胃癌组织Snai2和E-cadherin表达及其与淋巴结转移关系的研究

目的:观察E-cadherin蛋白和Snai2蛋白在胃癌组织中的表达及其与淋巴结转移的关系.方法:采用免疫组织化学方法(SP法)检测54例胃癌组织和癌旁组织中E-cadherin蛋白和Snai2蛋白的表达情况.结果:E-cadherin蛋白在胃癌组织中表达率(33.33％)明显低于癌旁组织(100.00％,P＜0.05),而Snai2蛋白在胃癌组织中表达率(61.11％)明显高于癌旁组织(20.37％,P＜0.05);两者表达呈负相关(r=-0.564,P＜0.01)且均与胃癌浸润深度和淋巴结转移明显相关,P＜0.05.淋巴结转移阳性胃癌组织中Snai2蛋白阳性表达且E-cadherin蛋白阴性表达者为78.57％,而淋巴结转移阴性者为26.92％,两者差异有统计学意义,P＜0.01,Snai2蛋白阳性且E-cadherin蛋白阴性与淋巴结转移阳性呈显著正相关,P＜0.01.结论:Snai2和E-cadherin在胃癌发生演进过程中有重要作用,Snai2可能抑制E-cadherin表达导致上皮—间质转化而促进胃癌浸润转移.联合检测Snai2与E-cadherin表达情况对术前评估胃癌琳巴结转移状况有一定临床意义.     

胃癌淋巴结微转移的研究进展

胃癌根治术后,尤其无淋巴结转移的早期胃癌根治术后仍有一定复发率,这促使研究者采用更敏感的方法追踪可能存在而被漏诊的转移,尤其是淋巴结微转移。随着检测技术的进步,微转移检出率明显提高。但其对胃癌分期、预后等诸多方面的影响仍有较大争议,因此,尚无共识的临床处理策略。而随着内镜技术治疗早期胃癌的兴起,如何平衡患者术后生命质量和治疗安全的关系,避免漏诊存在微转移的淋巴结,使得微转移研究更加迫切。     

五十例胃癌淋巴结转移情况分析

胃癌的治疗仍以手术切除为主,究竟如何切除才能提高五年治愈率是目前大家讨论的主要课题。我们对五十例胃癌的淋巴结转移情况进行了统计和分析,其的是为了研究胃癌的淋巴结转移规律选择合理的手术方式,确定淋巴结的清扫范围,提高术后生存期,探讨胃癌的生物学特性及对予后的判定等。资料与方法五十例胃癌系我院住院病人根治切除的标本。研究的标准是按着1978年全国胃癌会议制定的方案。胃周淋巴结是根据日本胃癌研究会的规定为十六组,并且按着病灶的不同部位分成相应的ⅠⅡⅢ站。术中切除的淋巴结放入有     

胃癌淋巴结大小与转移的关系

[目的]评估胃癌淋巴结大小与转移的相关性。[方法]分析115例胃癌患者手术摘取的淋巴结数目、最大径、病理结果,探讨转移频数与淋巴结大小的相关性。[结果]115例标本共2252个淋巴结,556个淋巴结(24.7%)有转移,转移淋巴结平均直径(10.1±4.2)mm,而无转移淋巴结是(5.9±3.5)mm(P<0.01)。1～5mm和6～9mm淋巴结转移率分别为12.3%(112/908)和26.2%(238/910);10～14mm和≥15mm淋巴结转移率分别为40.5%(130/321)和67.3%(76/113),后3组间存在显著差异(P<0.05)。40例无淋巴结转移患者中,33例患者(82.5%)至少有一个淋巴结≥10mm,12例患者(30%)至少有一个淋巴结≥15mm。[结论]淋巴结大小不能作为评估胃癌淋巴结转移的可靠参数。     

胃癌淋巴结转移规律的研究

目的在于指导合理清除淋巴结。方法应用近２０年胃癌根治切除病例。研究其淋巴结转移率、计量、分型、分级、以及分子水平研究。结果淋巴结转移在４枚以下、Ｎ１、Ｎ２者,扩大淋巴结清除术、可获良效。每级５年生存率相差２０％上下。大结节融合型转移轻,小结节孤立型转移严重。ＤＮＡ、肿瘤标志物,Ｅ－ＣＤ显示了预测转移程度的潜能。结论胃癌转移分型、计量、分级研究与分子水平研究,有助于正确指导合理淋巴结清除术。     

实时荧光定量PCR检测CK18对胃癌淋巴结微转移的诊断价值

[目的]建立细胞角蛋白18（CK18）实时荧光定量PCR（RTFQ-PCR）检测系统,定量检测CK18在胃癌淋巴结中的表达水平．发现淋巴结微转移,从而提高胃癌淋巴结转移诊断的阳性率。[方法]应用TaqMan探针实时荧光定量PCR方法,以CK18作为淋巴结微转移的标志基因,制备CK18表达序列的标准品,并建立标准曲线。定量检测24例病理证实无淋巴结转移的胃癌患者199枚淋巴结的CK18 mRNA拷贝数。[结果]RTFQ—PCR检测CK18 mRNA的95％CV值为2．38％,敏感性达10个拷贝。24例病理无淋巴结转移的胃癌患者,15例CK18 mRNA阳性。阳性率为62．5％（15,24）。RTFQ-PCR检测CK18 mRNA的量值水平,最小值为2．57×10^2,最大值1．08×10^8。[结论]应用RTFQ-PCR方法,以CK18作为淋巴结微转移的标志基因．可提高胃癌淋巴结转移的检出率．能够发现组织病理学检查不能发现的微转移灶,并可能对微转移分级有益。     

胃癌活检标本癌转移相关基因表达与淋巴结转移的预测

目的：检测活检标本中10项癌转移相关基因的表达与淋巴结转移的关系，探讨它们在预测胃癌淋巴结转移中的应用价值。方法：采用免疫组化S-P法，检测44例胃镜活检胃癌粘膜CD44V6、E-cadherin、VEGF、EGFR、p53、nm23-H1、Fas、FasL、Cath-B、Cath-D的表达情况，分析其与胃癌淋巴结转移的相关性。结果：VEGF和EGFR与胃癌淋巴结转移呈正相关，Fas与胃癌淋巴结转移呈负相关。VEGF( )EGFR( )、VEGF( )E-cadherin(-)、VEGF( )Fas(-)及EGFR( )Fas(-)等4对两两组合显示与胃癌淋巴结转移有关。3个因素预测胃癌淋巴结转移的敏感性和特异性偏低，4对两两组合可提高预测胃癌淋巴结转移的特异性，但敏感性明显降低。结论：检测活检标本癌转移相关基因的表达在预测胃癌淋巴结转移的临床实际应用意义不大。     

早期胃癌组织中上皮钙粘蛋白表达与淋巴结微转移及临床病理的关系

背景与目的:早期胃癌淋巴结微转移问题日益受到关注,胞浆角蛋白(cytokeratin,CK)染色是识别上皮源性恶性肿瘤细胞的重要方法,本研究拟探讨早期胃癌原发灶上皮钙粘蛋白(epithelial cadherin,E-cad)的表达情况与淋巴结内出现微转移之间的关系及临床意义.方法:用免疫组织化学染色的方法对162例早期胃癌患者的4 522枚淋巴结进行苏木精-伊红(HE)和胞浆角蛋白(cytokeratin,CK)染色,并对其中135例患者的原发灶切片进行E-cad染色,结合临床病理资料和随访结果进行分析.结果:HE染色发现的淋巴结转移率为6.8%(11/162),而CK染色发现的淋巴结转移率为26.5%(43/162),二者差异有统计学意义(P＜0.001).在151例HE染色未见淋巴结转移的患者中通过CK染色发现了32例(21.2%)有淋巴结微转移,且淋巴结微转移多见于原发灶直径大于1.0 cm,组织分化不良,肿瘤浸润较深的(如浸及粘膜下层),淋巴管和血管受累,以及E-cad低表达标本(P＜0.05).原发灶E-cad的低表达率为57.0%(77/135),与淋巴结出现微转移有密切关系,有淋巴结微转移患者的5年生存率比没有微转移者明显低(P＜0.01).结论:肿瘤直径大于1.0 cm,组织分化不良,较深的浸润,淋巴管或血管受累,以及E-cad低表达是早期胃癌患者出现淋巴结转移的高危因素.     

进展期胃癌淋巴结转移的临床分析

目的 探讨进展期胃癌淋巴结转移的规律。方法 回顾2003年9月至2004年9月间132例进展期胃癌术后病理资料，分析其淋巴结转移的情况。结果 肿瘤直径〉5cm、侵及浆膜层、浸润型及分化差者的淋巴结转移率显著高于直径〈5cm、侵及肌层、限局型及分化好者，肿瘤部位不同，好发转移淋巴组别也不同。结论 进展期胃癌淋巴结转移与肿瘤大小、浸润深度、大体类型、分化程度相关，转移淋巴结的分布与肿瘤部位有关。     

临床规范化胃癌淋巴结转移评估的研究进展

淋巴系统转移是影响胃癌预后的关键性因素之一。临床上如何做到规范化淋巴结转移的评估是准确进行疾病分期和选择最佳治疗方案的基本前提。目前,国内、外针对如何做到规范化胃癌淋巴结转移评估尚未达成共识。本文从胃癌淋巴结转移的机制、常见的评估方式、分期的演变及淋巴结获取的保障等方面进行综述,以期评价出最为有效的临床规范化胃癌淋巴结转移评估的可行方式。      

结肠癌组织中Tiam1的表达与淋巴管生成之间的关系

目的:我们的实验旨在探讨T淋巴瘤侵袭转移基因1(T-cell lymphoma invasion and metastasis1,Tiam1)与结肠癌淋巴管生成的关系。方法:应用SP免疫组化法检测50例经4%甲醛固定、石蜡包埋结肠癌组织中Ti-am1、VEGF-C/D以及淋巴管密度(LMVD)的表达情况。结果:Tiam1阳性表达组VEGF-C阳性率为64.3%,Ti-am1阴性表达组VEGF-C阳性率为25.0%,二者差异有统计学意义,P=0.039;Tiam1阳性表达组LMVD为11.35±3.34,Tiam1阴性表达组LMVD为7.38±2.27,二者差异有统计学意义,P=0.002。结论:Tiam1过量表达可能与结肠癌淋巴管生成有关。     

T淋巴瘤侵袭转移诱导因子1在胃癌组织中的表达及其临床意义

目的观察胃癌和正常胃粘膜组织中T淋巴瘤侵袭转移诱导因子1(Tlymphomainvasionandmetas tasisinducingfactor1,Tiam1)蛋白的表达情况并探讨其临床意义。方法应用链酶亲和素-生物素过氧化物酶复合物免疫组化法检测60例经福尔马林固定、石蜡包埋之胃癌及正常胃粘膜组织标本中Tiam1蛋白的表达情况并分析其与胃癌临床病理参数间的关系。结果Tiam1蛋白在正常胃粘膜组织中呈阴性染色(0/60,0.00%),但在胃癌组织中则呈阳性染色(47/60,78.33%),两者间统计学差异非常显著(P<0.01);且随胃癌组织分化程度的降低、浸润深度的增加、TNM分期的升高及伴有淋巴结转移的发生,Tiam1蛋白染色阳性率逐渐升高,统计学意义显著(P<0.05)。但Tiam1蛋白表达水平与胃癌患者的性别、年龄、癌变原发部位及癌肿大小无关,统计学意义不显著(P>0.05)。结论Tiam1蛋白的表达与胃癌浸润、转移密切相关并有可能作为反映其生物学行为的一种新型标志物。     

宫颈癌患者淋巴结CK19 mRNA的检测及其临床意义

背景与目的：采用RT—PCR技术检测CK19（cytokeratin 19）mRNA的转录，可在部分恶性肿瘤患者中检测到常规病理学方法不能检测到的隐性微转移。本研究旨在检测宫颈癌患者盆腔淋巴结组织特异性标志物（CK19mRNA）的表达，并探讨其临床意义。方法：采用RT—PCR技术检测Ⅰ～Ⅱ期宫颈癌患者盆腔淋巴结CK19 mRNA的转录。生存曲线用Kaplan—Meier转录。生存率比较采用Log—rank检验。结果：32例宫颈癌患者共检测淋巴结标本206枚，经常规病理组织学方法检测到24枚淋巴结有癌转移，阳性率为12％（24／206）；经RT—PCR法检测到44枚淋巴结表达CK19 mRNA，检出率为21％（44／206）。RT—PCR法与常规病理组织学方法比较，差异有显著性（P〈0．01）。常规HE染色阴性的182枚淋巴结中，29枚检测到CK19mRNA的特异性条带，微转移的检出率为15．9％（29／182）。低分化患者的淋巴结CK19检出率为87．5％（7／8）显著高于中～高分化患者的检出率33．3％（8／24）（P〈0．05）。而淋巴结CK19的检出率与年龄、临床分期、组织学类型、宫颈肿瘤大小、肌层浸润深度、宫旁浸润、脉管癌栓均无明显关系（P〉0．05）。淋巴结CK19 mRNA阳性患者的4年无瘤生存率为58％；而淋巴结CK19 mRNA阴性患者的4年无瘤生存率为76．5％，差异无显著性（P〉0．05）。结论：与传统的病理组织学比较，采用RT—PCR技术检测CK19 mRNA转录能显著提高淋巴结微转移的检出率，预后判断有待增大病例数进一步研究。     

CK8/18 expression, the basal phenotype, and family history in identifying BRCA1-associated breast cancer in the Ontario site of the breast cancer family registry

BACKGROUND.

BRCA1‐associated breast cancer had been shown to be morphologically and genetically distinct from sporadic cancers. The aim of this study was to determine the association of CK8/18 with BRCA1‐associated tumors and if, by using CK8/18 and basal biomarkers in conjunction with morphologic features and family history characteristics, the specificity of the BRCA1‐associated tumor profile in a pathologically well‐characterized cohort would be improved.

METHODS.

Fifty‐eight patients with known BRCA1 germline mutations and 221 control (familial non‐BRCA) patients were selected from the Ontario Familial Breast Cancer Registry. From this database, information on family history and morphologic features was abstracted. Tissue microarrays were constructed and immunohistochemistry to determine expression of several biomarkers was performed. After a logistic regression fit, a best‐subsets variable‐selection procedure using model performance and predictive ability measures was applied to find a best predictor to distinguish BRCA1‐associated tumors from non‐BRCA associated tumors.

RESULTS.

BRCA1‐associated tumors differed significantly from control tumors in terms of morphology, family history, and biomarker profile. CK8/18 was highly significantly associated with BRCA1 tumors. Consistently, BRCA1 cancers showed low levels of CK8/18 compared to non‐BRCA tumors, whether they were basal‐like or not. A combination of 7 factors, including CK8/18 and family history, best predicted the BRCA1‐associated cancers.

CONCLUSIONS.

CK8/18 expression was independently associated with BRCA1‐associated breast cancers. Reduced CK8/18 expression in conjunction with the basal‐like phenotype and family history may have improved the ability to identify which tumors were likely to be associated with a BRCA1 germline mutation and thereby help streamline genetic testing. Cancer 2011. © 2010 American Cancer Society.     

Tiam1与胃癌侵袭及转移相关性研究

目的 检测T淋巴瘤侵袭转移诱导因子1(Tiam1)在正常胃黏膜组织、不典型增生组织、胃癌组织及淋巴结转移灶的表达,探讨Tiam11与胃癌侵袭及转移的关系.方法 应用免疫组化方法检测42例正常胃黏膜组织、53例不典型增生组织、86例胃癌及40例淋巴结转移灶中Tiam1蛋白的表达,分析其与胃癌临床病理因素间的关系.结果 Tiam1蛋白在正常胃黏膜组织中表达(11.9%)显著低于不典型增生组织(49.1%)、癌组织(83.7%)和淋巴结转移灶(90.0%),差异有显著性(P＜0.01),且随胃癌组织浸润深度的增加及伴有淋巴结转移,Tiam1蛋白阳性率逐渐升高,差异有显著性(P＜0.05或P＜0.01).但Tiam1蛋白表达水平与胃癌患者的性别、年龄及组织类型无关(P＞0.05).结论 随着胃癌的侵袭及转移,Tiam1表达呈上升趋势,与胃癌进展转移呈正相关.Tiam1基因有可能成为肿瘤治疗的新靶点.     

Expression of Tiam1 in lung cancer and its clinical significance

The aim of this study was to analyze T-cell lymphoma invasion and metastasis-inducing factor 1 (Tiam1) expression in lung cancer patients. A total of 204 patients with lung cancer tissue lesions were enrolled in the present study, along with 40 cases of normal lung tissue and 40 of normal fetal lung tissue. Tiam1 protein expression level was determined using intensity quantitative analysis, for comparison in lung cancer, metastatic, normal lung, and fetal lung tissue. The positive unit (PU) of Tiam1 was 13.5 ± 5.42 in lung cancer, 5.67 ± 1.56 in normal epithelial cells, and 5.89 ± 1.45 in fetal lung epithelial cells. The value in the lung cancer tissue was significantly higher than that in the normal lung tissue and the fetal lung tissue (P<0.01). The Tiam1 PU values with lymph node metastasis and without lymph node metastasis were 15.2 ± 4.34 and 12.5 ± 4.23, respectively, and the difference was statistically significant (P<0.05). The Tiam1 PU values in different tumor, nodes, metastasis (TNM) stages, III-IV period, and I-II phase were 14.7 ± 4.14 and 11.0 ± 5.34 (P <0.05). A correlation was found between Tiam1 expression and the age of patient, tumor size, tumor type, and tumor differentiation. Tiam1 protein expression in the lung tumor tissue is significantly higher than that in the normal lung tissue and fetal lung tissue. Tiam1 expression may be closely related to lung cancer development and metastasis.     

Prognostic relevance of Tiam1 protein expression in prostate carcinomas

The Rac-specific guanine nucleotide exchange factor, Tiam1, plays a major role in oncogenicity, tumour invasion and metastasis but its usefulness as a prognostic marker in human cancer has not been tested yet. In the present study, Tiam1 expression was analysed in benign secretory epithelium, pre-neoplastic high-grade prostatic intraepithelium neoplasia (HG-PIN) and prostate carcinomas of 60 R0-resected radical prostatectomy specimens by semiquantitative immunohistochemistry. Tiam1 proved significantly overexpressed in both HG-PIN (P<0.001) and prostate carcinomas (P<0.001) when compared to benign secretory epithelium. Strong Tiam1 overexpression (i.e. > or =3.5-fold) in prostate carcinomas relative to the respective benign prostatic epithelium was statistically significantly associated with disease recurrence (P=0.016), the presence of lymph vessel invasion (P=0.031) and high Gleason scores (GS) (i.e. > or =7) (P=0.044). Univariate analysis showed a statistically significant association of strong Tiam1 overexpression with decreased disease-free survival (DFS) (P=0.03). This prognostic effect of strong Tiam1 overexpression remained significant in multivariate analysis including preoperative prostate-specific antigen levels, pT stage, and GS (relative risk= 3.75, 95% confidence interval=1.06-13.16; P=0.04). Together, our data suggest that strong Tiam1 overexpression relative to the corresponding benign epithelial cells is a new and independent predictor of decreased DFS for patients with prostate cancer.     

T淋巴瘤侵袭转移诱导因子1与肿瘤侵袭转移的研究进展

T淋巴瘤侵袭转移诱导因子1(Tlymphoma invasion and metastasis inducing factor 1，Tiam 1)，是Rho样GTPase的GDP分离刺激因子，具有调节细胞骨架结构重组，促进细胞运动的功能。研究表明，Tiam1过表达可以诱导肿瘤细胞侵袭、转移，其分子生物学基础主要基于：Tiam1与肿瘤“细胞骨架-粘附分子-细胞外基质”跨膜系统的相互作用，Tiam1对肿瘤细胞增殖和凋亡的影响，以及其它肿瘤侵袭转移相关因子对Tiaml活性的调控几方面。同时，现有实验结果提示，Tiam1活性调节的多样性和生物效应的特异性，以及Tiam1与其他肿瘤侵袭转移相关因子间的关系及信号转导机制，尚有待深入研究。     

胃癌组织Tiam1和CD44V6及Ecadherin表达与分化程度相关性的研究

目的:探讨Tiam1、CD44V6和Ecadherin在胃癌组织中的表达及其与病理生物学行为的关系.方法:应用RT-PCR和SP法对56例胃癌和15例正常胃黏膜组织进行Tiam1、CD44V6和Ecadherin蛋白检测.结果:与正常胃黏膜组织相比,Tiam1和CD44V6在胃癌组织中高表达(χ2=32.92,P=0.000;χ2=5.63,P=0.018),Ecadherin在胃癌组织中低表达(χ2=10.99,P=0.001);胃癌组织Tiam1、CD44V6和Ecadherin的表达与组织分化程度密切相关(χ2=5.48,P=0.022;χ2=5.72,P=0.016;χ2=5.63,P=0.018);Spearman等级相关分析显示,Tiam1与CD44V6的表达呈正相关(rs=0.576,P=0.000),Tiam1与Ecadherin的表达呈负相关(rs=-0.428,P=0.001).结论:Tiam1、CD44V6和Ecadherin的表达与胃癌的发生、发展和分化程度密切相关.