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Clinical Significance of Circulating Tumor Cells and Lymph Node Micrometastases in Gastrointestinal cancer

循环肿瘤细胞和淋巴结微转移在胃肠道癌中的临床意义

基本信息

批准号：
19390339
负责人：
UENOSONO Yoshikazu
金额：
$ 12.31万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2007
资助国家：
日本
起止时间：
2007 至 2009
项目状态：
已结题

项目摘要

(1) Circulating tumor cells in blood detected by CellSearch System in gastric cancer The purposes of this study are to evaluate CTCs of peripheral blood (PB) and portal vein blood (PV) with gastric cancer patients using CellSearch System (CSS), and to investigate the relation of the recurrence. 【Methods】 In 50 patients with T1-3 gastric cancer, PB was collected 10ml before the gastrectomy, and PV was collected 10ml during operation. 【Results】CTCs were detected in 18% from PB, 24% from PV and 28% from PB and/or PV. CTCs were found in 8% with T1, 26% with T2, 44% with T3. Detection rate of CTCs were correlated with the results of Stage (p=0.007), vessel invasion (p=0.008), lymphatic invasion (p=0.007) and lymph node metastasis (p=0.01). The recurrences were detected in 11 patients (78.5%) with CTCs, and there was statistically significant difference in over all survival between patients with or without CTCs (p=0.0049). 【Conclusions】The identification of CTCs is very useful to follow up a … More fter operation and to perform the adjuvant chemotherapy in gastric cancer.(2)-1 The utility of rapid diagnosis of lymph node metastasis in gastric cancer using a multiplex real-time RT-PCR assayThe purpose of this study was to evaluate the utility of a prototype RT-PCR assay run on the SmartCycler^[○!R] that enables the rapid diagnosis of lymph node metastasis in gastric cancer within 40 minutes. The purpose of this study was to verify the utility of the SmartCycler^[○!R] as compared to conventional RT-PCR using the LightCycler^[○!R]. 【Patients and methods】47 overt metastatic lymph nodes from 8 patients with advanced gastric cancer and 22 benign lymph nodes from patients without malignant tumor who received surgery were obtained with informed consent. We examined the metastatic lymph nodes by RT-PCR using multiple markers using CEA and CK19 by the LightCycler^[○!R] and SmartCycler^[○!R]. 【Results】 In the singlex assay, the sensitivity of CEA and CK19 was 91.5% and 70.2% in the LightCycler^[○!R], and 97.9% and 95.7% in the prototype assay system, respectively. In the multiplex assay, the sensitivity was 91.5% in the LightCycler^[○!R] system and 97.9% in the SmartCycler^[○!R], respectively. 【Conclusion】Rapid diagnosis for lymph node metastasis using RT-PCR by the SmartCycler^[○!R] has equally high precision for detecting lymph node metastasis as the conventional LightCycler^[○!R]. In this study the SmartCycler^[○!R] is advantageous for the diagnosis of lymph node metastasis in gastric cancer when run with the prototype assay.(2)-2 Utility of the GeneSearch BLN Assay for Rapid Evaluation of Sentinel Lymph Nodes in Breast CancerOur goal was to evaluate the clinical application of the Breast Lymph Node (BLN) assay, a real-time RT-PCR assay for SLN metastases, by comparing this test with routine pathological examination. 【Methods】One hundred seventeen patients with breast cancer underwent breast surgery with SLN biopsy. Each SLN was cut in half along the plane of the longest dimension. Half of each node was examined by the BLN assay's 2 markers, mammaglobin (MG) and cytokeratin 19 (CK19), and the other half was examined by hematoxylin and eosin staining (HE) and immunohistochemical staining (IHC) for pancytokeratins. 【Results】A total of 204 SLNs were obtained from 117 patients. HE identified metastases in 31 SLNs (15.2%), and IHC detected metastases in 6 SLNs ; 40 SLNs from 32 patients were positive for metastasis by the BLN assay. The assay results correlated with the pathological diagnoses by HE and IHC (p<0.001). BLN Assay sensitivity compared with pathological findings classified according to TNM was 95.7% for macrometastases, 60.0% for micrometastases, and 55.6% for isolated tumor cells. 【Conclusion】The 2-marker BLN assay has performance comparable to, and analyzes more tissue than, routine pathological examination. Therefore, clinical intraoperative use of the BLN assay for SLNs may result in reduction of the second surgery for axillary lymph node dissections. Less

(1)CellSearch系统检测胃癌患者外周血中循环肿瘤细胞本研究的目的是应用CellSearch系统（CSS）检测胃癌患者外周血和门静脉血中循环肿瘤细胞（CTC），并探讨其与胃癌复发的关系。[方法] 50例T1-3期胃癌患者，术前采集PB 10 ml，术中采集PV 10 ml。[结果] 18%的外周血、24%的肺静脉、28%的外周血和/或肺静脉中检出CTCs。T1、T2、T3期CTCs检出率分别为8%、26%、44%。CTCs的检出率与肿瘤分期（p=0.007）、血管浸润（p=0.008）、淋巴管浸润（p=0.007）和淋巴结转移（p=0.01）相关。有11例（78.5%）CTC患者复发，有或无CTC患者的总生存率差异有统计学意义（p=0.0049）。[结论] CTCs的鉴定对临床随访有重要意义。 ...更多信息胃癌术后辅助化疗。(2)-1多重实时RT-PCR快速诊断胃癌淋巴结转移的实用性本研究的目的是评估在SmartCycler上运行的原型RT-PCR检测的实用性^[○！R]，能够在40分钟内快速诊断胃癌的淋巴结转移。本研究旨在验证SmartCycler^[○！R]与使用LightCycler^[○！R]。[患者与方法]收集8例进展期胃癌患者的47个显性转移淋巴结和22例非恶性肿瘤患者的良性淋巴结，均在知情同意的情况下进行手术。我们通过RT-PCR使用多种标记物使用CEA和CK 19通过LightCycler^[○！R]和SmartCycler^[○！R]。[结果]单次法检测CEA和CK 19的灵敏度分别为91.5%和70.2%。R]，在原型测定系统中分别为97.9%和95.7%。在多重检测中，LightCycler^[○！R]系统和SmartCycler^[○！R]，分别。[结论] SmartCycler应用RT-PCR快速诊断淋巴结转移^[○！R]在检测淋巴结转移方面具有与传统LightCycler^[○！R]。在本研究中，SmartCycler^[○！当用原型测定运行时，R]有利于胃癌中淋巴结转移的诊断。(2)-2 GeneSearch BLN检测在乳腺癌前哨淋巴结快速评估中的应用我们的目标是通过比较乳腺淋巴结（BLN）检测与常规病理检查，评估BLN检测（SLN转移的实时RT-PCR检测）的临床应用。[方法] 117例乳腺癌患者均行乳腺手术，并行SLN活检。将每个SLN沿最长尺寸的平面沿着切成两半。每个淋巴结的一半通过BLN检测的2种标记物，乳房珠蛋白（MG）和细胞角蛋白19（CK 19）进行检查，另一半通过苏木精和伊红染色（HE）和免疫组化染色（IHC）进行检查，以检测泛细胞角蛋白。[结果] 117例患者共获得SLN 204枚。HE检查发现31例SLN（15.2%）转移，IHC检查发现6例SLN转移; BLN检测发现32例患者的40例SLN转移阳性。检测结果与HE和IHC病理诊断结果相关（p<0.001）。与根据TNM分类的病理结果相比，BLN检测灵敏度对于大转移为95.7%，对于微转移为60.0%，对于分离的肿瘤细胞为55.6%。[结论]双标记BLN法与常规病理学检查方法相比，可分析更多的组织。因此，SLN的BLN检测的临床术中使用可能导致腋窝淋巴结清扫术的二次手术减少。少