检测pT_(1-4a)N_(1-3)M_0期胃癌淋巴结微转移检测的临床意义

目的:探讨胃癌淋巴结微转移及临床病理因素对p T1-4aN1-3M0期胃癌患者术后5年无瘤生存率的影响。方法:选取我院2009年1月至12月期间胃肠外科单一手术组行D2胃癌根治术p T1-4aN1-3M0期患者63例1427枚HE染色阴性淋巴结,应用免疫组化法检测这些淋巴结中CK19表达,观察微转移的情况并分析发生微转移的胃癌患者临床病理特征及对患者5年无瘤生存率的影响。结果:临床病理分期p T1-4aN1-3M0胃癌患者中,经免疫组化染色,1427枚HE常规染色阴性淋巴结中CK19阳性表达率为15.49%(221/1427);63例胃癌患者中CK19表达阳性率39.68%(25/63);术后随访时间5.6~68.5月(平均时间43.88月),淋巴结中CK19阴性表达、阳性表达患者的总5年生存率分别为52.63%、28.00%;两者无瘤生存率差异有统计学意义(x2=8.677,P=0.003)。淋巴结CK19阳性表达与胃癌患者的肿瘤直径(P0.05)、浸润胃壁深度(P0.05)有关。COX生存回归分析显示淋巴结微转移为独立预后因素。25例患者发现淋巴结微转移并推荐再分期,再分期率39.68%(25/63)。结论:p T1-4aN1-3M0期胃癌病人,CK-19免疫组化法染色能检出常规HE染色阴性淋巴结中的微转移,有助于细化分期、判断预后及指导治疗。     

MMP2和MMP9在粘膜内胃癌中表达及其临床病理意义

目的:观察基质金属蛋白酶(MMP)家族成员MMP2和MMP9在粘膜内胃癌中的表达及其与淋巴结转移的相关性。方法:研究病例为病理诊断为粘膜内胃癌的档案病例,应用免疫组织化学技术检测MMP2和MMP9在粘膜内胃癌中表达的临床病理意义,特别是与淋巴结转移的相关性。结果:临床病理分析结果显示有淋巴结转移的IMGC病例肿块直径要显著大于无淋巴结转移的IMGC。有淋巴结转移IMGC中低分化腺癌发生率要显著高于无淋巴结转移组。有淋巴结转移IMGC中淋巴管侵犯发生率要显著高于无淋巴结转移组。免疫组化结果显示,MMP2在正常胃粘膜上皮和粘膜内胃癌中的阳性表达率分别是7%和43.93%,有显著性差异(P0.01),MMP9在正常胃粘膜上皮和粘膜内胃癌中的阳性表达率分别为和23%和48.48%,无显著性差异(P0.05)。MMP9在淋巴结转移组中的阳性率(87.5%)显著高于无淋巴结转移组(36%),在有淋巴管侵犯病例中的表达率(83.3%)显著高于无淋巴管侵犯的病例(30%),差异均有统计意义(P0.05);而MMP2的表达与有无淋巴结转移及淋巴管侵犯均无显著相关性(P0.05)。结论:MMP9可能作为预测粘膜内胃癌是否有淋巴结转移的标志物,但需要结合组织分化、肿块大小和淋巴管侵犯等临床病理特点综合判断。MMP2可能与粘膜内胃癌的发生有关而作为早期诊断的指标。     

幽门螺杆菌感染与胃癌侵袭转移及COX-2和MMP-9表达的关系

目的:探讨COX-2和MMP-9在胃癌组织中的表达及其与幽门螺杆菌感染和胃部转移侵袭的关系.方法:采用快速尿素酶试验及Warthin-Starry银染色法检测45例胃癌标本中幽门螺杆菌感染情况,采用免疫组织化学法检测COX-2和MMP-9在胃癌组织中的表达,对其与幽门螺杆菌感染和胃癌患者临床病理特征的相关性进行分析.结果:①幽门螺杆菌感染组胃癌中浆膜侵袭和淋巴结转移卒均高于无幽门螺杆菌感染组(P<0.05).②胃癌浆膜侵袭组和淋巴结转移组中COX-2、MMP-9蛋白表达阳性率均分别显著高于无胃癌浆膜侵袭组、淋巴结转移组(P<0.05).③幽门螺杆菌感染与COX-2和MMP-9表达具有相关性.结论:幽门 螺杆菌感染能够增加胃癌的侵袭转移能力,其机制可能与COX-2和MMP-9表达增加有关.     

EMT标志分子Vimentin在胃癌中的表达和临床意义

目的:探讨EMT标志分子Vimentin在胃癌中的表达和临床意义。方法:利用免疫组化染色的方法检测Vimentin在120例胃癌及其相应癌旁组织中的表达,统计分析Vimentin的表达水平与年龄、性别、组织学类型、TNM分期、淋巴结转移等临床病理特征间的相关性。结果:Vimentin在胃癌中的表达阳性率为55.8%,远高于相应癌旁组织的22.5%(P0.01),进一步分析研究发现Vimentin的表达水平在Ⅲ和Ⅳ期的胃癌中(TNM分期)的表达明显高于Ⅰ和Ⅱ期的胃癌,差异具有统计学意义(P=0.009),在发生淋巴结转移胃癌中表达明显高于未发生淋巴结转移的胃癌,差异具有统计学意义(P0.000)。结论:Vimentin在胃癌中高表达,其表达水平与TNM分期、淋巴结转移密切相关,提示Vimentin在胃癌的转移过程中可能发挥重要作用。     

VEGF-C 和VEGFR-3 在胃癌组织中的表达及临床意义

目的:探讨胃癌患者血管内皮生长因子C(vascular endothelial growth factor-C,VEGF-C及血管内皮生长因子受体-3(vascular endothelial growth factor receptor-3,VEGFR-3)在胃癌组织中的表达,从而确定胃癌预后的分子标志物。方法:搜集整理临床资料,采用Real-time PCR及ELISA法检测43例胃癌组织VEGF-C和VEGFR-3的表达。结果:43例胃癌组织中均有不同程度的VEGF-C和VEGFR-3的表达,Real-time PCR结果显示胃癌组织淋巴结转移组和非转移组VEGF-C和VEGFR-3的表达分别为0.07±0.01和0.12±0.01,0.03±0.01和0.06±0.02,与正常对照组相比,差异有显著性(p<0.05)。ELISA检测显示,与正常胃组织中VEGF-C和VEGFR-3的蛋白表达相比,胃癌无淋巴结转移组及胃癌并发淋巴结转移组中VEGF-C和VEGFR-3均明显增加。结论:VEGF-C和VEGFR-3的表达与胃癌淋巴结转移密切相关,提示胃癌标本VEGF-C和VEGFR-3的检测可作为胃癌预后的分子标志物。     

VEGF-C和VEGFR-3在胃癌组织中的表达及临床意义

目的：探讨胃癌患者血管内皮生长因子C（vascular endothelial growth factor-C,VEGF-C及血管内皮生长因子受体-3（vascular endothelial growth factor receptor-3,VEGFR-3）在胃癌组织中的表达,从而确定胃癌预后的分子标志物。方法：搜集整理临床资料,采用Real-time PCR及ELISA法检测43例胃癌组织VEGF-C和VEGFR-3的表达。结果：43例胃癌组织中均有不同程度的VEGF-C和VEGFR-3的表达,Real-time PCR结果显示胃癌组织淋巴结转移组和非转移组VEGF-C和VEGFR-3的表达分别为0.07±0.01和0.12±0.01,0.03±0.01和0.06±0.02,与正常对照组相比,差异有显著性（p〈0.05）。ELISA检测显示,与正常胃组织中VEGF-C和VEGFR-3的蛋白表达相比,胃癌无淋巴结转移组及胃癌并发淋巴结转移组中VEGF-C和VEGFR-3均明显增加。结论：VEGF-C和VEGFR-3的表达与胃癌淋巴结转移密切相关,提示胃癌标本VEGF-C和VEGFR-3的检测可作为胃癌预后的分子标志物。     

DOK2对胃癌细胞生物学行为的影响及其与胃癌预后的关系

构建重组质粒pc DNA3.1-DOK2并转染胃癌细胞BGC823,采用平板集落形成、CCK8法和软琼脂克隆形成实验检测过表达DOK2基因对BGC823生物学行为的影响,并采用免疫组织化学法检测116例胃癌组织中DOK2蛋白的表达,分析其与胃癌临床病理学特征及预后的关系。结果显示,过表达的DOK2基因对BGC823细胞增殖有显著抑制作用。在所有胃癌组织中,DOK2蛋白低表达占62.93%,且其与胃癌浸润深度、淋巴结转移以及分化程度密切相关;DOK2蛋白的表达、胃癌浸润深度、淋巴结转移、远处转移以及分化程度是影响患者预后生存时间的重要因素。     

前哨淋巴结检测方法及其在肿瘤中的研究进展

前哨淋巴结(sentinel lymph node,SLN)是肿瘤淋巴结转移的第一站,SLN活检肿瘤阳性的患者需要做系统性淋巴结清扫;SLN活检阴性的患者,不需要做系统性淋巴结清扫,可以缩短手术时间,降低手术费用,减少手术并发症;目前识别SLN的方法包括生物活性染料示踪法,放射性核素示踪法,联合示踪法,纳米炭(carbon nanoparticles,CNP)标记前哨淋巴结活检技术以及吲哚菁绿(Indocyanine Green,ICG)荧光标记法。SLN活检技术在乳腺癌、甲状腺癌、胃癌、恶性黑色素瘤、宫颈癌、子宫内膜癌等肿瘤中皆有不同程度的研究。本文通过复习文献,对前哨淋巴结检测方法予以归纳及其在常见肿瘤中的研究进展予以综述,旨在为恶性肿瘤临床治疗提供参考。     

胃癌原发灶及淋巴结Her2 基因表达的差异性研究

目的:明确胃癌原发灶与其转移淋巴结中Her2过表达或扩增的差异性,为临床胃癌治疗方案的选择提供参考依据。方法:选择112例经术后病理检查证实为胃癌原发灶Her2强阳性(Her2阳性表达为3+)表达并伴有淋巴结转移的患者样本,应用免疫组化方法并参照《胃癌Her2检测指南》中规定的检测流程重新判定有Her2过表达或扩增的胃癌原发病灶其相应的转移淋巴结中Her2有无过表达或扩增,再将检测结果进行比较。结果:112例患者中,胃癌组织Her2的阳性率为74.11%,淋巴结Her2的阳性表达为66.07%,二者共同阳性表达率为61.61%,差异无统计学意义(P=0.064)。两,二者一致率为83.04%,kappa检验结果为(Z=6.452,P0.001)。胃癌组织Her2的基因表达与年龄、性别、肿瘤位置和肿瘤大小以及远端转移均无显著相关性,而与Lauren分型、组织学分级、浸润深度、淋巴结转移以及TNM分期有关(P0.05)。结论:胃癌原发病灶中Her2过表达或扩增与其相应的转移淋巴结中Her2过表达或扩增具有一致性。胃癌组织Her2状态与Lauren分型、组织学分级、浸润深度、淋巴结转移以及TNM分期有关。     

胃癌血清Periostin、E-cadherine水平的研究

目的：通过检测并分析胃癌患者血清Periostin、E-cadherine水平与胃癌临床病理参数的关系以评价两者对胃癌的临床应用价值。方法：应用固相夹心酶联免疫吸附实验（Elisa）检测54例胃良性疾病患者对照组和128例胃癌患者（胃癌组）血清Periostin、E-cadherine水平。结果：胃癌组血清Periostin[（409.429±154.851）pg/ml]、E-cadherine[（38.834±11.676）ng/ml]水平均显著高于对照组,差异有显著统计学意义（P〈0.05）。胃癌根除组,有淋巴结转移组血清E-cadherine水平显著高于无淋巴结转移组,差异有统计学意义（P〈0.05）;血清Periostin水平随淋巴结转移个数的增多而升高,多重比较不同淋巴结转移个数分组差异有统计学意义（P〈0.05）;血清Periostin、E-cadherine水平随着胃癌浸润程度加深而升高,多重比较差异有统计学意义（P〈0.05）。胃癌组,有远处器官转移组患者血清Periostin水平[（505.617±163.950）pg/ml]、E-cadherine[（48.705±8.067）ng/ml]均明显高于无远处转移组,差别有显著统计学意义（P〈0.05）。胃癌组血清Periostin水平和血清E-cadherine水平呈低度正相关性。结论：血清Periostin、E-cadherine水平与胃癌的临床病理参数密切关系,对评价胃癌进展程度及预后有一定临床意义。     

The clinical importance of micrometastases within the lymphatic system in patients after total gastrectomy

Background

In spite of radical gastrectomy with resection of the lymphatic system, where no metastases are found during histopathological examination, about 30% of patients have relapse of the neoplastic process. This situation may be caused by micrometastases or isolated neoplastic cells in the lymphatic system which were not identified during a standard histopathological examination.

Aim

The aim of the study was to evaluate the clinical importance of micrometastases within the lymphatic system in patients with gastric cancer.

Materials and methods

A group of 20 patients treated for gastric cancer were subjected to retrospective analysis. Of all the patients who underwent surgery, a group with tumours classified as T1 or T2 was selected. No metastases within the lymphatic system were found in the standard evaluation – N0 mark. Paraffin-embedded blocks of lymph nodes were cut and new specimens were made, which were then stained again by means of immunohistochemistry. Antibodies against cytokeratin AE1/AE3 were used.

Results

A total of 319 lymph nodes were assessed in 20 patients in an H + E examination. After the immunohistochemical examination, micrometastases within the lymphatic system were found in 4 (20%) patients and isolated neoplastic cells in other 4 (20%) patients.

Conclusion

On the basis of numerous publications and our own material, we think that the presence of micrometastases may be related to a worse prognosis. The clinical importance of micrometastases within the lymphatic system in patients after total gastrectomy.     

Demonstration of mucinous-like carcinoma-associated antigen in bone marrow and lymph node biopsies from patients with breast carcinoma.

Two hundred and fifty bone marrow and 140 lymph nodal biopsies were analyzed immunocytochemically, using a mouse monoclonal antibody b-12 (M Ab b-12), which reacts with MCA (mucinous-like carcinoma-associated antigen). The presence of MCA in bone marrow specimens was demonstrated in 102 out of 105 (97.1%) breast cancer metastases, 5 out of 8 (62.5%) gastric cancers, 5 out of 6 (83.3%) colon cancers, 3 out of 5 (60%) prostate cancers, 11 out of 26 (42.3%) lung cancers and 25 out of 30 (83.3%) unknown primary cancers, while no positivity to anti-MCA antibody was found in 30 cases of normal bone marrow biopsies, 5 cases of non epithelial malignancies and 30 cases of hemolymphoproliferative disease. Normal lymph nodes and non-epithelial lymph node metastases did not show any reaction to M Ab b-12; on the contrary MCA positive staining was observed in 75 out of 75 (100%) lymph nodal metastases in breast cancer. These results suggest that application of M Ab b-12 in immunohistochemistry is valid for the detection of bone marrow and lymph nodal micrometastases of epithelial origin.     

Mesothelioma and asbestosis in a young woman following occupational asbestos exposure: Short latency and long survival: Case Report

Background

Occult neoplastic cells (ONCs) are the tumor cells floating in the lymph node sinuses, distant from the primary tumor, and supposed to be one of most reliable marker of prognosis.

Methods

We report here the case of a 52-year-old woman with a gastric cancer associated by numerous ONCs.

Results

Postoperative examination of the stomach disclosed an advanced, poorly differentiated adenocarcinoma with frequent lymph node metastases. In addition to ONCs and occasional micrometastases, focal aggregates of ONCs, one of the possible intermediate lesions between the ONCs and the usual metastases, are also observed.

Conclusions

In the present case, at least some of ONCs seem to form the microaggregates of tumor cells in lymph nodes, anchor in the sinuses, and grow up to the large tumorous lesion. Even if most of the ONCs were trapped and disappeared under the influence of tumor immunity, the detection of ONCs could be one of the reliable clues to estimate the prognosis.     

结直肠癌淋巴结微转移灶的临床病理研究

摘要目的：探讨结直肠癌淋巴结微转移灶的特点及其临床病理意义。方法：对我院2001年1月-2006年10月收治的56例无组织学淋巴结转移的结直肠癌患者的650个淋巴结进行微转移灶的免疫组织化学和组织学检测,并分析微转移灶与患者临床病理特征之间的关系。结果-通过对41,zm厚淋巴结连续切片进行观察,连续切片五片的微转移灶检出率较一片和两片的的微转移灶检出率显著升高（P〈0．05）。按解剖部位分组的患者微转移灶阳性率1组有66．67％（16／24）,2组有60％（9／15）,3组有41．2％（7／17）,无显著性差别（P〉0．05）。微转移灶与无组织学淋巴结转移的结直肠癌患者的肿瘤浸润深度（P=0．013）和肿块大小（P=0．037）存在显著性相关,但有微转移灶和无微转移灶的无组织学淋巴结转移的结直肠癌患者总体生存状况比较无显著差异（P〉0．05）。结论：微转移灶在无组织学淋巴结转移的结直肠癌淋巴结中较常见,与肿瘤大小和浸润深度有关,但与患者的预后无显著相关性。     

CEA mRNA在大肠癌患者微转移早期预测中的意义

目的:大肠癌是最常见的恶性肿瘤之一,血行转移是大肠癌根治性手术失败的原因之一,在根治性切除肿瘤患者中,有大部分患者死于肿瘤的复发和转移,因此早期发现大肠癌微转移,对于延长患者预后指导下一步治疗具有重要意义。本研究已检测大肠癌患者外周血和引流静脉血中CEA mRNA的表达,以探索手术操作和微转移的关系,以及引流静脉血中微转移的发生与临床病理因素的关系,探讨早期发现大肠癌血循环微转移的意义。方法:应用逆转录多聚酶链式反应(RT-PCR)法检测大肠癌患者手术前,手术后外周血及引流静脉血液中的CEA mRNA水平。结果:(1)大肠癌患者术前外周血CEA mRNA阳性率26.7%(16/60),引流静脉血阳性率48.3%(29/60),引流静脉血明显高于外周静脉血(P0.05)。(2)大肠癌引流静脉血中CEA mRNA在肿瘤大于5厘米者、Dukes C期、中低分化程度、有淋巴转移者、浸及浆膜者比外周静脉血更有统计学上的意义。(3)手术前后引流静脉血CEAm RNA阳性率具有显著差异(P0.05),外周血CEA mRNA阳性率无显著差异。结论:大肠癌引流静脉血微转移是大肠癌肝转移的发生的早期阶段,引流静脉血CEA mRNA的表达能更早期反映出大肠癌患者微转移的发生,引流静脉微转移发生率与肿瘤分化程度、浸润深度、TNM分期、淋巴结转移、远处转移相关,是反映大肠癌生物学行为的指标之一,手术对大肠癌血循环微转移有促进作用。     

CEAmRNA在大肠癌患者微转移早期预测中的意义

目的：大肠癌是最常见的恶性肿瘤之一,血行转移是大肠癌根治性手术失败的原因之一,在根治性切除肿瘤患者中,有大部分患者死于肿瘤的复发和转移,因此早期发现大肠癌微转移,对于延长患者预后指导下一步治疗具有重要意义。本研究已检测大肠癌患者外周血和引流静脉血中CEAmRNA的表达,以探索手术操作和微转移的关系,以及引流静脉血中微转移的发生与临床病理因素的关系,探讨早期发现大肠癌血循环微转移的意义。方法：应用逆转录多聚酶链式反应（RT-PCR）法检测大肠癌患者手术前,手术后外周血及引流静脉血液中的CEAmRNA水平。结果：（1）大肠癌患者术前外周血CEAmRNA阳性率26．7％（16／60）,引流静脉血阳性率48.3％（29／60）,引流静脉血明显高于外周静脉血（P〈0．05）。（2）大肠癌引流静脉血中CEAmRNA在肿瘤大于5厘米者、DukesC期、中低分化程度、有淋巴转移者、浸及浆膜者比外周静脉血更有统计学上的意义。（3）手术前后引流静脉血CEAmRNA阳性率具有显著差异（P〈O．05）,外周血CEAmRNA阳性率无显著差异。结论：大肠癌引流静脉血微转移是大肠癌肝转移的发生的早期阶段,引流静脉血CEAmRNA的表达能更早期反映出大肠癌患者微转移的发生,引流静脉微转移发生率与肿瘤分化程度、浸润深度、TNM分期、淋巴结转移、远处转移相关,是反映大肠癌生物学行为的指标之一,手术对大肠癌血循环微转移有促进作用。     

磁共振靶向对比剂在淋巴结成像中的研究进展

准确评价淋巴结转移与否关系到对肿瘤患者的分期和预后的判断。目前对淋巴结良恶性诊断的主要依据为淋巴结的大小和形态,正常大小的转移性淋巴结很可能被遗漏,增大的淋巴结是良性增生还是恶性转移也很难鉴别。近年来随着MR特异性对比剂,特别是MR靶向淋巴结对比剂的发展,MR淋巴成像（MR Lymphography,MRL）显示了极为诱人的前景。该文主要介绍MR淋巴靶向对比剂的研究进展。     

Epigenetic silencing of olfactomedin-4 enhances gastric cancer cell invasion via activation of focal adhesion kinase signaling

Downregulation of olfactomedin-4 (OLFM4) is associated with tumor progression, lymph node invasion and metastases. However, whether or not downregulation of OLFM4 is associated with epigenetic silencing remains unknown. In this study, we investigate the role of OLFM4 in gastric cancer cell invasion. We confirm the previous result that OLFM4 expression is increased in gastric cancer tissues and decreases with an increasing number of metastatic lymph nodes, which are associated with OLFM4 promoter hypermethylation. Overexpression of OLFM4 in gastric cancer cells had an inhibitory effect on cell invasion. Furthermore, we found that focal adhesion kinase (FAK) was negatively correlated with OLFM4 in regards to lymph node metastasis in gastric cancer tissues. Also, inhibition of FAK induced by OLFM4 knockdown resulted in a decrease in cell invasion. Thus, our study demonstrates that epigenetic silencing of OLFM4 enhances gastric cancer cell invasion via activation of FAK signaling. [BMB Reports 2015; 48(11): 630-635]     

Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases.

The bone marrow of 307 patients with primary breast cancer was examined for tumour cells by immunocytochemistry using an antiserum to epithelial membrane antigen. Micrometastases were found in 81 cases (26.4%) and their presence was related to various poor prognostic factors: spread to lymph nodes, vascular invasion, T stage, and pathological size. The median duration of follow up was 28 months. Seventy five patients relapsed, 60 at distant sites. Of these 60 patients, 26 had micrometastases detected at presentation and 34 were free of micrometastases initially. The relapse free interval was significantly shorter for patients with micrometastases, and these patients had a shorter survival. Analysis of the sites of relapse showed that the test predicted bone metastases only. Thus 10 out of 19 patients (53%) who developed bone metastases at first relapse had micrometastases at presentation compared with only 41 out of 288 patients (14%) who remained free of bone metastases or relapsed in non-skeletal sites. The presence of micrometastases detected at the time of initial surgery in a patient with primary breast cancer is a useful predictor of early relapse in bone and may help in selecting patients for subsequent systemic treatment.