胃癌神经内分泌分化的免疫组化及超微结构观察

目的观察胃癌神经内分泌（NE）分化的CgA、Syn、NSE免疫组化表达及超微结构形态。方法对168例手术切除石蜡包埋胃癌标本进行CgA、Syn、NSE免疫组化标记,阳性病例分别进行电镜检查。对CgA、Syn、NSE免疫组化在胃癌神经内分泌分化中的诊断价值进行了讨论。结果80例NE标记阳性标本中,电镜下发现NE颗粒39例,检出率为48.8%。Syn^＋组灵敏度最高,为66.7%;最低的是Syn、CgA、NSE均阳性组,为15.4%。在所有的标记中特异度最高为Syn、CgA、NSE均阳性组,其特异度为97.6%。NSE^＋组的特异度最低,为24.4%。约登指数排在最前的为CgA^＋组（0.495）,最后的为NSE^＋组（-0.271）。结论电镜下发现NE颗粒可确定胃癌神经内分泌分化的诊断,免疫组化CgA、Syn阳性可协助诊断。     

子宫内膜样腺癌组织中CgA、NSE、Syn、ER、PR表达及意义

目的观察子宫内膜样腺癌（EC）组织中嗜铬素A（CgA）、神经特异性烯醇化酶（NSE）、突触素（Syn）及雌激素受体（ER）、孕激素受体（PR）的表达变化,并探讨其意义。方法采用免疫组化法检测60例EC组织（观察组）及40例同期因子宫肌瘤行子宫全切的内膜组织（对照组）中的CgA、Syn、NSE、ER、PR。结果观察组CgA、NSE阳性率均高于对照组,P均〈0.05。观察组中,高中分化组织CgA、NSE、ER、PR阳性率均高于低分化组织,P均〈0.05;浸润深度〈1/2组织ER、PR阳性率均高于浸润深度≥1/2组织,P均〈0.05。EC组织中,CgA与ER、NSE与PR表达均呈正相关（r=0.381、0.453,P均〈0.05）。结论 EC组织中CgA、Syn表达升高,CgA、Syn、NSE等神经内分泌因子有助于EC的病情判断。     

胃癌组织中神经内分泌细胞的临床病理意义

目的探讨胃癌中神经内分泌(NE)细胞的生物学及临床病理意义。方法应用光镜、组化、免疫组化、透射电镜对189例各组织学类型胃癌的 NE 细胞进行观察,并对其中127例患者进行随访。85例检出 CgA 阳性癌细胞(45.0%)。其中73例进一步做各类激素抗体检测。结果所采用的9种激素抗体在胃癌组织中均有阳性表达。85例检出 CgA 阳性癌细胞,其中49例表达2种及以上激素。NE阳性癌细胞多出现在分化差的胃癌组织学类型中(P<0.01)。某些激素种类的表达与胃癌组织学类型及分化关系较密切。BOM、CT(P<0.01),GSAT、5.HT(P<0.05)多存在于分化差的癌中。不同的 NE 细胞其 NE 颗粒形态不同。NE 阳性胃癌组40例的淋巴结转移癌灶中19例有转移 NE 阳性细胞,其中13例 HCG 表达阳性(68.4%),明显高于其他激素的阳性表达(P<0.01)。NE 细胞阳性胃癌患者组存活率为38.9%;阴性组52.7%。4例 HCG 阳性胃癌患者随访12—29个月全部死亡,而7例生长抑素阳性胃癌患者随访33-66个月还有5例存活。结论胃癌中某些 NE 细胞在分化差的癌中检出率较多,不同种类的激素对胃癌侵润转移及预后可能有不同的影响。     

肺活检诊断肺小细胞癌9例临床病理观察

目的探讨肺小细胞癌的临床病理特点。方法回顾性分析9例肺小细胞癌的临床病理资料和免疫组化标记的表达情况。结果肺小细胞癌占同期肺癌总数的14.8%,平均年龄63.5岁。表达神经内分泌标记NSE、CgA、Syn,CD56;淋巴细胞标记LCA阴性。结论肺小细胞癌具有恶性程度高、进展迅速、神经内分泌源性抗体标记阳性等特点。     

非小细胞肺癌神经内分泌表达的检测及其临床意义

目的 为研究非小细胞肺癌的神经内分泌分化状况及其对化疗疗效的影响。方法 应用Western印迹法和免疫组织化学方法分别检测了42例非小细胞肺癌（鳞癌18例、腺癌17例、大细胞癌4例、肺泡细胞癌3例）组织中神经特异性烯醇化酶（NSE）、嗜铬粒素A（CgA）和突触素（SYN）的表达,并有电镜观察了上述病例的神经内分泌颗粒的超微结构。对35位患者进行了化疗反应的观察。结果 （1）Western印迹法在非小细胞肺癌（NSCLC）中检测NSE、CgA和SYN的阳性率分离66．9％、19．0％和33．3％,均高于免疫组化的45．2％、9．5％和26．2％。（2）Western印迹法和免疫组化的检测结果与肺癌的组织类型和分化程度无明显关系。（3）化疗有反应组的3种标记物在免疫组化和Western印迹检测中阳性离均高于化疗无反应组（P＜0．05）。结论 NSCLC中存在较高比例的神经内分泌分化,其中NSE阳性率最高,SYN次之,CgA的检出率则较低。Western印迹法和免疫组化对非小细胞肺癌中神经内分泌成分的诊断均有重要帮助,以Western印迹法更为敏感。神经内分泌分化可能是影响NSCIL对化疗反应的重要因素之一。     

胃腺癌组织中Snail、E-cadherin蛋白的表达变化及意义

目的观察胃腺癌组织中Snail、E-cadherin蛋白的表达变化,并探讨其意义。方法采用免疫组化SP法检测112例胃腺癌患者肿瘤组织和79例癌旁组织中的Snail、E-cadherin蛋白。结果胃腺癌组织中Snail阳性92例（82.1%）,E-cadherin阳性38例（33.9%）,癌旁组织中分别为28例（35.4%）、79例（100%）,胃腺癌组织中Snail、E-cadherin蛋白阳性表达率相比P均〈0.05。胃腺癌组织中Snail的表达与肿瘤浸润深度、分化类型、是否有淋巴结转移以及远处转移相关（P均〈0.05）。E-cadherin的表达与肿瘤浸润深度、分化类型、是否有淋巴结转移、远处转移以及临床分期相关（P均〈0.05）。Snail蛋白和E-cadherin蛋白在胃腺癌组织中的表达呈明显负相关（r=-0.212,P〈0.05）。结论胃腺癌组织中Snail蛋白表达上调,E-cadherin蛋白表达下调。联合检测Snail、E-cadherin蛋白可以作为预测胃癌恶性程度的指标     

嗜铬素A和突触素对胃肠胰腺神经内分泌肿瘤诊断及预后的临床价值

目的 探讨胃肠胰腺神经内分泌肿瘤(GEP-NET)组织中嗜铬素A(CgA)和突触素( Syn)的表达及临床意义.方法 收集2003年1月至2009年5月南京医科大学第一附属医院收治的66例GEP-NET患者.免疫组织化学法分析CgA、Syn在GEP-NET组织中的表达情况及其与GEP-NET临床病理特征、预后间的关系.结果 66例患者中Syn的阳性率为87.9％(58/66),高于CgA[71.3％ (47/66),x2=5.63,P=0.02].64.6％(42/66)的患者同时表达CgA和Syn.GEP-NET组织中CgA的表达与肿瘤淋巴结转移及TNM分期有关,但与患者性别、年龄、发病部位、功能状态、分化程度、肿瘤大小、浸润范围及远处转移均无关.Syn与上述所有参数均无关.CgA阴性组3年生存率为47％,明显低于阳性组(78％,x2=0.00,P=0.01).结论 Syn诊断GEP-NET的敏感度高于CgA,CgA对GEP-NET预后判断有一定的指导意义.     

消化道混合性腺神经内分泌癌9例病理形态观察

目的分析消化道混合性腺神经内分泌癌的病理形态特征,探讨其诊断要点。方法对确诊为混合性腺神经内分泌癌的消化道手术切除标本9例进行光镜观察和突触素(Syn)、嗜铬粒蛋白(CgA)、癌胚抗原(CEA),细胞角蛋白8/18(CK8/18),Ki-67等5种抗体免疫组织化学染色,并复习其临床资料.结果镜下可见具有腺癌特征和神经内分泌肿瘤特征的两种区域,各种标志物的免疫组化染色阳性比率:CEA及CK8/18全部阳性(9/9,100%),Syn阳性6例(6/9,66.7%),CgA阳性5例(5/9,55.6%)。结论消化道混合性腺神经内分泌癌临床上比较少见,形态学上与常见的低分化腺癌不易区分,需要依靠免疫组化检测进行区分,其预后较一般腺癌差。     

胃癌组织中环氧合酶-2与基质金属蛋白酶的表达及与胃癌生物学特征的关系

目的 探讨胃癌组织中环氧合酶-2 （COX-2）与基质金属蛋白酶-2（MMP-2）的表达及其与胃癌生物学特征的关系.方法 采用免疫组化方法检测90例胃癌原发灶标本中COX-2和MMP-2的表达,并观察其与胃癌生物学特征的关系以及COX-2与MMP-2表达的相关性.结果 90例胃癌组织中,COX-2和MMP-2的表达阳性率分别为74.4%（62/90）和68.9%（62/90）;COX-2的表达与胃癌临床分期、组织分化程度、有无淋巴结转移及TNM分期呈明显相关（P＜0.05）,而与年龄、性别和发病部位无关;MMP-2的表达与胃癌临床分期、有无淋巴结转移及TNM分期亦呈明显相关（P＜0.05）,但与组织分化程度无明显相关（P＞0.05）;且COX-2的表达与MMP-2的表达存在明显相关性（P＜0.01）.结论 胃癌组织中COX-2的表达与MMP-2的表达密切相关,COX-2可能通过上调MMP-2的表达来促进肿瘤的浸润与转移.     

91例胃癌患者真核细胞起始因子与血管内皮生长因子的表达及其临床意义

目的探讨胃癌中真核细胞起始因子4E（eIF4E）和血管内皮生长因子（VEGF）的表达情况、相互关系及其临床意义.方法应用免疫组化的方法检测91例胃癌及30例正常胃组织中eIF4E及VGEF的表达水平.结果在正常胃组织中未见eIF4E或VEGF阳性表达,在胃癌组织中eIF4E及VEGF的阳性表达率分别为95.6%（87/91）和68.1%（62/91）.eIF4E及VEGF表达与胃癌浸润深度、淋巴结转移以及临床分期有关（P＜0.05）,但与肿瘤组织学分化程度、年龄、性别无关.胃癌中eIF4E与VEGF表达密切相关（P＜0.05,r=0.407）.结论胃癌组织中eIF4E和VEGF表达水平异常增高在胃癌的发生发展过程中起重要作用,可作为评价胃癌生物学行为的参考指标之一.     

Mixed adenoneuroendocrine carcinoma of the ampulla:Two case reports

Mixed adenoneuroendocrine carcinoma(MANEC)is a malignant tumor with adenocarcinoma and neuroendocrine components,with≥30%of each component required.MANEC of the ampulla is rare.To the best of our knowledge,only 15 cases of MANEC of the ampulla have been reported in the English-language literature.Here,we report two cases of MANEC of the ampulla in two womenaged 43 and 60 years,which was confirmed by histology after pancreaticoduodenectomy.These tumors contained neuroendocrine and adenocarcinoma components.The neuroendocrine components were positive for chromogranin A(Cg A),synaptophysin(Syn)and CD56 by immunostaining.The adenocarcinoma components were negative for Cg A,Syn and CD56.Both cases were T3N0M0(StageⅢA).They survived for 15 and 20 mo after surgery,respectively.A brief discussion about the histopathological features,clinical behavior and treatment of MANEC of ampulla,and review of the relevant literature are presented.     

非小细胞肺癌多药耐药及其与神经内分泌分化的相关性研究

目的　检测非小细胞肺癌 (NSCLC)多药耐药 (MDR)有关蛋白的表达 ,探讨其与神经内分泌 (NE)分化的关系。方法　采用链霉亲和素 过氧化酶连接 (SP)免疫组化法检测 113例NSCLC中谷胱甘肽S转移酶π(GST π)、多药耐药相关蛋白 (MRP)、肺耐药相关蛋白 (LRP)、神经元特异性烯醇化酶 (NSE)、突触素 (SYN)和嗜铬素A(CgA)的表达。结果　 (1)NSCLC中MRP和LRP的表达与组织学类型有关 (P <0 0 5 )。GST π与MRP、MRP与LRP表达之间呈显著相关 (P <0 0 5 )。 (2 )NSCLC中NSE、SYN、CgA的阳性率分别为 5 3 1%、2 6 6%、6 2 %。至少有 2种NE标记物表达者有 2 4例 (2 1 2 % ) ,其表达与肿瘤的分化程度有关 (P <0 0 5 )。 (3 ) 3种MDR有关蛋白在至少有 2种NE标记物阳性组的表达均较阴性组为低 (P <0 0 5 )。结论　GST π、MRP和LRP的过表达是NSCLC产生原发性多药耐药的重要原因。NE分化可能是影响多药耐药有关蛋白表达的因素之一     

Expression of mucins and E-cadherin in gastric carcinoma and their clinical significance

AIM: To investigate the expression of three types of mucin(MUC1, MUC2, MUC5AC) and E-cadherin in human gastric carcinomas and their clinical significance. METHODS: Ninety-four gastric cancer specimens were classified according to WHO criteria and detected by immunohistochemical assay of expression of mucins and E-cadherin. RESULTS: The positive expression rates of MUC1, MUC2, MUC5AC and E-cadherin were 82% (77/94), 84% (79/94), 40% (38/94) and 56% (53/94) respectively. MUC1 expression was significantly correlated with the types of cancer (the positive rates of MUC1 in well and moderately differentiated tubular adenocardnoma, poorly differentiated adenocardnoma, signet-ring cell carcinoma and mucinous carcinoma were 91%, 87%, 71%, 71%, respectively, P&lt;0.05), age of patients (the positive rates of it among the people who are younger than 40 years, between 40-60 years and over 60 yearwere 74%, 81%, 89%, P&lt;0.05), lymph nodes involvement (the positive rates in the non-interfered group and the interfered group were 78%, 85%, P&lt;0.05) and tumor size (the positive rates in the tumors with the size less than 3 cm, 3-6 cm and larger than 6 cm were 69%, 92%, 69%, P&lt;0.05); MUC2 expression was significantly associated with types of cancers and had the strongest expression in mucinous carcinomas (the posrdve rates of MUC2 in well and moderately differentiated tubular adenocardnoma, poorly differentiated adenocardnoma,signet-ring cell carcinoma and mucinous carcinoma were 94%, 70%, 81%, 100%, P&lt;0.05), but it had no obvious relation to age, gender, tumor location, lymph nodes involvement,depth of invasion and metastasis to extra-gastric organs (P&gt;0.05); MUC5AC expression was not related to any of the characteristics investigated except that it had relation to gender, whereas MUC5AC showed the tendency to higher expression in less invasive lesions and lower expression in advanced stage cancers (P&gt;0.05); No significant difference was found for E-cadherin expression. There were strong positive relationships between the expression of MUC1 and E-cadherin, MUC2 and E-cadherin, MUC1 and MUC2(R=0.33, R=0.22, R=0.32, respectively, P&lt;0.05). According to the COX proportional hazards model, older patients, involvement of lymph nodes, different types of gastri ccancer and MUC2 expression were significantly associated with poorer outcome of gastric carcinoma patients (β=0.08,β=3.94, β=1.33, β=0.75, respectively, P&lt;0.05). CONCLUSION: MUC1 and MUC2 are good markers of different types of gastric cancer. MUC2 is especially a good marker of mucinous carcinoma. MUCl, MUC2 may interfere with the function of E-cadherin in gastric carcinomas, and have synergic effect on progression of gastric cancers.     

伴淋巴结转移的早期胃癌病理组织形态学研究

目的通过研究早期胃癌发展过程中组织形态学的变迁，预测其淋巴结转移的难易程度。方法以伴淋巴结转移的81例早期胃癌作为转移组，抽取81例不伴淋巴结转移者作为对照组，两组均含11例黏膜内癌，70例黏膜下癌，组织学分类及肿瘤部位相似，具可比性。将各组的肿瘤灶亚分类为表层部、浸润部，各病灶的病理组织形态学依据规范分为分化型、混合型、未分化型。对各病例相关因子进行统计学分析研究。结果浸润部较表层部组织分化程度低下者，转移组为40．7％，较对照组的11．9％为高。转移组表层部的分化型胃癌和未分化型胃癌，其浸润部同一组织学分化程度较对照组为低，其差异有统计学意义（分别为P〈0．01和P〈0．05）。转移组的表层部与浸润部的分化程度合致率为61．7％，明显低于对照组的77．8％，其差异有统计学意义（P〈0．05）。转移组的男女比率为1．9：1，较对照组的3．3：1为低，其差异有统计学意义（P〈0．05）。结论早期胃癌中，癌灶水平方向和浸润先端部的垂直方向组织学分化程度的变化更易出现。浸润部与黏膜同有层癌组织学分化程度不同者，尤其是组织学分化程度趋低下者易出现淋巴结转移。女性较男性更易出现淋巴结转移。     

胃癌组织环氧合酶-2表达与血管内皮生长因子的关系

目的 观察胃癌环氧合酶-2和血管内皮生长因子的表达及相互关系。方法 应用免疫组化法检测胃癌组织COX-2和VEGF的表达状况。结果 32例胃癌中发现COX-2表达阳性22例(68.7％),其中伴淋巴结转移者COX-2表达阳性率80.9％(17/21),高于不伴淋巴结转移者的45.4％(5/11)(P<0.05)。而不同胃癌分期与组织类型之间COX-2表达无显著性差异(P>0.05)。32例胃癌中VEGF表达阳性20例(62.5％),其中COX-2阳性胃癌VEGF表达阳性率77.3％(17/22),而COX-2阴性胃癌VEGF阳性率30％(3/10),两组比较具有显著性差异(P<0.05)。结论 胃癌组织存在COX-2过度表达,且与VEGF表达相关。     

PTEN encoding product： a marker for tumorigenesis and progression of gastric carcinoma

AIM: To detect the expression of PTEN encoding productin normal mucosa, intestinal metaplasia (IM), dysplasia andcarcinoma of the stomach, and to investigate its clinicalimplication in tumorigenesis and progression of gastriccarcinoma.METHODS: Formalin-fixed paraffin embedded specimens from184 cases of gastric carcinoma, their adjacent normal mucosa,IM and dysplasia were evaluated for PTEN protein expressionby SABC immunohistochemistry. PTEN expression wascompared with tumor stage, lymph node metastasis, Lauren'sand WHO's histological classification of gastric carcinoma.Expression of VEGF was also detected in 60 cases of gastriccarcinoma and its correlation with PTEN was concerned.RESULTS: The positive rates of PTEN protein were 100 %(102/102), 98.5 %(65/66), 66.7 % (4/6) and 47.8 %(88/184)in normal mucosa, IM, dysplasia and carcinoma of the stomach,respectively. The positive rates in dysplasia and carcinomawere lower than in normal mucosa and IM (P＜0.01).Advanced gastric cancers expressed less frequent PTEN thanearly gastric cancer (42.9 % v567.6 %, P＜0.01). The positiverate of PTEN protein was lower in gastric cancer with thanwithout lymph node metastasis (40.3 % v563.3 %, P＜0.01).PTEN was less expressed in diffuse-type than in intestinal-type gastric cancer (41.5 % v557.8 %,P＜0.05). Signet ringcell carcinoma showed the expression of PTEN at the lowestlevel (25.0 %, 7/28); less than well and moderatelydifferentiated ones (P＜0.01). Expression of PTEN was notcorrelated with expression of VEGF (P＞0.05).CONCLUSION: Loss or reduced expression of PTEN proteinoccures commonly in tumorigenesis and progression of gastriccarcinoma. It is suggested that PTEN can be an objective markerfor pathologically biological behaviors of gastric carcinoma.     

胃癌组织中Raf激酶抑制蛋白的表达临床意义

目的 探讨Raf激酶抑制蛋白(RKIP)在胃癌中的差异表达及临床意义.方法 采用激光捕获显微切割技术(LCM)获得12例纯化的胃腺癌细胞(GAC)及其癌旁(＞5 cm)胃黏膜上皮细胞(NGEC),应用18O/16O分别标记两种细胞样本酶切后的多肽混合物.结合纳升级液相色谱定量鉴定GAC和NGEC的差异表达蛋白质.免疫印迹法验证差异蛋白RKIP在胃癌中的表达.免疫组化检测RKIP蛋白在胃癌组织(118例)、癌旁胃黏膜组织(70例)、转移的淋巴结组织(35例)的表达.结果 共筛选出78个差异表达蛋白质,其中RKIP蛋白表达水平在GAC中较NGEC明显下调(1:4.37).免疫组化结果显示,RKIP蛋白表达与胃癌的浸润深度、TNM分期及淋巴结转移呈负相关,与分化程度呈正相关(P＜0.05).结论 胃癌组织中RKIP蛋白低表达可能影响胃癌的生物学行为.     

Clinicopathologic factors and molecular markers related to lymph node metastasis in early gastric cancer

AIM: To analyze predictive factors for lymph node metastasis in early gastric cancer.METHODS: We analyzed 1104 patients with early gastric cancer(EGC) who underwent a gastrectomy with lymph-node dissection from May 2003 through July 2011. The clinicopathologic factors and molecular markers were assessed as predictors for lymph node metastasis. Molecular markers such as microsatellite instability, human mut L homolog 1, p53, epidermal growth factor receptor(EGFR) and human epidermal growth factor receptor 2(HER2) were included. The χ2 test and logistic regression analysis were used to determine clinicopathologic parameters.RESULTS: Lymph node metastasis was observed in 104(9.4%) of 1104 patients. Among 104 cases of lymph node positive patients, 24 patients(3.8%) were mucosal cancers and 80 patients(16.7%) were submucosal. According to histologic evaluation, the number of lymph node metastasis found was 4(1.7%) for well differentiated tubular adenocarcinoma, 45(11.3%) for moderately differentiated tubular adenocarcinoma, 36(14.8%) for poorly differentiated tubular adenocarcinoma, and 19(8.4%) for signet ring cell carcinoma. Of 690 EGC cases, 77 cases(11.2%) showed EGFR overexpression. HER2 overexpression was present in 110 cases(27.1%) of 406 EGC patients. With multivariate analysis, female gender(OR = 2.281, P = 0.009), presence of lymphovascular invasion(OR = 10.950, P 0.0001), diameter(≥ 20 mm, OR = 3.173, P = 0.01), and EGFR overexpression(OR = 2.185, P = 0.044) were independent risk factors for lymph node involvement.CONCLUSION: Female gender, tumor size, lymphovascular invasion and EGFR overexpression were predictive risk factors for lymph node metastasis in EGC.     

P27和Fas在胃癌组织中的表达及其临床意义

目的研究P27和Fas在不同病理类型胃癌组织中的表达,以探讨P27和Fas在胃癌发生中的作用与其预后的关系。方法应用免疫组化SP法检测P27、Fas在135例胃癌组织及45例正常胃黏膜组织中的表达情况,胃癌病理组织学分型应用HE染色法。结果胃癌组织中P27、Fas阳性表达率分别为45.93%和42.96%,明显低于正常胃黏膜组织的84.44%和77.78%,胃高中分化腺癌P27阳性表达率(65.45%)高于胃低分化腺癌(33.96%)和黏液癌(40.74%)(P均<0.05),胃高中分化腺癌Fas阳性表达率(60.00%)也明显高于胃低分化腺癌(33.96%)和黏液癌(33.33%)(P均<0.05),P27和Fas阳性表达在胃低分化腺癌与胃黏液癌之间均无显著性差异;无淋巴结转移组P27和Fas阳性表达率分别为48.00%和72.00%,均明显高于有淋巴结转移组的22.50%和40.00%;术后生存期≥5年的胃癌组织中P27表达阳性率(52.63%),Fas表达阳性率(57.89%)均高于生存期<5年组两者阳性表达率(均为16.67%),胃癌组织中P27阳性者的Fas阳性表达率显著高于P27阴性者(P<0.05),二者呈正相关。结论胃癌组织中P27、Fas表达下降,二者在胃癌中的低表达可能与胃癌的分型、恶性程度、淋巴结转移及生存期有关,对胃癌的发生可能起协同作用。检测胃癌组织中P27和Fas的表达有助于判断肿瘤的进展程度和预后。