Uen Yih-Huei, Lu Chien-Yu, Tsai Hsiang-Lin, Yu Fang-Jung, Huang Ming-Yii, Cheng Tian-Lu, Lin Shiu-Ru, Wang Jaw-Yuan
Department of Surgery, Division of General Surgery, Chi Mei Foundation Medical Center, Taipei Medical University, Taipei, Taiwan.
Ann Surg Oncol. 2008 Aug;15(8):2120-8. doi: 10.1245/s10434-008-9961-7. Epub 2008 May 15.
To detect pre- and postoperative circulating tumor cells (CTCs) in stage I-III colorectal cancer (CRC) patients undergoing curative resection and so identify a subgroup of patients who are at high risk for relapse.
Four mRNA molecular markers including human telomerase reverse transcriptase, cytokeratin-19, cytokeratin-20, and carcinoembryonic antigen mRNA were used to detect CTCs in 438 CRC patients underwent curative resection.
Out of 438 patients, 80 CRC patients were classified to preoperative (-)/postoperative (-), 221 patients were preoperative (+)/postoperative (-), while 137 patients were preoperative (+)/postoperative (+). Univariately, postoperative relapse was significantly correlated with depth of invasion (P = 0.032), lymph node metastasis (P < 0.001), vascular invasion (P = 0.001), perineural invasion (P = 0.013), and persistent presence of CTCs (P < 0.001). Using a multivariate proportional hazards regression analysis, the presence of lymph node metastasis (P = 0.012; HR, 7.652; 95% CI: 4.162-14.827), vascular invasion (P = 0.033; HR, 4.360; 95% CI: 2.793-10.847), and the persistent presence of CTCs (P < 0.001; HR, 29.486; 95% CI: 10.281-87.792) were demonstrated to be independent predictors for postoperative relapse. Combination of these three independent predictors showed that patients with any one positive predictor had a hazard ratio of sevenfold to develop postoperative relapse (P < 0.001; HR, 7.064; 95% CI: 4.354-11.464). Furthermore, the persistent presence of CTCs was strongly correlated with poorer relapse-free survival rates (all P < 0.001).
The promising results of this study suggest that persistent presence of postoperative CTCs may be a crucial prognostic factor adjuvant to conventional tumor markers in CRC patients who have undergone curative resection. Identification of these high-risk patients of persistent CTCs positivity is important and thus could help to define patients for adjuvant therapy with this tumor entity.
检测接受根治性切除的I - III期结直肠癌(CRC)患者术前和术后的循环肿瘤细胞(CTC),从而识别出复发高危患者亚组。
使用包括人端粒酶逆转录酶、细胞角蛋白-19、细胞角蛋白-20和癌胚抗原mRNA在内的四种mRNA分子标志物,检测438例接受根治性切除的CRC患者的CTC。
438例患者中,80例CRC患者被分类为术前(-)/术后(-),221例患者为术前(+)/术后(-),而137例患者为术前(+)/术后(+)。单因素分析显示,术后复发与浸润深度(P = 0.032)、淋巴结转移(P < 0.001)、血管侵犯(P = 0.001)、神经侵犯(P = 0.013)以及CTC的持续存在(P < 0.001)显著相关。使用多因素比例风险回归分析,淋巴结转移的存在(P = 0.012;HR,7.652;95% CI:4.162 - 14.827)、血管侵犯(P = 0.033;HR,