环氧合酶-2在胃癌与癌前病变和其他胃黏膜组织中表达的研究

目的:研究胃癌与癌前病变和其他胃黏膜组织中环氧合酶-2(COX-2)的表达情况,探讨COX-2蛋白作为肿瘤分子标记物对胃癌和癌前病变进行辅助诊断的意义.方法:收集胃镜活检的正常胃黏膜、慢性浅表性胃炎、慢性萎缩性胃炎、胃黏膜肠化生、胃黏膜不典型性增生和胃癌组织,用免疫组织化学染色法检测COX-2蛋白在各种组织中的阳性表达情况.以正常胃黏膜组织和正常兔血清作阴性对照.结果:COX-2蛋白在胃癌前病变和和胃癌组织中的表达阳性率为48%-84%.胃癌和胃黏膜不典型性增生标本中COX-2蛋白表达阳性率显著高于正常胃黏膜、慢性浅表性胃炎、慢性萎缩性胃炎和胃黏膜肠上皮化生标本(P<0.05).而胃癌组织COX-2蛋白表达的阳性率与胃黏膜不典型性增生组之间无显著性差异(P>0.05).此外,慢性萎缩性胃炎和胃黏膜肠化生标本与正常胃黏膜和慢性浅表性胃炎标本之间COX-2蛋白表达阳性率亦有显著性差异(P<0.05);所有病变组的COX-2蛋白表达阳性率均比正常胃黏膜组显著性地升高 (P<0.05).结论:胃癌与癌前病变组织中COX-2蛋白的表达显著升高,COX-2蛋白可作为肿瘤标记物对胃癌和胃癌前病变进行辅助诊断.     

NF-κB在B细胞淋巴瘤组织中的表达及临床意义

目的 探讨核转录因子-κB（nuclear factor　κB,NF-κB）在B细胞淋巴瘤组织中的表达及其与临床病理特征的关系。方法 采用免疫组化法检测42例B细胞淋巴瘤组织（B细胞淋巴瘤组）及20例淋巴结反应性增生组织（对照组）中NF-κB蛋白的表达。分析NF-κB表达与B细胞淋巴瘤临床病理特征的关系。结果 NF-κB在B细胞淋巴瘤组织和淋巴结反应性增生组织中的阳性表达率分别为78.57%（33/42）和20%（4/20）,两组比较差异有统计学意义（P<0.001）。NF-κB的表达与恶性程度、临床分期有关（P<0.05）;而与年龄、性别、乳酸脱氢酶（LDH）水平无关（P>0.05）。结论 NF-κB在B细胞淋巴瘤发生、发展中起重要作用,有望成为判断淋巴瘤患者预后的指标。     

pERK在胃癌中的表达及临床意义

[目的]研究磷酸化细胞外信号调节激酶（pERK）在胃腺癌、慢性萎缩性胃炎及浅表性胃炎组织中的表达及意义。[方法]RT-PCR法检测胃腺癌、慢性萎缩性胃炎和浅表性胃炎新鲜组织中pERK mRNA表达;免疫组化法分别检测胃腺癌、慢性萎缩性胃炎和浅表性胃炎组织中pERK蛋白表达,并分析其蛋白表达与胃癌临床病理参数间的相关性。[结果]RT-PCR半定量结果显示,胃癌组织中pERK mRNA的相对表达水平（2.35±0.36）明显高于慢性萎缩性胃炎组织（1.18±0.25）及浅表性胃炎组织（0.68±0.10）（P均〈0.01）。免疫组织化学结果显示,pERK蛋白在胃癌组织中的阳性表达率（88.3%）高于慢性萎缩性胃炎（43.3%）及浅表性胃炎组织（5.0%）（P均〈0.01）。胃癌组织中pERK蛋白表达与胃癌分化程度、分期、淋巴结转移等明显相关。[结论]pERK在胃癌中高表达,pERK在正常细胞向恶性细胞转化的过程中可能扮演了重要角色,检测pERK表达可能有助于胃腺癌的预防及早期诊断。     

S100 A6蛋白在胃癌组织中的表达及生物学意义

目的：探讨钙结合蛋白S100A6在胃癌组织中的表达及生物学意义。方法：用组织微阵列技术构建包含51例胃癌、15例慢性萎缩性胃炎、15例正常胃黏膜组织的81点阵的石蜡组织芯片。免疫组化SP 法检测该芯片中S100A6蛋白的表达并测定其灰度值,分析其与胃癌的关系。结果：51例胃癌组织中,S100A6蛋白阳性表达率为80．4％（41／51）,平均灰度值为125．84±13．05;15例正常胃黏膜组织中未见表达;15例慢性萎缩性胃炎中阳性率为20．0％（3／15）,平均灰度值为115．86±3．00。胃癌组与正常胃黏膜组比较,P ＝0．001;胃癌组与慢性萎缩性胃炎组比较,P＝0．049;正常胃黏膜组与慢性萎缩性胃炎组比较,P＝0．14。S100A6蛋白的表达与年龄、性别及肿瘤组织分级、分期无明显关系。结论：S100A6蛋白与胃癌相关,可能与胃癌的发生及发展有密切关系。     

陕北胃癌高发区胃黏膜组织中MAD2的表达及意义

目的：研究MAD2在正常胃黏膜、胃病变黏膜组织中的表达,并探讨其与浅表性胃炎、萎缩性胃炎、不典型增生、胃癌之间的关系。方法：应用免疫组织化学sP法检测219例不同胃组织标本中MAD2的表达情况,所有标本均经病理证实。结果：MAD2在正常胃黏膜、浅表性胃炎、萎缩性胃炎、不典型增生、胃癌黏膜组织中的阳性表达率随病理学分类的不同而有差异。其中不典型增生、胃癌黏膜组织中MAD2的阳性表达率与其余各组MAD2的阳性表达率有明显的差异（P〈0．05）。结论：胃病变组织中MAD2蛋白的异常高表达,对诊断不典型增生、胃癌有重要的参考意义。     

syndecan-1在胃黏膜癌变不同阶段组织中的表达及意义

目的探讨黏附分子syndecan-1在胃癌癌变各阶段的表达及其在胃癌发生和转移中的意义。方法选取56例慢性浅表性胃炎、50例慢性萎缩性胃炎、59例肠化生、61例中重度异型增生、55例无淋巴结转移胃癌、57例有淋巴结转移胃癌的病理组织蜡块,采用免疫组化ABC法检测syndecan-1在胃黏膜癌变各阶段组织中的表达。结果慢性浅表性胃炎组、慢性萎缩性胃炎组、肠化生组、中重度异型增生组、无淋巴结转移胃癌组、有淋巴结转移胃癌组syndecan-1阳性表达率分别为96.43%、98.00%、100.00%、91.80%、45.45%和24.56%。慢性浅表性胃炎组、慢性萎缩性胃炎组、肠化生组3组间差异无统计学意义(P>0.05);肠化生组与中重度异型增生组、中重度异型增生组与无淋巴结转移胃癌组、无淋巴结转移胃癌组与有淋巴结转移胃癌组之间差异均有统计学意义(P均< 0.05)。低分化胃癌组syndecan-1阳性表达率为24.62%,明显低于中、高分化胃癌组(42.55%)。结论黏附分子syndecan-1表达下调与胃癌的发生有关,并可能进一步促进胃癌转移。     

Leptin、NF-κBp65在子宫颈上皮内病变组织中的表达及意义

目的 探讨瘦素（leptin）、核转录因子-κBp65（nuclear factor κBp65,NF-κBp65）与子宫颈上皮内瘤变（cervical inraepithelial neoplasia,CIN）发生、发展的关系。方法 采用免疫组化染色MaxVisionTM法检测63例慢性子宫颈炎（炎症组）、125例CIN组织（CIN组）中Leptin 和NF-κBp65的表达。结果 Leptin在炎症组中100%表达,且呈强阳性表达,在CIN组中随着CIN级别的升高其表达逐渐减弱;NF-κBp65在炎症组和CIN组织中阳性表达率均为100%,CIN组为强阳性表达,其表达强度随CIN 级别升高而增强,差异有统计学意义（P＜0.05）。Leptin和NF-κBp65的表达强度呈负相关（r =-0.234 ,P＜0.05）。结论 NF-κBp65的高表达对CIN的发生、发展起促进作用。在CIN发生、发展过程中,可能由于细胞异常增生影响Leptin合成与分泌而致其表达下降或异常。     

DEK在胃癌组织中的表达及意义

目的 通过检测DEK基因在胃正常黏膜、慢性萎缩性胃炎及胃癌组织中的表达,探讨其在胃癌发病机制中的作用及意义。方法 收集2008年1月至2011年2月昆明医学院第二附属医院和第四军医大学西京医院病理科保存的病理组织石蜡切片,采用免疫组化SP法检测DEK在49例胃正常黏膜、63例慢性萎缩性胃炎及132例胃癌组织中的表达并分析其临床意义。结果 在132例胃癌组织中DEK基因的阳性表达率为78.0％（103／132）,明显高于慢性萎缩性胃炎组织的60.3％（38／63）和正常胃黏膜组织的28.6％（14／49）,差异有统计学意义（P＜0.05）。DEK表达与胃癌组织的分化程度及有无淋巴转移有关（P＜0.05）,但与性别、年龄、肿瘤大小、侵犯深度及TNM分期均无关（P＞0.05）。结论 随着慢性萎缩性胃炎的进展,DEK基因逐步激活,在胃癌组织中出现DEK基因大量激活;DEK基因激活与胃癌发生有关,且与胃癌的组织分化程度和肿瘤转移有一定关系。     

胃癌及癌前病变细胞凋亡与Caspase-9，Bax表达的关系

目的：探讨细胞凋亡基因Caspase-9和Bax在胃癌前病变和胃癌发展中的作用。方法：应用免疫组化S—P法检测Caspase-9和Bax在57例胃癌及48例非癌胃黏膜组织的表达,用原位末端标记法（TUNEL法）检测相应胃组织细胞凋亡。结果：Caspase-9蛋白在非癌胃黏膜组（慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、不典型增生）阳性表达率分别为100．00％、86．67％、50．00％、42．85％,呈逐渐下降趋势。慢性浅表性胃炎组中Caspase-9蛋白阳性表达率与肠上皮化生、不典型性增生有显著性差异（P〈0．05）,肠上皮化生组Caspase-9蛋白阳性表达率高于不典型增生组,但无统计学差异（P〉0．05）。Bax蛋白在48例非癌胃组织中的阳性表达率分别为：慢性浅表性胃炎100．00％、慢性萎缩性胃炎80．00％、肠上皮化生56．25％、不典型增生57．14％,呈逐渐下降趋势,其中慢性浅表性胃炎组Bax蛋白阳性表达率与肠上皮化生、不典型增生有显著性差异（P〈0．05）。慢性浅表性胃炎、慢性萎缩性胃炎、肠匕皮化生、不典型增生、胃癌组织中,AI值（细胞凋亡指数）分别为（14．72±2．68）％、（10．02±2．34）％、（7．55±2．80）％、（6．09±2．35）％、（3．26±1．23）％,呈逐渐下降趋势,有显著性差异（P〈0．05）。结论：Caspase-9和Bax可能参与胃癌癌前病变的形成,促进胃癌的发生。     

陕北胃癌高发区胃黏膜组织中MAD2的表达及意义

目的:研究MAD2在正常胃黏膜、胃病变黏膜组织中的表达,并探讨其与浅表性胃炎、萎缩性胃炎、不典型增生、胃癌之间的关系.方法: 应用免疫组织化学SP法检测219例不同胃组织标本中MAD2的表达情况,所有标本均经病理证实. 结果: MAD2在正常胃黏膜、浅表性胃炎、萎缩性胃炎、不典型增生、胃癌黏膜组织中的阳性表达率随病理学分类的不同而有差异.其中不典型增生、胃癌黏膜组织中MAD2的阳性表达率与其余各组MAD2的阳性表达率有明显的差异(P<0.05).结论: 胃病变组织中MAD2蛋白的异常高表达,对诊断不典型增生、胃癌有重要的参考意义.     

Hand‐Schüller‐Christian Disease and Erdheim‐Chester Disease: Coexistence and Discrepancy

Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD) share similar clinical features and mechanisms. In very rare circumstances, the two diseases coexist in the same patient. Here we report such a patient, who was first diagnosed with Hand-Schüller-Christian disease (HSC), a type of LCH. Several years later, the patient presented with severe exophthalmos and osteosclerosis on radiograph. New biopsy revealed ECD. We also analyze 54 cases of LCH and 6 cases of ECD diagnosed in our hospital, as well as their progression during a follow-up period of 8 years. In five cases of HSC (9.3% of LCH), a triad of central diabetes insipidus, hyperprolactinemia, and pituitary stalk thickening on magnetic resonance imaging (MRI) preceded the typical bone lesions by 4–9 years. In addition, LCH was featured as elevated plasma alkaline phosphatase (ALP), which was normal in ECD. Combined with a literature review, several features are summarized to differentiate ECD from HSC. In patients with diabetes insipidus, concomitant hyperprolactinemia and pituitary stalk thickening on MRI indicate a possible HSC. Additionally, if osteosclerosis is observed in a patient with LCH, the coexistence of ECD should be considered.     

The Biology of <Emphasis Type="Italic">K-Ras</Emphasis> and <Emphasis Type="Italic">B-Raf</Emphasis> Mutations in Colorectal Cancer

Ras and Raf proteins are two major players in the MAP kinase pathway. They are crucial downstream regulators of multiple receptor tyrosine kinase-mediated cell growth, transformation, and maintenance of the malignant phenotype in human cancers. Mutations have been identified in K-Ras and B-Raf in patients with colorectal cancer. Clinical studies in colorectal cancers demonstrate that the therapeutic efficacy of cetuximab, a chimeric monoclonal antibody against epidermal growth factor receptor, depends on the presence of wild-type K-Ras. However, mutations in B-Raf do not predict cetuximab resistance. These observations have led to the use of K-Ras as a predictive biomarker, allowing clinicians to direct the therapy of cancer patients based on their K-Ras mutational status.     

High resolution melting analysis for rapid and sensitive <Emphasis Type="Italic">EGFR</Emphasis> and <Emphasis Type="Italic">KRAS</Emphasis> mutation detection in formalin fixed paraffin embedded biopsies

Background  

Epithelial growth factor receptor (EGFR) and KRAS mutation status have been reported as predictive markers of tumour response to EGFR inhibitors. High resolution melting (HRM) analysis is an attractive screening method for the detection of both known and unknown mutations as it is rapid to set up and inexpensive to operate. However, up to now it has not been fully validated for clinical samples when formalin-fixed paraffin-embedded (FFPE) sections are the only material available for analysis as is often the case.     

Metabolic assessment of monofocal acute inflammatory demyelination using MR spectroscopy and <Superscript>11</Superscript>C-methionine-, <Superscript>11</Superscript>C-choline-, and <Superscript>18</Superscript>F-fluorodeoxyglucose-PET

Monofocal acute inflammatory demyelination (MAID), which is observable by CT and MRI as a well-enhanced mass lesion with prominent perifocal edema, is very similar to malignant gliomas radiologically, making differential diagnosis of the two pathologies difficult. The aim of this study was to assess the different metabolic activities between MAID and malignant gliomas by MRS, methionine-PET, choline-PET, and FDG-PET. Six patients with MAID underwent methionine, choline, and FDG-PET, and 4 of the patients also underwent magnetic resonance spectroscopy (MRS). The images obtained from these patients were compared with the corresponding images of 19 anaplastic astrocytomas (AA) and 21 glioblastomas (GBM). The mean choline/creatine ratio of MAID was significantly lower than that of GBM. There were no significant differences in the mean NAA/creatine and lactate/creatine ratios among these pathologies. The methionine T/N ratio of MAID was significantly lower than those of AA and GBM. The choline T/N ratio of MAID was significantly lower than that of GBM. There were no significant differences in the FDG T/N ratios among these pathologies. These results demonstrate that the metabolic activity of MAID significantly differs in part from that of malignant gliomas. Combined PET and MRS neuroimaging examinations may be useful for differential diagnosis of these pathologies.     

ABO blood type, <Emphasis Type="Italic">Lewis </Emphasis>and <Emphasis Type="Italic">Secretor </Emphasis>genotypes,and chronic atrophic gastritis: a cross-sectional study in Japan

Background: The H type I structure, synthesized by the secretor (Se) enzyme in gastric foveolar cells, and its metabolite, Lewis b (Le ^b ) antigen, mediate the adhesion of Helicobacter pylori ( H. pylori ) to the gastric epithelium, whereas H. pylori does not bind to modified forms of Le ^b specific for blood types A and B. Such host factors as Le and Se genotypes and ABO blood type may affect the establishment of H. pylori infection and, once infected, the risk of chronic atrophic gastritis. Methods: We investigated the cross-sectional relation of ABO blood type and Le and Se genotypes to gastric atrophy, assessed by serum pepsinogen levels, in Japanese residents from two sources. Results: Among the 151 H. pylori -positive participants of the H. pylori eradication program, odds ratios (ORs) for gastric atrophy, adjusted for age, sex, and smoking, were elevated for blood types A (OR = 5.35; 95% confidence interval (CI), 2.11–13.58) and B (OR = 4.79; 95% CI, 1.77–12.93) relative to type O. ORs for blood types A and B were also elevated in H. pylori -negative subjects. These associations were not observed among 250 H. pylori -positive health check-up examinees. The Le genotype was not associated with gastric atrophy in either study population. The se / se genotype was associated with statistically nonsignificant elevation of gastric atrophy risk in both populations. Conclusions: The present data showed a strong association of blood types A and B with gastric atrophy in one, but not the other, study population. Discrepant results between the two populations warrant further investigation. Received: July 29, 2002 / Accepted: September 17, 2002 Acknowledgments The authors thank Dr. Hidemi Ito, Ms. Michiyo Tani, Ms. Naomi Takeuchi, and Ms. Mayumi Kato for their assistance in laboratory assays. This work was supported in part by a Grant-in-Aid for the Second Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labor, and Welfare, Japan, and grant R01CA73011 from the National Cancer Institute, the National Institutes of Health, USA. Offprint requests to: N. Hamajima