Molecular staging of early colon cancer on the basis of sentinel node analysis: A multicenter phase II trial
Molecular staging of early colon cancer on the basis of sentinel node analysis: A multicenter phase II trial
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DOI：
10.1200/jco.2001.19.4.1128
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发表时间：
2001-02-15
影响因子：
45.3
通讯作者：
Hoon, DSB
中科院分区：
文献类型：
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作者：
Bilchik, AJ;Saha, S;Hoon, DSB
目的：大约30%的美国癌症联合委员会I期或II期结直肠癌（CRC）患者发展为全身性疾病。我们假设对原发性结直肠癌前哨淋巴结（SNs）的多标记逆转录聚合酶链反应（RT-PCR）分析可以检测到传统组织病理学分析无法检测到的微转移。患者和方法：在一项多机构研究中，40例原发性结直肠癌患者在结肠切除术时进行了染料定向淋巴定位。每个染色的SN被标记，肿瘤和区域淋巴结被整体切除。所有淋巴结行常规苏木精和伊红（HE）染色。此外，将每个SN切成多个切片进行细胞角蛋白免疫组化（CK-IHC）染色，RT-PCR和电化学发光检测三种标记物：β链人绒毛膜促性腺激素、肝细胞生长因子受体和通用黑色素瘤相关抗原。在可能的情况下，还对原发肿瘤组织进行RT-PCR检测。个体标记物的检测灵敏度为10(-3)~ 10（-4）杯RNA和10(7)个健康供体淋巴细胞中的1 ~ 5个肿瘤细胞。结果：每例患者可检出1 ~ 3例SNs。每个结直肠癌标本平均切除15个淋巴结。如果同一标本中所有标记的（前哨）淋巴结组织病理学均为肿瘤阴性，则没有非前哨（未标记）淋巴结含有肿瘤的证据。SNs HE染色发现肿瘤10例（25%），SNs CK-IHC检测发现隐匿性微转移4例（10%），SNs HE阴性。在其余26例没有HE或CK-IHC累及SN的患者中，12例（46%）的RT-PCR结果呈阳性。每个SN中表达的标志物数量与原发肿瘤的T分期相关（P < .04）。原发肿瘤与组织病理学阳性的各对（n = 38）的标记表达有79%的一致性，而RT-PCR阳性与组织病理学阳性的SNs之间有86%（14 / 12）的一致性。结论：鉴别和集中检查淋巴结是一种新的结直肠癌分期方法。CK-IHC和RT-PCR在53%的传统分期技术阴性的患者中发现了隐匿性微转移。这些SN的超灵敏检测可以识别出CRC复发风险较高的患者，因此更有可能从全身辅助治疗中获益。
Purpose: Approximately 30% of patients with American Joint Committee on Cancer stage I or II colorectal cancer (CRC) develop systemic disease. We hypothesized that multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of sentinel lymph nodes (SNs) draining a primary CRC could detect micrometastases not detected by conventional histopathologic analysis.Patients and Methods: In a multi-institutional study, 40 patients with primary CRC underwent dye-directed lymphatic mapping at the time of colon resection. Each dye-stained SN was tagged, and the tumor and regional nodes were resected en bloc. All lymph nodes were examined by conventional hematoxylin and eosin (HE) staining. In addition, each SN was cut into multiple sections for cytokeratin immunohistochemical (CK-IHC) staining and for RT-PCR and electrochemiluminescent detection of three markers: beta -chain human chorionic gonadotropin, hepatocyte growth factor receptor, and universal melanoma-associated antigen. Whenever possible, RT-PCR assay was also performed on primary tumor tissue. The detection sensitivity of individual markers was 10(-3) to 10(-4) mug of RNA and one to five tumor cells in 10(7) lymphocytes of healthy donors.Results: One to three SNs were identified in each patient. An average of 15 nodes were removed from each CRC specimen. No nonsentinel (untagged) node contained evidence of tumor if all tagged (sentinel) nodes in the same specimen were histopathology tumor-negative. HE staining of SNs identified tumor in 10 patients (25%), and CK-IHC of SNs identified occult micrometastases in four patients (10%) whose SNs were negative by HE. Of the remaining 26 patients with no evidence of SN involvement by HE or CK-IHC, 12 (46%) had positive RT-PCR results. The number of markers expressed in each SN correlated (P < .04) with the T stage of the primary tumor. There war 79% concordance in marker expression for the respective pairs (n = 38) of primary tumor and histopathologically positive SNs, and 86% (12 of 14) concordance between RT-PCR positive and histopathologically positive SNs.Conclusion: Identification and focused examination of the SN is a novel method of staging CRC. CK-IHC and RT-PCR identified occult micrometastases in 53% of patients whose SNs were negative by conventional staging techniques. These ultrasensitive assays of the SN can identify patients who may be at high risk for recurrence of CRC and therefore are more likely to benefit from systemic adjuvant therapy.