Conzelmann Michael, Dieterle Christoph P, Linnemann Ulrich, Berger Martin R
Unit of Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg, Germany.
Int J Cancer. 2003 Nov 20;107(4):617-28. doi: 10.1002/ijc.11425.
The aim of our prospective study was to detect circulating epithelial cells (CEC) indicating the presence of disseminated tumor cells (DTC) in tissues affected by lymphatic and hematogenic colorectal cancer metastasis. DTC were tracked in lymph node, liver or bone marrow samples of 245 colorectal cancer patients using 2 independent RT-PCR assays for cytokeratin 20 (CK20) and guanylylcyclase C (GCC) that demonstrated a sensitivity of 1 colorectal cancer cell in 10(6) nucleated hematopoietic cells. CK20 mRNA was detected in 79% of lymph nodes, 35% of both liver lobes and 11% of bone marrow samples. GCC mRNA was found in 68% of lymph nodes, 60% of both liver lobes and 6% of bone marrow specimens. Both markers were recorded in 63% of lymph nodes, 45% of at least 1 liver lobe and 1% of bone marrow samples. There was no significant difference when comparing lymph node samples tested positive for both markers in patients with (N1/2; 65%) and without (N0; 56%) nodal involvement. The same was true when comparing the percentages of patients with and without clinically overt distant metastasis who were positive for both markers in at least 1 liver lobe (62% vs. 41%) or in bone marrow (4% vs. 0%). A score denoting the cumulative sum of tests indicating presence of CK20 and GCC mRNA in the liver was significantly related with UICC classification (p = 0.039). However, addition of lymph node results to this score decreased the correlation. The high incidence of clinically inconspicuous lymph node and liver samples tested positive for both markers emphasizes the function of these organs as primary filters for epithelial cells possibly shed from colorectal carcinomas. The potential prognostic significance of these findings warrants verification, especially regarding the importance of CEC or DTC resident in the liver of colorectal cancer patients.
我们前瞻性研究的目的是检测循环上皮细胞（CEC），以表明受淋巴和血行性结直肠癌转移影响的组织中存在播散肿瘤细胞（DTC）。使用针对细胞角蛋白20（CK20）和鸟苷酸环化酶C（GCC）的2种独立逆转录聚合酶链反应（RT-PCR）检测方法，在245例结直肠癌患者的淋巴结、肝脏或骨髓样本中追踪DTC，该检测方法在10^6个有核造血细胞中能检测到1个结直肠癌细胞。CK20 mRNA在79%的淋巴结、35%的双侧肝叶和11%的骨髓样本中被检测到。GCC mRNA在68%的淋巴结、60%的双侧肝叶和6%的骨髓标本中被发现。两种标志物均在63%的淋巴结、45%的至少1个肝叶和1%的骨髓样本中被记录。在比较有（N1/2；65%）和无（N0；56%）淋巴结受累的患者中两种标志物检测均为阳性的淋巴结样本时，无显著差异。在比较至少1个肝叶中两种标志物检测均为阳性的有和无临床明显远处转移的患者百分比（62%对41%）或骨髓中（4%对0%）时，情况也是如此。表示肝脏中存在CK20和GCC mRNA的检测累积总和的评分与国际抗癌联盟（UICC）分类显著相关（p = 0.039）。然而，将淋巴结结果加入该评分会降低相关性。两种标志物检测均为阳性的临床不明显淋巴结和肝脏样本的高发生率强调了这些器官作为可能从结直肠癌脱落的上皮细胞的主要滤过器的功能。这些发现的潜在预后意义值得验证，特别是关于结直肠癌患者肝脏中CEC或DTC的重要性。
