Sipa1在胃癌组织中的表达及临床意义

  目的  探讨Sipa1基因（signal-induced proliferation-associated gene 1）在胃癌组织中的表达水平及其与临床病理、预后之间的关系。  方法  分别应用实时荧光定量PCR方法和Western blot法检测43例新鲜胃癌组织及相应癌旁正常组织中Sipa1 mRNA及蛋白的表达量。应用免疫组织化学SP染色法检测122例胃癌和64例正常胃黏膜石蜡组织中Sipa1蛋白的表达水平。  结果  新鲜胃癌组织中Sipa1 mRNA（ΔCt:7.94±1.12）及蛋白（0.305 6±0.108 4）的表达水平较癌旁正常组织（ΔCt:0.531 9±0.072 0;0.531 9±0.072 0）显著下降。胃癌石蜡组织中Sipa1蛋白表达阳性率36.1%较正常胃黏膜石蜡组织中阳性率73.4%低,二者之间差异有统计学意义（P < 0.01）。Sipa1蛋白表达与胃癌分化程度、淋巴结转移、浸润深度、临床分期有关（P < 0.05）,与年龄、性别、肿瘤大小、部位等表达无关（P>0.05）。Sipa1蛋白阴性表达患者比阳性表达患者的5年生存率显著降低（P < 0.01）。  结论  Sipa1基因的表达与胃癌的生物学行为关系密切,对判断预后有参考作用。      

转录因子Sp1在胃癌中的表达及其与预后的关系

目的 研究转录因子Sp1在胃癌及正常胃黏膜组织中的表达特征,并探讨其表达对胃癌患者预后的影响。方法 用免疫组织化学方法,检测65例胃癌原发灶及40例因胃良性病变行胃部分切除标本中的正常胃黏膜组织Sp1表达情况,观察其表达特性并研究该因子表达与患者长期生存率的关系。结果 所测正常胃黏膜组织Sp1表达阳性率仅为12．5％（5／40）。且均表达于正常胃腺的颈部,在成熟细胞较多的胃腺体底部未见有表达。与之相反,Sp1在胃癌组织中则有较高表达率,为53．8％（35／65）。肿瘤组织中Sp1蛋白呈无表达、弱表达及强表达患者的平均生存期分别为1700d、1560d及1026d,彼此间差异有统计学意义（P=0．036）。Sp1蛋白表达与肿瘤侵袭深度及TNM分期密切相关（P=0．001,P=0．026）,而与淋巴结转移数目及Lauren分型无明显相关（P=0．306,P=0．667）。结论 在正常胃黏膜和胃癌组织中,Sp1蛋白表达具有不同的分布特征。Sp1可作为判断胃癌患者预后的一个独立指标,并可能通过除淋巴结转移以外的其他机制促进肿瘤的侵袭和发展。     

PIN1在胃癌组织中的表达及其预后意义

目的 探讨肽基脯氨酰顺反异构酶（PIN1）在胃癌中的表达及其与临床病理学特征及预后的关系。方法 应用组织芯片、免疫组化技术检测134例胃癌组织及对应癌旁组织中PIN1蛋白的表达情况,分析其与临床病理特征及预后的关系。结果胃癌组织中PIN1阳性表达率为33.6％（45／134）,癌旁组织为21.6％（29／134）,差异有统计学意义（P＜0.05）。PIN1表达与胃癌患者TNM分期和远处转移有关（P=0.007,P=0.010）,与其他临床病理特征无关（P＞0.05）。PIN1阳性患者的5年生存率为35.7％,阴性患者为50.6％,差异有统计学意义（P＜0.05）。Cox多因素分析显示,PIN1表达不是胃癌的独立预后因素,而pTNM分期和Lauren分型是胃癌的独立预后因素。结论 胃癌组织中存在PIN1阳性表达,并与TNM分期和远处转移及预后密切相关,可能是潜在的胃癌治疗靶点。     

胃癌组织及区域淋巴结MUC1、CD44v6、nm23表达与胃癌侵袭转移及预后的关系

背景与目的:研究证实胃癌浸润深度和淋巴结转移是多基因及其蛋白表达产物协调作用的结果,寻找与胃癌转移相关的分子生物学标志物有助于胃癌的研究。本实验旨在探讨胃癌组织及区域淋巴结中MUC1、CD44v6、nm23表达与胃癌侵袭转移及预后的关系。方法:采用SP免疫组织化学方法对110例胃癌组织及613枚区域淋巴结中的MUC1、CD44v6、nm23基因蛋白的表达进行检测。结果:①胃癌组织中的MUC1蛋白阳性表达在低分化癌组、浸润型组、T3+T4组、淋巴结转移组、Ⅲ～Ⅳ期组、生存期<5年组分别为84.6%、88.1%、87.3%、91.7%、94.4%、95.5%,CD44v6分别为79.5%、74.6%、79.4%、81.7%、87.0%、87.9%,nm23分别为38.5%、32.2%、30.2%、25.0%、25.9%、18.2%。MUC1和CD44v6表达低分化癌组显著高于高、中分化癌组(78.9%vs57.7%),浸润型组高于局限型组(72.6%vs54.9%),T3+T4组高于T2组(72.3%vs46.8%),淋巴结转移组高于无淋巴结转移组(68.0%vs46.0%),TNMⅢ～Ⅳ期组高于Ⅰ～Ⅱ期组(67.9%vs44.6%),生存期<5年组高于≥5年组(59.1%vs31.8%),各组间差异均具有显著性(P<0.01或P<0.05)。而nm23除分化程度、Borrmann分型不同的两组之间差异无显著性外,T3+T4组低于T2组(51.1%),有淋巴结转移组低于无淋巴结转移组(56.0%),TNMⅢ～Ⅳ期组低于Ⅰ～Ⅱ     

Ⅰd-1和VEGF在胃癌组织中的表达及意义

0引言胃癌是最常见的恶性肿瘤之一,其侵袭与转移是影响患者预后的主要因素。胃癌的侵袭转移是一个复杂的多阶段过程,研究此过程中基因表达的变化,不但有助于阐明胃癌的发生机制,还能为胃癌的治疗及预后判断提供依据,因此而成为人们关注的热点。本研究通过检测Ⅰd-1、VEGF在胃癌中的表     

Tiam1基因在胃癌中的表达及意义

目的 研究Tiam1表达与胃癌浸润转移及其与病人预后的关系.方法 应用FTTC标记的免疫荧光法检测52例人胃癌及20例正常胃黏膜组织中Tiam1蛋白的表达.结果 50例胃癌和20例正常黏膜组织中Tiam1的阳性分别为75%和10%.Tiam1蛋白在胃癌组织中的表达水平与病人的年龄、性别及肿瘤的大小无关(U值分别为0.5132,0.2597,1.1708,P＞0.05);但与胃癌组织的分化程度、浸润深度、淋巴结的转移情况、肿瘤的分期以及病人的五年存活情况具有显著相关性(U值分别为3.1838,3.0430,2.2597,5.1035,4.3266,P＜0.05).随着胃癌组织分化程度的降低,浸润深度的加深,Tiam1蛋白染色阳性率逐渐上升,Tiam1阳性率增高提示预后不良.结论 Tiam1蛋白的表达与胃癌浸润转移呈相关关系,并与多种临床病理因素相关,可为胃癌浸润转移的防治和病人的预后判定提供有价值的参考.     

microRNA-214在胃癌组织中的表达情况及临床意义

目的探讨微小RNA(miRNA)-214在胃癌组织中的表达情况及临床意义。方法选取47例胃癌患者的胃癌组织标本及对应的癌旁组织标本,采用实时荧光定量聚合酶链反应(qRT-PCR)检测胃癌组织(n=47)和癌旁组织(n=47)中miRNA-214的表达情况,分析miRNA-214表达与胃癌患者临床特征的关系。结果胃癌患者胃癌组织中miRNA-214的相对表达量明显高于癌旁组织(P<0.01)。不同TNM分期、分化程度、淋巴结转移情况的胃癌患者胃癌组织中miRNA-214的相对表达量比较,差异均有统计学意义(P<0.05);不同性别、年龄、肿瘤直径的胃癌患者胃癌组织中miRN A-214的相对表达量比较,差异均无统计学意义(P>0.05)。3年无瘤生存的23例胃癌患者胃癌组织中miRNA-214的相对表达量与3年复发或转移的24例胃癌患者胃癌组织中miRNA-214相对表达量比较,差异有统计学意义(P<0.05)。miRNA-214高表达、TNM分期为Ⅲ~Ⅳ期、有淋巴结转移和低分化均是胃癌患者3年无瘤生存的独立危险因素(P<0.05)。结论miRNA-214在胃癌组织中呈相对高表达,miRNA-214高表达、TNM分期为Ⅲ~Ⅳ期、有淋巴结转移和低分化均是胃癌患者预后的独立危险因素。     

粘蛋白MUC1和MUC2在胃癌组织中的表达及其预后意义

目的 :探讨粘蛋白MUC1和MUC2在胃癌组织中的表达及意义。方法 :采用免疫组织化学法的SP法检测 86例胃癌组织及 2 0例人正常胃粘膜中的MUC1和MUC2的表达。结果 :在正常胃粘膜中MUC1阳性表达率为 10 0 % ,而MUC2无阳性表达。在胃癌组织中MUC1和MUC2的表达率分别为 5 8 14 %和 6 3 95 %。胃癌组织中MUC1和MUC2的表达与肿瘤大小、浸润深度及分化程度无关 (P >0 0 5 ) ,但Ⅰ～Ⅱ期、淋巴结无转移组MUC1的表达明显比Ⅲ～Ⅳ期、淋巴结转移组低 ,而MUC2表达明显增高 (P <0 0 1)。Kaplan Meier分析发现MUC1高表达和MUC2低表达患者的生存时间明显低于MUC1低表达和MUC2高表达患者 (P <0 0 1)。结论 :MUC1和MUC2可预示胃癌的转移潜能 ,两者联合表达可作为评估预后的参考指标。     

GLI1蛋白在胃癌组织中的表达及临床意义

目的:探讨胶质瘤相关癌基因1(GLI1)在胃癌组织中的表达及临床意义。方法:收集2014年1月至2014年12月我院胃肠外科收治的经病理确诊行根治性手术的78例胃癌患者肿瘤组织及其邻近的正常胃组织标本。采用免疫组化染色方法检测胃癌及其邻近正常胃组织中GLI1表达情况,分析GLI1的表达与胃癌患者临床病理特征之间的相关性。结果:GLI1蛋白在胃癌组织中表达显著高于邻近正常胃组织（75.6% vs 26.9%,P＜0.001）,且GLI1的表达与肿瘤大小、肿瘤浸润深度、脉管侵犯、TNM分期、淋巴结转移有关,差异有统计学意义（P＜0.05）,而与性别、年龄、肿瘤部位、分化程度、神经侵犯无关（P＞0.05）。生存分析利用Kaplan-Meier法,结果提示胃癌患者中GLI1高表达组总体生存时间显著低于低表达组,二者差异有统计学意义(P＜0.000 1)。结论:GLI1在胃癌组织中异常高表达,参与胃癌的发生发展及预后,未来可能成为胃癌基因治疗的新靶点。     

淋巴结转移阳性比率在预测T_3期胃癌患者预后中的价值

背景与目的:现有的TNM分期以转移淋巴结数作为淋巴结分期的标准,故对清扫的淋巴结数目有要求的同时,也可能因淋巴结清扫范围的不同而产生分期偏移.本研究将探讨淋巴结转移阳性比率在预测T3期胃癌患者预后中的应用价值.方法:回顾性分析273例接受胃癌D2根治手术且淋巴结清扫总数≥15枚的T3期胃癌患者的临床资料,分析淋巴结转移阳性比率及淋巴结转移阳性枚数与清扫的淋巴结总数间的相关性及淋巴结转移阳性比率在预测T3期胃癌患者预后中的价值.结果:当清扫的淋巴结≥15枚时,淋巴结转移阳性比率的高低与检出的淋巴结总数无相关性(r=0.069,P0.05),而淋巴结转移阳性枚数与检出的淋巴结总数具有相关性(r=0.237,P<0.05).单因素分析发现淋巴结转移阳性比率影响T3期胃癌患者预后(Log-rankχ2=92.414,P<0.01),多因素分析显示淋巴结转移阳性比率是影响T3期胃癌患者预后的独立因素之一.淋巴结转移阳性比率预测T3期胃癌患者预后的ROC曲线下面积与淋巴结转移阳性枚数预测结果的差异无显著性(P0.01).结论:淋巴结转移阳性比率是影响T3期胃癌患者预后的独立因素;在淋巴结清扫范围足够的情况下,淋巴结转移阳性比率预测T3期胃癌患者预后的准确性与淋巴结转移阳性枚数的预测能力相当,在预测T3N3期胃癌预后方面,淋巴结转移阳性比率较淋巴结转移阳性个数更为准确、客观.     

ANXA1在胃癌和淋巴转移灶中的表达及其临床意义

目的 通过检测ANXA1在胃癌及其淋巴转移灶中的表达,探讨ANXA1表达与胃癌患者临床病理特征、mTOR通路激活状态及预后的关系。方法 在含有121例胃癌及淋巴转移灶的组织芯片上,利用免疫组化检测ANXA1、p-mTOR在淋巴转移灶中的表达,分析ANXA1与临床病理特征、p-mTOR及预后关系。结果 免疫组化显示,ANXA1在胃癌淋巴转移灶中的阳性表达率为14.9％（18／121）,低于胃癌原发部位的35.5％（43/121）;而p-mTOR在胃癌淋巴转移灶中的阳性表达率为61.2％（74／121）,高于胃癌原发部位的51.2%（62/121）。胃癌淋巴转移灶中ANXA1的表达与原发肿瘤部位、胃壁侵犯、p-mTOR以及组织学分化高度相关（P＜0.05）。生存分析显示,ANXA1是判断胃癌患者预后的独立指标。结论 ANXA1缺失表达在胃癌淋巴结转移过程中可能起着重要作用,ANXA1与胃癌患者的预后密切相关。     

Clinical significance of skip metastasis in patients with gastric cancer

Background Metastasis appearing to bypass or skip tiers of lymph nodes (LNs) has been referred to as skip metastasis. The clinical impact of skip metastasis in gastric cancer remains unclear. Methods In patients with gastric cancer, the clinicopathological features and postoperative prognoses of 21 patients with skip metastasis were evaluated and compared with findings in patients with group 1 (N1) or group 2 (N2) LN metastasis. Results Of the 21 patients with skip metastasis, 9 patients had metastasis in the LN along the common hepatic artery (No. 8a), 8 patients had metastasis in the LN along the left gastric artery (No. 7), 2 patients had metastasis in LNs No. 7 and No. 8a, 1 patient had metastasis in the LN at the splenic hilum (No. 10), and 1 patient had metastasis in LN No. 10 and the LN along the splenic artery (No. 11). The mean diameter of the tumors in the patients with skip metastasis was 5.7 ± 2.4 cm, which was significantly smaller than those in the N1 patients (7.9 ± 4.1 cm) and N2 patients (9.3 ± 4.6 cm). The incidence of serosal invasion, lymphatic vessel invasion, and peritoneal metastasis was lower in patients with skip metastasis compared with N2 patients. The 5-year survival rates were 70.2%, 62.0%, and 31.2% in patients with skip metastasis, patients with metastasis in group 1 LNs, and those with metastasis in group 2 LNs, respectively. The prognosis of patients with metastasis in group 2 LNs was significantly worse than that of patients with either skip metastasis (P = 0.0029) or metastasis in group 1 LNs (P < 0.0001). Conclusion Our data indicate that both the clinicopathological characteristics and the prognoses of patients with skip metastasis were similar to those of patients with N1 LN metastasis, but these features were not similar to those in patients with N2 LN metastasis. The sites of skip metastasis presented in the current study may be the key for applying the concept of the sentinel node in gastric cancer.     

Extra-nodal metastasis should be classified separately from lymph node metastasis in gastric cancer

IntroductionExtra-nodal metastasis (ENM) is defined as a tumor nodule without histological evidence of a lymph node structure. Although ENM has pathological features distinct from those of metastatic lymph nodes, both ENM and metastatic lymph nodes are considered within the same category in the pathological nodal (pN) classification. This study aimed to clarify the clinicopathological characteristics and prognostic relevance of ENM in gastric cancer patients who underwent curative gastrectomy.Materials and methodsWe retrospectively evaluated 1207 Japanese patients who underwent curative gastrectomy at a single center between January 2009 and December 2013. All resected specimens were fixed in 10% formalin, processed, and stained using hematoxylin and eosin, and subsequently reviewed by two pathologists. Survival times were analyzed using the Kaplan-Meier method, and independent prognostic factors were identified using a Cox proportional hazards regression model.ResultsPatients who were ENM-positive had significantly poorer overall survival; multivariable analysis revealed that independent prognostic factors were older age (hazard ratio [HR]: 3.68, 95% confidence interval [CI]: 2.60–5.20), higher pathological tumor classification (HR: 2.28, 95% CI: 1.43–3.62), presence of metastatic lymph nodes (HR: 1.57, 95% CI: 1.0–2.36), and ENM-positive status (HR: 2.33, 95% CI: 1.48–3.66). ENM-positive patients had similar survival outcomes to those of ENM-negative patients with ≥16 metastatic lymph nodes.ConclusionsAmong Japanese patients with gastric cancer who underwent curative gastrectomy, ENM was an independent prognostic factor with a prognostic significance different from that of lymph node metastasis. These results suggest that ENM and lymph node metastasis should be classified separately.     

Two rare cases of node-positive differentiated gastric cancer despite their infiltration to sm1, their small size, and lack of lymphatic invasion into the submucosal layer

Early gastric cancer without lymph node metastasis has been reported after the analysis of many cases, and a consensus has been reached about this condition. We report two cases of node-positive differentiated sm1 gastric cancer without lymphatic invasion into the submucosal layer. Case 1 was a 73-year-old man who underwent EMR for 0-IIc early gastric cancer (EGC) on the gastric angle, with a histological diagnosis of tub1. Pathological examination revealed a 0-IIc lesion that was 12 mm in size and sm1 in invasion depth without lymphatic-vascular invasion. However, the infiltration in the submucosal layer was relatively wide. The patient subsequently underwent distal gastrectomy with D2 lymph node dissection. Pathological examination revealed level 2 lymph node metastasis. Case 2 was a 62-year-old woman who underwent ER for a 0-I+IIc-type EGC on the greater curvature of the antrum, with a histological diagnosis of tub1. Pathological examination revealed a 0-I+IIc-type lesion that was 15 mm in size and sm1 in depth. Lymphatic invasions in the muscularis mucosa were found, but none were seen in the submucosal layer. Two years later, follow-up computed tomography (CT) showed a lymph node swelling in the infrapyloric region. Distal gastrectomy with D2 dissection was then performed, and pathological examination revealed level 1 lymph node metastasis. Although the lesions in both patients satisfied the criteria of Gotoda et al. for minimal risk of nodal involvement, lymph node metastasis was observed in these patients. Curative surgery with lymph node dissection is thus required in patients with wide infiltration of the submucosal layer or lymphatic invasion in the muscularis mucosa.     

Prognostic value of extracapsular invasion and fibrotic focus in single lymph node metastasis of gastric cancer

BACKGROUND: Histological findings of metastatic lymph nodes are important prognosticators in patients with gastric cancer. The aim of this study was to clarify the clinical significance of various pathological characteristics of the early phase of lymph node metastasis in patients with gastric cancer, by selecting patients with tumors that had single lymph node metastases, no serosal invasion, and no metastases to the peritoneum, liver, or distant organs. METHODS: Seventy-eight patients were eligible and were entered in this study. These patients were subdivided according to the following histological characteristics of the one metastatic lymph node: size of the metastasis (i.e., amount of tumor cells [AT]), proliferating pattern (PP), intranodal location (IL), and the presence or absence of extracapsular invasion (ECI) and/or fibrotic focus (FF). Associations between clinicopathological factors, survival, and the nodal findings were examined. RESULTS: There were no correlations between AT or PP and any clinicopathological factors. IL was significantly correlated with venous invasion and the pathological characteristics of the primary tumor. ECI and FF were observed significantly more frequently in pT2 than in pT1 cancer. Overall survival (OS) differed significantly according to depth of invasion, venous invasion, and the presence or absence of ECI or FF, although OS was not affected by AT, PP, or IL. The 10-year overall survival rates of patients with and without ECI were 50% and 80%, respectively, while these rates for patients with and without FF were 50% and 79%, respectively. Multivariate analysis revealed that ECI and FF were significant prognosticators of survival. CONCLUSION: These results strongly suggested that the presence of ECI or FF could affect the survival of patients with gastric cancer.     

Preoperative lymph node size is helpful to predict the prognosis of patients with stage III gastric cancer after radical resection

Objective

To investigate the association between preoperative lymph node size (Ns) and prognosis of radical gastrectomy for gastric cancer.

SRC1在胃癌中的表达及其与预后的关系

目的 探讨类固醇受体辅助活化因子-1(Steroid receptor coactivator 1,SRC1)蛋白在胃癌组织中的表达及其与患者临床病理参数和预后的相关性。方法 收集36例胃癌组织及其配对的癌旁组织,qRT-PCR法及Western blot法检测SRC1mRNA和蛋白的表达水平。应用免疫组化方法检测286例胃癌组织中SRC1蛋白的表达情况,分析SRC1蛋白表达与胃癌临床病理参数的关系及其对患者预后的影响。结果 与癌旁组织相比,胃癌组织中SRC1mRNA表达水平明显降低(P=0.004),SRC1蛋白表达水平也明显降低。SRC1蛋白的表达强度与胃癌患者临床病理参数无显著关系。Kaplan-Meier生存曲线分析发现高表达SRC1组5年生存率显著高于低表达组(P=0.009)。Cox回归分析结果显示低表达SRC1(P=0.002)、肿瘤侵袭T_4a~T_4b(P=0.004)、淋巴结转移N(P=0.038)、远处转移M1(P＜0.001)是独立影响总生存时间的预后不良因素。SRC1低表达较高表达患者预后差。结论 胃癌中SRC1的表达明显降低,胃癌组织中的SRC1表达水平可作为独立的胃癌预后不良因素,其过低表达与胃癌的发展密切相关,可能作为一个抑癌基因及判断胃癌患者预后的标志物。     

Neoadjuvant chemotherapy followed by surgery in gastric cancer patients with extensive lymph node metastasis

Gastric cancer with extensive lymph node metastasis (ELM) is usually considered unresectable and is associated with poor outcomes. Cases with clinical enlargement of the para-aortic lymph nodes and/or bulky lymph node enlargement around the celiac artery and its branches are generally dealt with as ELM. A standard treatment for gastric cancer with ELM has yet to be determined. Two phase II studies of neoadjuvant chemotherapy followed by surgery showed that neoadjuvant chemotherapy with S-1 plus cisplatin followed by surgical resection with extended lymph node dissection could represent a treatment option for gastric cancer with ELM. However, many clinical questions remain unresolved, including the criteria for diagnosing ELM, optimal regime, number of courses and extent of lymph node dissection.     

Prognostic significance of the metastatic lymph node ratio in T3 gastric cancer patients undergoing total gastrectomy

Aims and background: The International Union Against Cancer tumor node metastasis classification is routinely applied for evaluating the prognosis of patients with gastric cancer. However, results are still heterogeneous. This study was therefore carried out to evaluate the prognostic significance of the metastatic lymph node (LN) ratio in T3 gastric cancer patients undergoing gastrectomy. Methods: Clinical data of 109 LN-positive cases were retrospectively analyzed. Spearman correlation analysis was used to determine the correlation coefficiency. Survival time was determined by Kaplan-Meier and Log-rank test. Multivariate analysis was performed using the Cox model. ROC curves were used to compare the accuracy of the number of metastatic LN and metastatic LN ratio. Results: The metastatic LN ratio did not correlate with the number of LN when at least 15 nodes were dissected, whereas the number of metastatic LN did. Univariate analysis showed that the metastatic LN ratio influenced significantly the survival time, while multivariate analysis revelaed it to be a major independent prognostic factor. Conclusions: The metastatic LN ratio can be used as a major independent prognostic factor for the patients with T3 gastric cancer.