淋巴结中GUCY2C表达与pN0期结直肠癌复发时间和无病生存期的关系
Association of GUCY2C expression in lymph nodes with time to recurrence and disease-free survival in pN0 colorectal cancer.
作者信息
Waldman Scott A, Hyslop Terry, Schulz Stephanie, Barkun Alan, Nielsen Karl, Haaf Janis, Bonaccorso Christine, Li Yanyan, Weinberg David S
机构信息
Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, 132 S 10th St, Philadelphia, PA 19107, USA.
出版信息
JAMA. 2009 Feb 18;301(7):745-52. doi: 10.1001/jama.2009.141.
CONTEXT
The established relationship between lymph node metastasis and prognosis in colorectal cancer suggests that recurrence in 25% of patients with lymph nodes free of tumor cells by histopathology (pN0) reflects the presence of occult metastases. Guanylyl cyclase 2C (GUCY2C) is a marker expressed by colorectal tumors that could reveal occult metastases in lymph nodes and better estimate recurrence risk.
OBJECTIVE
To examine the association of occult lymph node metastases detected by quantifying GUCY2C messenger RNA, using the reverse transcriptase-polymerase chain reaction, with recurrence and survival in patients with colorectal cancer.
DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 257 patients with pN0 colorectal cancer enrolled between March 2002 and June 2007 at 9 US and Canadian centers (7 academic medical centers and 2 community hospitals) provided 2570 fresh lymph nodes measuring 5 mm or larger for histopathology and GUCY2C messenger RNA analysis. Patients were followed up for a median of 24 months (range, 2-63 months) for disease recurrence or death.
MAIN OUTCOME MEASURES
Time to recurrence (primary outcome) and disease-free survival (secondary outcome) relative to expression of GUCY2C in lymph nodes.
RESULTS
Thirty-two patients (12.5%) had lymph nodes negative for GUCY2C (pN0 [mol-]), and all but 2 remained free of disease during follow-up (recurrence rate, 6.3%; 95% confidence interval [CI], 0.8%-20.8%). Conversely, 225 patients (87.5%) had lymph nodes positive for GUCY2C (pN0 [mol+]), and 47 developed recurrent disease (20.9%; 95% CI, 15.8%-26.8%) (P = .006). Multivariate analyses revealed that GUCY2C in lymph nodes was an independent marker of prognosis. Patients who were pN0 (mol+) exhibited earlier time to recurrence (adjusted hazard ratio, 4.66; 95% CI, 1.11-19.57; P = .04) and reduced disease-free survival (adjusted hazard ratio, 3.27; 95% CI, 1.15-9.29; P = .03).
CONCLUSION
Expression of GUCY2C in histologically negative lymph nodes appears to be independently associated with time to recurrence and disease-free survival in patients with pN0 colorectal cancer.
背景
结直肠癌中已确立的淋巴结转移与预后之间的关系表明，在组织病理学检查中淋巴结无肿瘤细胞（pN0）的患者中有25%出现复发，这反映了隐匿性转移的存在。鸟苷酸环化酶2C（GUCY2C）是一种由结直肠癌肿瘤表达的标志物，它可以揭示淋巴结中的隐匿性转移，并更好地估计复发风险。
目的
通过逆转录聚合酶链反应定量检测GUCY2C信使核糖核酸来检测隐匿性淋巴结转移，并探讨其与结直肠癌患者复发及生存的关系。
设计、地点和参与者：对2002年3月至2007年6月期间在美国和加拿大9个中心（7个学术医疗中心和2个社区医院）入组的257例pN0结直肠癌患者进行前瞻性研究，提供了2570个直径5毫米或更大的新鲜淋巴结用于组织病理学和GUCY2C信使核糖核酸分析。对患者进行了为期24个月（范围2 - 63个月）的随访，以观察疾病复发或死亡情况。
主要观察指标
相对于淋巴结中GUCY2C的表达，复发时间（主要观察指标）和无病生存期（次要观察指标）。
结果
32例患者（12.5%）的淋巴结GUCY2C呈阴性（pN0[mol-]），除2例患者外，其余患者在随访期间均未出现疾病复发（复发率为6.3%；95%置信区间[CI]，0.8% - 20.8%）。相反，225例患者（87.5%）的淋巴结GUCY2C呈阳性（pN0[mol+]），其中47例出现疾病复发（20.9%；95%CI，15.8% - 26.8%）（P = 0.006）。多因素分析显示，淋巴结中的GUCY2C是一个独立的预后标志物。pN0（mol+）的患者复发时间更早（调整后风险比为4.66；95%CI，1.11 - 19.57；P = 0.04），无病生存期缩短（调整后风险比为3.27；95%CI，1.15 - 9.29；P = 0.03）。
结论
在组织学检查为阴性的淋巴结中，GUCY2C的表达似乎与pN0结直肠癌患者的复发时间和无病生存期独立相关。
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