Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients
Limitations of specific reverse-transcriptase polymerase chain reaction markers in the detection of metastases in the lymph nodes and blood of breast cancer patients
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DOI：
10.1200/jco.1998.16.8.2632
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发表时间：
1998-08-01
影响因子：
45.3
通讯作者：
Hoon, DSB
中科院分区：
文献类型：
--
作者：
Bostick, PJ;Chatterjee, S;Hoon, DSB
目的：本研究通过逆转录聚合酶链反应（RT-PCR）和Southern印迹分析乳腺癌患者的前哨淋巴结（SN）和血液来评估特异性mRNA标记物检测微转移的潜力。我们评估了癌胚抗原（CEA）、细胞角蛋白-19（CK-19）、CK-20、通过RT-PCR测定健康供体（n = 13）的血液和来自非癌症患者（n = 3）的淋巴结中的胃肠道肿瘤相关抗原-733.2（GA 733.2）和粘蛋白-1（MUC-1）。在乳腺癌细胞系（n = 4）、原发性乳腺肿瘤（n = 8）和来自22名患有美国癌症联合委员会（AJCC）I至IIIA期乳腺癌的患者的SN（n = 22）的冷冻切片中评估靶mRNA标记物的RT-PCR测定的灵敏度。CK-20是唯一未在非癌症患者的淋巴结或血液中检测到的mRNA标记物。无癌患者的血液和淋巴结均表达CEA、CK-19、GA 733.2和MUG-I mRNA。所有四种乳腺癌细胞系和八种原发性乳腺肿瘤中的六种表达所有五种mRNA标记物。在常规组织病理学检查无转移的冷冻切片SN（n = 12）中，通过RT-PCR测定的mRNA表达范围为8%（CK-20）至92%（GA 733.2）。结论：CEA、CK-19、GA 733.2和MUC-1在非肿瘤患者的血液和淋巴结中均有表达，作为RT-PCR检测SNs微转移的mRNA标记物无诊断价值。需要进一步的研究来评估CK-20在乳腺癌患者的血液和冷冻切片SN中通过RT-PCR测定检测微转移的灵敏度，J Clin Oncol 16：2632-2640。(C)1998年，美国临床肿瘤学会。
Purpose: This study was performed to evaluate the potential of specific mRNA markers to detect micrometastases by reverse-transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis of sentinel lymph nodes (SNs) and blood from patients with breast cancer.Patients and Methods: We assessed the specificity of carcinoembryonic antigen (CEA), cytokeratin-19 (CK-19), CK-20, gastrointestinal tumor-associated antigen-733.2 (GA733.2), and mucin-1 (MUC-1) in the blood of healthy donors (n = 13) and lymph nodes from patients without cancer (n = 3) by RT-PCR assay. The sensitivity of the RT-PCR assay for the target mRNA markers was assessed in breast cancer cell lines (n = 4), primary breast tumors (n = 8), and the frozen sections of SNs (n = 22) from 22 patients with American Joint Committee on Cancer (AJCC) stages I to IIIA breast cancer.Results: CK-20 was the only mRNA marker not detected in lymph nodes or blood from patients without cancer. Both the blood and lymph nodes from patients without cancer expressed CEA, CK-19, GA733.2, and MUG-I mRNA, All four breast cancer cell lined and six of eight primary breast tumors expressed all five mRNA markers. Expression of mRNA by the RT-PCR assay in the frozen-section SNs (n = 12) without metastases by conventional histopathology ranged from 8% (CK-20) to 92% (GA733.2). Detection of RT-PCR cDNA products in frozen-section SNs war increased with Southern blot analysis compared with ethidium bromide gel electrophoresis (EtBr) for all mRNA markers except CK-19.Conclusion: CEA,CK-19, GA733.2, and MUC-1 show no diagnostic value as mRNA markers for the detection of micrometastases by the RT-PCR assay because they are expressed in the blood and lymph nodes of patients without cancer. Further studies are needed to assess the sensitivity of CK-20 to detect micrometastases by the RT-PCR assay in the blood and frozen-section SNs of patients with breast cancer, J Clin Oncol 16:2632-2640. (C) 1998 by American Society of Clinical Oncology.