采用多标记逆转录-聚合酶链反应法对胃癌患者淋巴结微转移进行基因检测。

Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase-polymerase chain reaction assay.

作者信息

Okada Y, Fujiwara Y, Yamamoto H, Sugita Y, Yasuda T, Doki Y, Tamura S, Yano M, Shiozaki H, Matsuura N, Monden M

机构信息

Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Suita City, Osaka, Japan.

出版信息

Cancer. 2001 Oct 15;92(8):2056-64. doi: 10.1002/1097-0142(20011015)92:8<2056::aid-cncr1545>3.0.co;2-l.

DOI:10.1002/1097-0142(20011015)92:8<2056::aid-cncr1545>3.0.co;2-l

PMID:11596020

Abstract

BACKGROUND

Some patients with gastric carcinoma experience local disease recurrence despite undergoing curative resection of the tumor and regional lymph nodes (LNs), suggesting the presence of occult micrometastases. To evaluate the presence of gastric carcinoma micrometastasis in patients with otherwise histologically negative LNs, the authors established and tested a multiple-marker reverse transcriptase-polymerase chain reaction (RT-PCR) assay.

METHODS

The authors assessed 435 LNs from 28 patients with gastric carcinoma who underwent gastrectomy with lymphadenectomy using the multiple-marker RT-PCR assay in addition to histologic examination. Carcinoembryonic antigen (CEA), cytokeratin-20 (CK-20), and MAGE-3 gene markers were used in this assay. LNs were scored positive for metastasis if at least one marker was positive. The presence of LN micrometastases also was verified by immunohistochemistry in histologically negative and RT-PCR positive LNs.

RESULTS

Sixty-nine of 435 LNs (16%) were positive for CEA (12%), CK-20 (10%), or MAGE-3 (5%). None of 16 control LNs obtained from disease free patients was positive by RT-PCR assay. Of 414 histologically negative LNs, 50 LNs (12%) were scored as positive for metastasis by the assay. Of 26 patients who underwent curative resection, the disease stage was upgraded in 10 patients by genetic diagnosis (from Stage IA to Stage IB in 5 patients, from Stage IB to Stage IIIA in 2 patients, from Stage IB to Stage IV in 1 patient, from Stage IB to Stage II in 1 patient, and from Stage II to Stage IIIB in 1 patient). In the latter 10 patients, immunohistochemistry identified LN micrometastases in 4 patients. Two patients with micrometastasis by genetic diagnosis had recurrent disease within 1 year.

CONCLUSIONS

The current results indicate that the multiple-marker RT-PCR assay is a useful tool for the detection of micrometastases in regional LNs in patients with gastric carcinoma and may improve the staging system of gastric carcinoma for these patients.

摘要

背景

一些胃癌患者尽管接受了肿瘤及区域淋巴结（LN）的根治性切除，但仍出现局部疾病复发，提示存在隐匿性微转移。为评估组织学检查时LN为阴性的胃癌患者中微转移的存在情况，作者建立并测试了一种多标记逆转录聚合酶链反应（RT-PCR）检测方法。

方法

作者对28例行胃癌根治术及淋巴结清扫术患者的435个LN进行评估，除组织学检查外，还使用多标记RT-PCR检测方法。该检测方法使用癌胚抗原（CEA）、细胞角蛋白-20（CK-20）和MAGE-3基因标记物。如果至少一个标记物呈阳性，则LN转移评分为阳性。通过免疫组织化学在组织学阴性且RT-PCR阳性的LN中验证LN微转移的存在。

结果

435个LN中的69个（16%）CEA（12%）、CK-20（10%）或MAGE-3（5%）呈阳性。从无病患者获得的16个对照LN通过RT-PCR检测均为阴性。在414个组织学阴性的LN中，50个LN（12%）通过该检测转移评分为阳性。在26例行根治性切除的患者中，10例患者的疾病分期通过基因诊断得到升级（5例从IA期升至IB期，2例从IB期升至IIIA期，1例从IB期升至IV期，1例从IB期升至II期，1例从II期升至IIIB期）。在这10例患者中，免疫组织化学在4例患者中鉴定出LN微转移。2例基因诊断为微转移的患者在1年内出现疾病复发。