaplasia was found in 76 (01%), and the percentages of specimens of classes I, II, and III were 32, 22, and 46, respectively. In these specimens, the percent incidence of class I increased and that of class II decreased with age. Of the 27 specimens from patients with gastric ulcer, 16 (59%) shopwed intestinal metaplasia and 10 of the 16 (63%) specimens were of class II. Of the 16 specimens from patients with duodenal ulcer, only 3 (19%) specimens showed intestinal metaplasia and all of them were of class II. The relationships of the complete and incomplete types of intestinal metaplasia to gastric carcinoma wre studied in 26 foci of minute carcinoma of the stomach less than 5 mm in largest diameter. Nineteen of 20 (05%) foci of the intestinal type of minute carcinoma were surrounded by intestinal metaplasia and 16 foci (80%) were surrounded by the incomplete type of intestinal metaplasia.     

Expression of CDX2 and villin in gastric cardiac intestinal metaplasia and the relation with gastric cardiac carcinogenesis

Objective: To determine whether CDX2 and villin protein expression are associated with intestinal metaplasia(IM) in gastric cardiac mucosa and to explore the relationship with evolution of gastric cardiac adenocarcinoma(GCA). Methods: We studied 143 gastric cardiac biopsy or resection specimens from Henan province China,including 25 cardiac gastritis specimens with IM, 65 dysplasia specimens with IM and 35 gastric cardiacadenocarcinoma specimens and stained them for CDX2 and villin by the immunohistochemical SP method.15 normal gastric cardiac biopsy specimens were also collected as control. Results: (1) Normal gastric mucosapresented no CDX2 and villin expression. The positive rates of CDX2 protein in cardiac gastritis with IM,dysplasia with IM, and carcinoma tissues were 84.0% (21/25), 66.7% (32/48) and 36.4% (20/55), respectively.While the positive rates of villin protein in cardiac gastritis with IM, dysplasia with IM, and carcinoma tissueswere 76.0% (19/25), 70.8% (34/48) and 45.5% (25/55), respectively.There were significant differences among thethree groups for both CDX2 and villin (P<0.01). Spearman’s rank correlation coefficient(rho) showed a closecorrelation between the two proteins (r=0.843, P<0.01) and both were positively related with tumor differentiation(both P<0.05), but not associated with age, sex, invasion and metastasis of lymph node (P>0.05). Conclusion: Ourresults suggest that ectopic expression of CDX2 and villin may be involved in early-stage IM and tumorigenesisin gastric cardia and the expression of villin may be regulated by CDX2.     

Is type III intestinal metaplasia an obligatory precancerous lesion in intestinal-type gastric carcinoma?

This retrospective study was performed to assess whether type III intestinal metaplasia is an obligatory precancerous lesion of intestinal-type gastric carcinoma and to determine its possible use as a marker of enhanced cancer risk. From 48 consecutive patients with gastric cancer who underwent a gastrectomy over a 3-year period (mean age 72.0 years; 29 M/19 F), at least two sections from antrum, corpus and tumour-surrounding mucosa were obtained for the examination of presence and subtypes of intestinal metaplasia (IM). It was found that 77.1% of the carcinomas were of the intestinal type and 22.9% of the diffuse type. The intestinal-type was more often found in males (P = 0.01); the mean age at diagnosis in this type was higher than in the diffuse cancer group (P = 0.004). There was a high prevalence of total IM in both the intestinal (75.7%) and diffuse group (88.9%). Type I IM was predominant in antrum and corpus of patients from both groups. Type III IM was only found among patients with intestinal-type carcinoma. However, its prevalence was rather low (26.3%). Therefore the absence of this lesion in patients with other risk factors cannot be used as an argument for lowering the degree of surveillance and its presence seems to be sufficient indication for long-term follow-up.     

幽门螺杆菌感染与不同胃粘膜病变中c-myc、Bcl-2和Bax表达的关系

背景与目的:幽门螺杆菌(Helicobacterpylori,HP)是确定的胃癌致癌因子之一,但其致癌的确切机制仍不清楚。本实验研究不同胃粘膜病变中幽门螺杆菌感染与细胞增生、凋亡的关系,探讨HP致胃癌发生的可能机制。方法:选择272例病例,包括慢性胃炎(chronicgastritis,CG)42例,肠上皮化生(intestinalmetaplasia,IM)Ⅰ～Ⅱ46例,IMⅢ25例,轻度不典型增生(dysplasiaⅠ,DysⅠ)21例,中、重度不典型增生(DysⅡ～Ⅲ)54例及胃癌(gastriccancer,GC)84例。采用Warthin-Starry细菌染色及SP免疫组化法检测HP的感染情况;HID-AB(pH2.5)-PAS粘液染色检测胃粘膜上皮及肿瘤组织中的粘液性质;SP法检测c-myc、Bcl-2和Bax的表达。采用卡方检验、Fishers精确概率法进行率的比较。结果:(1)在CG、IM、Dys、GC的胃粘膜病变标本中,c-myc、Bcl-2的表达率依次增加,而Bax的表达率则依次降低。c-myc在GC中的表达率显著高于DysⅡ～Ⅲ及IMⅢ(均P<0.01),而Bax在GC中的表达率明显低于DysⅡ～Ⅲ及IMⅢ(P<0.05或P<0.01)。(2)c-myc在IMⅢ、DysⅡ～Ⅲ病变的HP感染组中的表达率分别为62.50%、66.67%,明显高于非感染组的11.11%、27.78%(均P<0.05)。Bax在CG、IMⅠ～Ⅱ和IMⅢ病变的HP感染组中的表达率分别为87.10%、81.25%、62.50%,明显高于非感染组的54.55%     

O-acetyl sialomucin and differentiation of stomach cancer: a histochemical study

In one hundred surgical specimens with stomach cancer, 78 cases contained intestinal metaplasia (IM) in the outer margin mucosa nearby carcinoma focus, while the remaining 22 had no IM. IM was histochemically classified into small intestinal type, sulphomucin colonic type (S), O-acetyl sialo-sulphomucin colonic type (OS) and O-acetyl sialomucin colonic type (O). The incidence of OS and O in well differentiated carcinoma (WCa) (22/27) was obviously higher than in poorly and undifferentiated carcinomas (PUCa) (17/51) (X2 = 14.5011, P less than 0.001). This suggests that O-acetyl sialomucin in IM may be correlated with the differentiation of gastric cancer, that is, OS may often be transformed into WCa if malignant change of IM occurs.     

胃黏膜癌前病变和胃癌组织相关癌基因和抑癌基因表达差异的研究

目的:探讨胃黏膜癌前病变与胃癌组织中Bcl-2、Bax、p16和p53蛋白的表达和意义。方法:用免疫组化法检测Bcl-2、Bax、p16和p53产物在79例胃癌、23例胃黏膜不典型增生和21例肠上皮化生组织中的表达。结果:Bcl-2在胃癌和不典型增生组织中的阳性率分别为73.4%(58/79)和78.2%(18/23),差异无统计学意义,P=0.273;但是显著高于肠上皮化生组织(38.1%,8/21),P<0.01。Bax、p16和p53在胃癌和不典型增生及肠上皮化生组织中的阳性率分别为41.8%(31/79)、69.6%(18/23)、80.9%(17/21)和45.6%(36/79)、65.2%(15/23)、76.1%(16/21)及82.3%(65/79)、39.1%(9/23)、28.6%(6/21),差异有统计学意义,P<0.01。结论:Bcl-2对胃黏膜细胞凋亡有明显的负性调节作用,而抑癌基因Bax表达对Bcl-2的抑制凋亡功能有对抗调节作用;p16基因直接参与细胞生长增殖的负调节,突变的p53基因通过抑制细胞凋亡而参与胃癌的发生。     

胃癌及其有关病变的幽门螺杆菌感染与抑癌基因表达的相关性研究

背景与目的:幽门螺杆菌(Helicobacterpylori,Hp)是确定的胃癌致癌因子,但其致癌的确切机制仍不清楚。p53、p21WAF1、p16为主要的细胞周期负调控基因。本研究旨在探讨胃癌及其有关病变中,上述3种抑癌基因的作用及其与幽门螺杆菌感染的关系。方法:应用HID-AB(pH2.5)-PAS、SP免疫组化染色及Warthin-Starry染色,对65例慢性萎缩性胃炎(chronicatrophicgastritis,CAG),93例肠上皮化生(intestinalmetaplasia,IM),94例胃上皮不典型增生(gastricepithelialdysplasia,GED)及60例胃癌(gastriccarcinoma,GC)中3种抑癌基因表达和幽门螺杆菌感染情况进行检测。结果:在胃癌发生的不同阶段,p53阳性表达率随病变发展而升高,在CAG、IMⅠ～Ⅱ、IMⅢ、GEDⅠ级、GEDⅡ～Ⅲ级及GC中分别为0、1.64%、6.25%、5.45%、23.08%、70.00%。p21WAF1和p16阳性表达率随病变发展而降低,p21WAF1阳性表达率分别为100%、95.08%、100%、100%、71.79%、45.00%,p16阳性表达率分别为83.08%、81.97%、78.13%、89.09%、69.23%、40.00%。三者表达在GEDⅡ～Ⅲ与GEDⅠ组间、GC与GEDⅡ～Ⅲ组间的差异均具有显著性(P<0.05)。同一病变中,Hp感染阳性组p53、p21WAF1及p16阳性表达率虽然高于Hp阴性组,但差异无显著性(P>0.05)。结论:p53突变及p21WAF1、p16失活     

FXR和CDX2在胃黏膜肠化生及胃癌中的表达及意义

目的:探讨法尼酯衍生物X受体(farnesoid X receptor,FXR)和尾型同源盒2(caudal type homeobox 2,CDX2)在胃黏膜肠化生(intestinal metaplasia,IM)及胃癌中的表达和意义。方法:采用免疫组织化学染色法检测FXR和CDX2在30例慢性胃炎、50例IM、60例胃癌组织中的表达。利用卡方检验比较各组间FXR和CDX2的表达差异,并分析其与肠化生和胃癌患者临床病理参数的关系。利用Spearman秩相关检验分析FXR和CDX2表达的相关性。结果:IM和胃癌组织中FXR的高表达率分别为58.0%和38.3%,较慢性胃炎组织(13.3%)均显著增高（P＜0.05）。与IM组织相比,胃癌组织中FXR表达显著下降（P=0.040）。FXR高表达与IM患者肠化生程度较重（中重度）相关（P=0.025）。FXR高表达与胃癌患者分化较好（中高分化）相关（P=0.003）。IM和胃癌组织中CDX2的高表达率分别为46.0%和26.7%,较慢性胃炎组织(6.7%)均显著增高（P＜0.05）。与IM组织相比,胃癌组织中CDX2表达显著下降（P=0.035）。CDX2高表达与IM患者肠化生程度较重（中重度）相关（P=0.004）。CDX2高表达与胃癌患者分化较好（中高分化）相关（P<0.001）。FXR和CDX2表达在慢性胃炎、IM、胃癌组织中均显著正相关（P<0.001）。结论:FXR和CDX2在IM和胃癌组织中表达均上调且显著正相关,可能共同参与了IM和胃癌的发生发展。     

慢性胃病伴肠上皮化生、胃癌与幽门螺旋杆菌感染的关系

目的探讨慢性胃病伴肠上皮化生、胃癌与幽门螺旋杆菌（helicobacter pylore,HP）感染的关系。方法采用warthin—strarry银染色方法,对380例慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡组织及胃癌的癌旁组织进行HP检测．应用（alcianblue—PH2．5-periodic—schiff,AB—PAS）、（high-iron—diamine-alcianblue—PH2．5,HID-AB）黏液组织化学方法,区别慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡组织及胃癌的癌旁组织伴有肠上皮化生的类型。结果总例数380例。HP阳性率为69．74％。慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡组织及胃癌的癌旁组织伴肠上皮化生的HP感染率分别为77．78％、85．71％、100．00％、80．95％。慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡及胃癌的癌旁组织伴肠上皮化生AB—PAS染色阳性率分别为86．84％、91．43％、93．33％、100．00％;HID—AB染色阳性率分别为34．21％、42．86％、53．33％、85．71％。癌旁组织的肠上皮化生中,78．57％为不完全大肠型,慢性浅表性胃炎、慢性萎缩性胃炎、胃溃疡伴肠上皮化生中,不完全小肠型比例分别为52．63％、54．28％、53．33％;不完全大肠型比例分别为28．95％、31．43％、20．00％。结论HP感染与慢性胃病伴肠上皮化生及胃癌的发生密切相关。癌旁组织的不完全大肠型肠上皮化生与胃癌的发生密切相关;慢性胃病组织当中的小灶状不完全大肠型上皮化生具有潜在发生癌变的可能性。