不同Lauren分型胃癌的临床病理特征及影响胃癌根治术后复发的危险因素分析

摘 要：［目的］ 探讨不同Lauren分型胃癌的临床病理特征、最佳辅助化疗方案,以及影响胃癌根治术后复发的独立危险因素。［方法］ 回顾性分析268例2014年1月1日至2016年9月30日在河北医科大学第四医院行D2根治术且达R0切除的胃癌患者的病历资料及随访资料,采用SPSS23.0、MedCalc15.8及GraphPad Prism7.0软件进行统计学分析及绘图。比较肠型胃癌与弥漫型胃癌的临床病理特征,通过多因素分析筛选影响胃癌根治术后复发的独立危险因素,并根据Lauren分型及TNM分期进行分层,分别筛选引起不同Lauren分型及不同TNM分期胃癌根治术后复发的独立危险因素。［结果］ （1） 肠型胃癌多位于贲门、组织学高分化,与EGFR、HER-2、P53、TOPOⅡ、Ki67高表达相关,其肿瘤直径偏小,淋巴结阳性率偏低,男性占比较多。弥漫型胃癌多位于非贲门部位、组织低分化,与EGFR、HER-2、p53、TOPOⅡ、Ki67低表达相关,其肿瘤直径偏大,淋巴结阳性率偏高;女性所占比例较肠型胃癌患者多,但仍以男性为主。弥漫型胃癌首诊时CA724升高率明显较肠型胃癌高,且更易发生神经受侵及脉管瘤栓。（2）术后辅助化疗方案、肿瘤最大直径、淋巴结阳性率是胃癌复发的独立危险因素,根治术后应用XELOX方案辅助化疗的复发风险是SOX方案的2.323倍。随着肿瘤最大直径的增大和淋巴结阳性率的增高,胃癌复发风险增加。分层分析中,弥漫型胃癌根治术后应用XELOX方案辅助化疗的复发风险是SOX方案的2.209倍,而术后辅助化疗方案不是肠型胃癌根治术后复发的独立危险因素。Ⅲ期胃癌根治术后应用XELOX方案辅助化疗的复发风险是SOX方案的2.161倍,而术后辅助化疗方案不是Ⅱ期胃癌根治术后复发的独立危险因素。（3）淋巴结阳性率是胃癌根治术后复发的独立危险因素,不同Lauren分型胃癌复发的独立危险因素不同。［结论］ （1）不同Lauren分型的胃癌在临床病理特征、对辅助化疗方案的反应及影响预后的独立危险因素方面均各不相同,以Lauren分型指导个体化治疗具有一定的临床意义。（2） SOX方案可作为有效的辅助化疗方案应用于临床,尤其在Ⅲ期及弥漫型胃癌患者中可能获益更佳。     

肠型胃癌的研究进展

摘 要：Lauren分型是最常用的胃癌组织病理学分型之一,它将胃癌分为肠型、弥漫型和混合型。我国是胃癌高发区,其中肠型胃癌在我国的发病率明显高于弥漫型胃癌和混合型胃癌。全文分析了近十几年与Lauren分型相关的文献,从流行病学及病因、发病机制、生物学特征等三个方面对肠型胃癌展开讨论,对肠型胃癌的研究进展作一综述。     

CD44V6在胃癌中的表达及其临床意义

目的：评价转移相关基因CD44V6在胃癌中的表达及其对胃癌进展程度和转移的诊断意义,以及对预后的影响。方法：收集胃癌手术标本75例,应用S－P免疫组化染色技术检测CD44V6蛋白在上述组织中的表达。结果：按Lauren分型,肠型胃癌和弥漫型胃癌的CD44V6阳性表达率分别为77．8％（34／35）和36．6％（11／30）,肠型胃癌阳性率明显高于弥漫型（P＜0．05）,且CD44V6阳性率与肿瘤大小无关（P＞0．05）。结论：CD44V6蛋白的检测对早期预测胃癌进展程度及癌细胞转移潜能、判断胃癌预后具有重要的临床意义。     

HPV16/18DNA在原发性胃癌患者肿瘤组织中的表达及意义

目的探讨人乳头瘤病毒(HPV)16/18 DNA在原发性胃癌患者胃癌组织中的表达情况及其临床意义。方法选取行手术切除且经病理确诊的72例原发性胃癌患者的胃癌组织标本,采用荧光定量聚合酶链反应检测胃癌组织中HPV16/18 DNA的表达情况,分析HPV16/18 DNA表达与原发性胃癌患者临床特征及预后的关系。结果72例原发性胃癌患者中,HPV16/18 DNA的阳性表达率为56.94%。不同Lauren分型、TNM分期、淋巴结转移情况胃癌患者胃癌组织中HPV16/18 DNA的阳性表达率比较,差异均有统计学意义(P﹤0.05);其中,Lauren分型为弥漫型和肠型、TNM分期为Ⅲ期和Ⅱ期、有淋巴结转移的胃癌患者胃癌组织中HPV16/18 DNA的阳性表达率较高。HPV16/18 DNA阳性表达胃癌患者的5年累积生存率低于HPV16/18 DNA阴性表达胃癌患者,但差异无统计学意义(P﹥0.05)。结论原发性胃癌患者胃癌组织中HPV16/18 DNA的阳性表达率较高,且HPV16/18 DNA表达与胃癌患者的Lauren分型、TNM分期及淋巴结转移情况有关,并可能影响患者的预后。     

同源盒转录因子CDX2与Y染色体决定因子SOX9在肠上皮化生及胃癌组织中的表达

目的:研究同源盒转录因子CDX2和Y染色体决定因子SOX9在肠上皮化生(intestinal metaplasia,IM)及胃癌组织中的表达,探讨CDX2和SOX9在IM发生、进展及胃癌发生、发展中的作用及相互关系.方法:选取慢性萎缩性胃炎(chronic atrophic gastritis,CAG)伴IM 24例、癌旁IM 17例、胃癌组织50例,用HE染色对IM及胃癌进行组织学分型,免疫组化法观察CDX2、SOX9蛋白在上述各种胃黏膜组织中的表达,研究二者表达与胃癌临床病理学特征之间的关系.结果:CDX2蛋白表达阳性率在CAG伴IM组、癌旁IM组和胃癌组分别为87.50％、76.47％和62.00％,CAG伴IM组显著高于胃癌组(P＜0.05),CAG伴IM组与癌旁IM组、癌旁IM组与胃癌组之间比较无统计学差异(P＞0.05),肠型胃癌显著高于弥漫型胃癌(77.78％ vs 43.48％,P=0.013).CDX2蛋白在胃癌中的表达与胃癌临床分期、分化程度、Lauren分型及是否有浆膜浸润等有关.SOX9蛋白表达阳性率,在CAG伴IM组、癌旁IM组及胃癌组分别为54.17％、70.59％、80.00％,CAG伴IM组显著低于胃癌组(P＜0.05),CAG伴IM组与癌旁IM组、癌旁IM组与胃癌组之间比较无统计学差异(P＞0.05),肠型胃癌显著高于弥漫型胃癌(92.59％ vs 65.22％,P=0.040).SOX9蛋白在胃癌中的表达与胃癌分化程度、临床分期、Lauren分型和是否淋巴结转移等有关联.胃癌组织中CDX2和SOX9的阳性表达存在显著性负相关(r=-0.391,X2=5.778,P=0.016).结论:CDX2、SOX9在IM及肠型胃癌的发生中可能有重要作用,可做为IM及肠型胃癌预测的特异性指标之一.二者可能在胃癌进展及浸润转移过程中起重要作用,联合检测对选择合适治疗方式及预后判断具有重要价值.     

633例胃癌患者临床病理特征及生存分析

目的 对比不同Lauren分型胃癌的临床病理特征,对其进行生存分析,并筛选预后因子。方法 回顾性分析2007年1月1日—2008年6月30日在哈尔滨医科大学附属肿瘤医院接受手术治疗的胃癌患者的临床病理学资料,将收集到的633例胃癌患者分为肠型胃癌、弥漫型胃癌,对两组的临床病理特征及生存数据等进行统计分析。结果 对比弥漫型胃癌而言,肠型胃癌比例略高(51.66% vs. 48.34%),男性比例较高(2.94:1 vs. 2.03:1,P=0.035),更易发生于老年患者(发病年龄≥60岁比例54.43% vs. 35.94%,P＜0.001)。肠型胃癌预后明显好于弥漫性胃癌(中位生存时间:90.90个月 vs. 37.33个月,P=0.014)。多因素分析显示年龄≥60岁、CA199异常、肿瘤较大、分化较差、浆膜侵犯、初始淋巴结转移、姑息性手术、非幽门切除术是胃癌的不良预后因素。结论 Lauren分型可以较好的反应不同胃癌的临床病理学特征,并指导预后。     

p53在弥漫型胃癌中的表达研究

[目的]研究 p53蛋白表达在胃癌预后中的意义。[方法]采用免疫组织化学LSAB法 ,对152例胃癌组织中 p53蛋白表达进行检测 ,分析 p53表达与临床病理因素及预后之间的关系。[结果]p53蛋白表达阳性率为24 3%(37/152) ,其表达与胃癌各临床病理因素之间无明显相关性。p53表达在肠型胃癌与弥漫型胃癌之间不同 ,生存率分析显示 ,p53表达的不良预后者仅见于弥漫型胃癌而非肠型胃癌。[结论]p53蛋白表达可用于识别弥漫型胃癌中具侵袭性并伴不良预后的亚组胃癌病例     

MMP-9 EGFR在胃癌Lauren''''s分型中的表达及意义

目的：通过检测MMP-9及EGFR在肠型、弥漫型胃癌及癌旁组织中的表达与分布探讨其在胃癌Lauren’s分型中的意叉。方法：对不同分期及分型的74例胃癌标本重新切片，应用免疫组化染色（SP法），计数阳性细胞，统计结果用X^2检验及秩和检验。结果：胃癌组织MMP-9、EGFR阳性表达率显著高于正常胃粘膜（P〈0．01），且其表达强度随胃癌分期的提高而增加，组间比较有显著性差异（P〈0．05）；弥漫型胃癌EGFR阳性表达指数高于肠型胃癌（P〈0．05）。结论：MMP-9、EGFR胃癌的演进与异质化过程发挥着重要的调控作用；胃癌细胞在异常增殖及恶性转化过程中还存在EGFR以外的细胞信号传导系统。     

散发性肠型和遗传性弥漫型胃癌中上皮钙黏附素的表达差异及意义

目的探讨上皮型钙黏附素(E-cadherin,E-cad)在肠型和弥漫型胃癌中的表达情况及其对疾病发生、治疗和预后评估的意义。方法采用免疫组化S-P法对30例正常胃或胃炎粘膜上皮组织、30例散发性肠型胃癌组织和30例遗传性弥漫型胃癌组织中E-cad表达情况进行研究。结果正常或胃炎上皮组织中E-cad全部为阳性表达,表达均匀,散发性肠型胃癌和遗传性弥漫型胃癌组织中E-cad表达均明显减低(P<0.05),表达阳性率分别为63%(19/30)和23%(7/30)。散发性肠型胃癌中E-cad的表达与临床分期相关(P<0.05),遗传性弥漫型胃癌中E-cad的表达与疾病临床分期无关(P>0.05)。结论散发性肠型胃癌E-cad表达降低,呈断续性或者胞浆异位性表达,并与临床分期相关,可能对肠型胃癌的预后评估和治疗具有指导意义。E-cad在遗传性弥漫型胃癌中表达降低更为明显,大部分癌组织中呈现表达缺失,但与分期无关,E-cad表达缺失在遗传性弥漫型胃癌发病的早期可能具有重要作用。     

198例胃癌手术标本Her-2蛋白表达与临床病理的相关性和靶向治疗

背景与目的:通过组织芯片(tissue microarry,TMA)和免疫组织化学(immunohistochemistry,IHC)技术检测人类表皮生长因子受体2(Human epidermal growth factor receptor2,Her-2)在胃癌(gastric carcinoma,GC)中的表达,研究胃癌中Her-2表达的临床意义,为胃癌靶向治疗奠定理论基础.方法:构建包含198例目癌组织和89例正常胃黏膜的组织芯片,应用免疫组化方法检测胃癌中Her-2蛋白的表达.分析Her-2表达与临床病理参数之间的相关性及其对预后的影响.结果:198例胃癌中男性147例,女性51例,男女比例为2.9:1.患者年龄31～85岁,中位年龄66.5岁.按照Lauren's分型分为肠型169例,弥漫型29例.组织芯片免疫组化结果显示198例胃癌细胞中Her-2总表达率为32.8%,而正常胃黏膜无表达.Her-2表达与肿瘤大小、组织类型、肿瘤侵袭深度和TNM分期有关.肠型胃癌的表达率(36.7%)明显高于弥漫型胃癌(10.4%,P=0.005).Her-2蛋白表达与患者性别、年龄、肿瘤部位及预后无关.结论:胃癌中Her-2蛋白的表达率为32%,其表达与胃癌的某些生物学行为有关.肠型胃癌Her-2蛋白表达率明显高于弥漫型胃癌.因此,肠型胃癌患者町能为曲妥珠单抗靶向治疗的主要群体,并有可能从辅助靶向治疗中获益.     

Lauren分型与局部进展期胃癌术前放化疗后肿瘤病理反应相关性分析

目的探讨Lauren分型与局部进展期胃腺癌术前放化疗后肿瘤病理反应相关性。方法选取2013-2019年间中山大学肿瘤防治中心多中心Ⅲ期研究中98例患者,入组患者均有明确的Lauren分型并完成术前放化疗(CRT,46例)或术前化疗(ChT,52例)以及根治手术。分析术前治疗后肿瘤消退分级(NCCN-TRG0-3)、转移淋巴结分期(ypN0-3期)与患者Lauren分型的相关性。病理反应良好(FPR)定义为同时达到TRG0-2和ypN0。结果CRT组中肠型患者比非肠型患者有较高的ypN0率(OR=6.8,95%CI为1.8~25.0,P=0.004)和FPR率(OR=8.0,95%CI为2.2~29.9,P=0.002),而ChT组中Lauren分型则与病理反应无关(P>0.05)。肠型患者中接受术前放化疗患者的病理消退反应率均显著高于术前化疗患者(TRG0-2P=0.033;ypN0P<0.001;FPR P<0.001),而非肠型患者的术后病理反应则与术前治疗方式无关(P>0.05)。结论Lauren分型有可能作为局部进展期胃癌术前放化疗疗效良好的预测因子,并可借以选择、优化术前治疗方式。     

ＨＥＲ-２／ｎｅｕ与胃癌临床病理及预后的相关性研究

目的　研究ＨＥＲ-２／ｎｅｕ基因蛋白表达与胃癌临床病理特征以及预后的相关性,探讨该基因在胃癌中作为预后因素的价值。方法　应用免疫组织化学染色法对２２９例胃癌组织芯片进行ＨＥＲ-２／ｎｅｕ基因蛋白表达的检测,并将检测结果与患者的临床病理特征以及生存随访结果进行统计分析。结果　２２９例胃癌组织中ＨＥＲ-２／ｎｅｕ基因蛋白表达阳性率为１４.８５％,其表达与患者Ｌａｕｒｅｎ分型、组织学分级、肿瘤大小、淋巴结转移和生存时间相关（Ｐ＜０.０５）;Ｌｏｇ-ｒａｎｋ单因素分析显示,ＨＥＲ-２／ｎｅｕ基因蛋白表达与预后相关（Ｐ＜０.０５）;Ｃｏｘ风险比例模型分析显示,ＨＥＲ-２／ｎｅｕ基因蛋白表达、Ｌａｕｒｅｎ分型、肿瘤大小、脉管浸润和ＴＮＭ分期均为独立预后因素（P＜０.０５）。结论　ＨＥＲ-２／ｎｅｕ基因蛋白表达与胃癌的浸润、转移相关,是胃癌独立的预后因素之一。     

Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab.

BACKGROUND: HER-2/neu gene amplification has predictive value in breast cancer patients responding to trastuzumab. We wanted to investigate the frequency and clinical significance of HER-2/neu amplification in gastric carcinoma. PATIENTS AND METHODS: The frequency of HER-2/neu and Topoisomerase IIalpha gene amplification was studied in adenocarcinomas of the stomach (n=131) and the gastroesophageal junction (n=100) by chromogenic in situ hybridization (CISH). Sensitivity of a gastric cancer cell line N87 with HER-2/neu amplification to trastuzumab was studied by a cell viability assay and compared with that of a HER-2 amplified breast cancer cell line SKBR-3. Growth inhibition of N87 cells was also verified in vivo in N87 xenograft tumors. RESULTS: HER-2/neu amplification was present in 16 (12.2%) of the 131 gastric and in 24 (24.0%) of the 100 gastroesophageal adenocarcinomas. Co-amplification of Topoisomerase IIalpha was present in the majority of gastric (63%) and esophagogastric junction cancers (68%) with HER-2/neu amplification. HER-2/neu amplification was more common in the intestinal histologic type of gastric cancer (21.5%) than in the diffuse (2%) or the mixed/anaplastic type (5%, P=0.0051), but it was not associated with gender, age at diagnosis or clinical stage. Presence of HER-2/neu amplification was associated with poor carcinoma-specific survival (P=0.0089). HER-2/neu targeting antibody trastuzumab inhibited the growth of a p185(HER-2/neu) overexpressing gastric and breast carcinoma cell lines (N87 and SKBR-3) with equal efficacy. CONCLUSIONS: HER-2/neu amplification is common in the intestinal type of gastric carcinoma, and it is associated with a poor outcome. HER-2 might be a useful target in this disease, and this hypothesis deserves to be investigated in clinical trials.     

Gastric epithelial histology and precancerous conditions

The most common histological type of gastric cancer (GC) is gastric adenocarcinoma arising from the gastric epithelium. Less common variants include mesenchymal, lymphoproliferative and neuroendocrine neoplasms. The Lauren scheme classifies GC into intestinal type, diffuse type and mixed type. The WHO classification includes papillary, tubular, mucinous, poorly cohesive and mixed GC. Chronic atrophic gastritis (CAG) and intestinal metaplasia are recommended as common precancerous conditions. No definite precancerous condition of diffuse/poorly/undifferentiated type is recommended. Chronic superficial inflammation and hyperplasia of foveolar cells may be the focus. Presently, the management of early GC and precancerous conditions mainly relies on endoscopy including diagnosis, treatment and surveillance. Management of precancerous conditions promotes the early detection and treatment of early GC, and even prevent the occurrence of GC. In the review, precancerous conditions including CAG, metaplasia, foveolar hyperplasia and gastric hyperplastic polyps derived from the gastric epithelium have been concluded, based on the overview of gastric epithelial histological organization and its renewal.     

胃癌HER-2表达的临床意义及血管新生相关性研究

目的 本研究通过检测人表皮生长因子受体-2(HER-2)在胃癌及癌旁组织中的表达,分析其与临床病理特征、血管生成以及术后早期复发的关系,旨在探讨胃癌中HER-2表达的临床意义,为胃癌患者术后制定有效的治疗方案提供理论和临床基础。方法 回顾性分析我科室2012年3月—2013年7月行手术切除的原发胃癌组织398例及相应的癌旁正常组织363例,应用免疫组织化学(Immunohistochemistry,IHC)结合荧光原位杂交(Fluorescence in situ hybridization,FISH)检测肿瘤组织及癌旁正常组织HER-2阳性表达率,同时分析HER-2表达与临床病理特征、血管生成以及术后早期复发的关系。结果 (1)胃癌组织中HER-2的阳性表达率为14.07%(56/398),显著高于癌旁非肿瘤组织0(0/363)(P＜0.05);(2)Lauren分型、肿瘤部位、脉管浸润情况、TNM分期、有无淋巴结转移与HER-2阳性表达相关(P＜0.05),而年龄、性别、肿瘤大小、分化程度、生长方式与HER-2表达无相关性(P＞0.05)。T分期中,T₄期的HER-2表达率高于(T₁+T₂+T₃)期,但无统计学差异(P＞0.05);(3)56例HER-2阳性表达组的微血管密度(Microvessel density,MVD)值为58.63±19.97,342例HER-2阴性表达组的MVD值为49.04±19.25,具有统计学差异,经Spearman等级相关性分析,两组间呈正相关(r=4.33,P＜0.001);(4)早期复发率方面,HER-2阳性表达组1年、1.5年复发率分别为16.00%、38.00%,高于HER-2阴性表达组的8.81%、25.53%,但无统计学差异(P＞0.05)。结论 HER-2在胃癌组织中存在着过度表达,HER-2的过度表达与胃癌患者的Lauren分型、肿瘤部位、脉管浸润情况、TNM分期、有无淋巴结转移具有相关性,而与年龄、性别、肿瘤大小、分化程度、生长方式无关;HER-2的过度表达与肿瘤新生血管生成呈正相关;HER-2的过度表达与术后的早期复发可能存在相关性,需待进一步的随访观察。     

胃癌患者组织病理分型及HP感染相关性分析

目的 探讨胃癌组织病理学分型与HP感染的相关性.方法 随机选取胃癌患者326例,分析入选胃癌患者的肿瘤生长部位、分化程度、组织学类型等病理及临床资料;分析不同分型患者HP、感染情况.结果 HP感染率肠型胃癌患者相对较低,为21.43％,混合型胃癌患者为25.93％,弥漫型胃癌患者最高,高达34.98％,差异有统计学意义.结论 Hp感染与胃癌组织病理分型有关,在弥漫型胃癌中的作用较混合型及肠型胃癌更为重要.     

Loss of the tight junction protein claudin 4 correlates with histological growth-pattern and differentiation in advanced gastric adenocarcinoma

The expression of E-cadherin located in the adherens junction varies with disruption of glandular morphology and loss of differentiation. It has been suggested that the loss of tight junction function is related to tumor differentiation, but little is known about the roles of major proteins, such as claudin 4 and ZO-1, in gastric cancer. The aims of this study were to examine the differences in expression of E-cadherin, claudin 4, and ZO-1 proteins according to the pathological and clinical features of advanced gastric cancer. The expression of E-cadherin, claudin 4, and ZO-1 was analyzed immuno-histochemically using formalin-fixed, paraffin-embedded tissues obtained from 49 patients who underwent radical resection for advanced gastric cancer. Western blot analysis and RT-PCR were performed in representative tumors of the diffuse or intestinal type. Immunostaining for E-cadherin, claudin 4, and ZO-1 was reduced in 69, 69, and 37% of cancers, respectively. Similar patterns of expression were noted for E-cadherin and claudin 4, but ZO-1 expression differed. According to the Lauren classification, the reduced expression of E-cadherin and claudin 4 was more frequent in diffuse than intestinal type tumors (p<0.001). The reduced expression of E-cadherin and claudin 4 correlated with poor differentiation (p<0.05). Western blot analysis and RT-PCR also showed decreased claudin 4 expression in diffuse type tumors and poorly-differentiated adenocarcinoma. The reduced expression of claudin 4 and E-cadherin correlates with disruption of glandular structure and loss of differentiation, which suggests that the dysfunction of claudin 4 may play a role in the disruption of cell-to-cell adhesion in diffuse type gastric cancer and in a loss of differentiation.     

Early gastric cancer: an analysis of 44 cases with emphasis on the prognostic significance of the macroscopic and microscopic growth patterns.

Forty-four consecutive cases of "early gastric cancer" were studied according to the macroscopic classification proposed by the Japanese Gastroenterological and Endoscopy Society and further analyzed in terms of growth patterns. The tumours were then classified into the small mucosal type, the superficially spreading (Super) type and the penetrating growth (Pen) type. The Lauren type (intestinal vs. diffuse), presence of lymphatic and venous invasion, and lymph node metastasis were also assessed. Most elevated tumours showed a superficial growth pattern and were classified as Lauren's intestinal type, whereas depressed lesions were associated with submucosal invasion and were classified as diffuse. Microscopic patterns did not show any correlation with Lauren's classification. Mean duration of follow-up was 67.8 months and the overall actuarial survival was 93%, 80%, and 72%, at 2, 5, and 10 years, respectively. Aside from venous invasion no correlation was found between survival and any of the morphological parameters analysed.     

c-Met、VEGF、EGFR和HER-2在AFP阳性胃癌中的表达研究

背景与目的：甲胎蛋白(alpha fetoprotein,AFP)阳性胃癌(AFP-producing gastric carcinoma,AFPGC)被认为是一种特殊类型的胃癌。疗效比普通胃癌差。针对此类胃癌,探寻其临床病理特征,可能对AFPGC的诊断及个体化治疗具有十分重要的意义。该研究旨在探讨肝细胞生长因子受体c(c-Met)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、表皮生长因子受体(epidermal growth factor receptor,EGFR)和人表皮生长因子受体2(human epidermal growth factor receptor-2,HER-2)等分子标志物在AFPGC中的表达。方法：收集临床上AFPGC(AFP≥10μg/L)组织标本共44例,其中AFP≥200μg/L者共30例,同时收集与该30例AFPGC临床分期基本一致的30例AFP正常胃癌及30例AFP升高(AFP≥200μg/L)的肝细胞癌组织蜡块作为两个对照组,通过免疫组织化学法(EnVision染色方法)检测其c-Met、VEGF、EGFR和HER-2的表达,并通过标记CD34,计数肿瘤微血管密度(microvessel density,MVD),比较3组肿瘤c-Met、VEGF、EGFR、HER-2和MVD表达的异同。主要收集患者的性别、年龄、血清中AFP最高水平、分化程度、肿瘤分期、肿瘤部位、淋巴结转移、肝转移和Lauren分型等临床病例资料,分析AFPGC患者的临床病理特征。结果：AFPGC临床病理特征显示,44例AFPGC组,淋巴结转移率为86.36%(38/44),肝转移率为54.55%(24/44),Lauren分型肠型为36.36%(16/44),弥漫型为56.82%(25/44),混合型为6.82%(3/44)。AFPGC组、AFP正常胃癌组和AFP升高肝细胞癌组c-Met蛋白的阳性表达率分别为73.33%(22/30)、70.00%(21/30)和53.33%(16/30),VEGF蛋白的阳性表达率分别为76.67%(23/30)、56.67%(17/30)和66.67%(20/30),EGFR蛋白的阳性表达率分别为53.33%(16/30)、40.00%(12/30)和73.33%(22/30)。HER-2“++~+++”在AFPGC组、AFP正常胃癌组和AFP升高肝细胞癌组中所占比例分别为36.67%(11/30)、23.33%(7/30)和26.67%(8/30)。MVD值在AFPGC组、AFP正常胃癌组与AFP升高肝细胞癌组中分别为23.03±10.24、21.92±11.45和19.43±7.83。与AFP正常胃癌组相比,AFPGC组的VEGF蛋白表达明显高于前者(P＜0.05);与AFP升高的肝细胞癌组相比,AFPGC组的c-Met蛋白表达明显高于前者(P＜0.05)。结论：AFPGC易发生淋巴结及肝转移,Lauren分型以弥漫型为主。与AFP正常胃癌相比较,AFPGC中VEGF蛋白存在过表达;与AFP升高肝细胞癌相比较,AFPGC组织中c-Met蛋白存在过表达。