Syngal Sapna, Stoffel Elena, Chung Daniel, Willett Christopher, Schoetz David, Schroy Paul, Jagadeesh Deepa, Morel Kathleen, Ross Michael
Division of Population Sciences, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Cancer. 2006 Jan 15;106(2):277-83. doi: 10.1002/cncr.21558.
Whether stool DNA abnormalities arise solely from colorectal neoplastic lesions or are due to more pervasive field effects is not known. In the current study, the authors conducted a prospective multicenter study to evaluate the performance of stool-based DNA testing in a large cohort and to examine whether the findings before treatment persist after surgical resection and/or adjuvant therapy.
Patients with newly diagnosed colorectal carcinoma or advanced adenomas (AA) provided stool samples before therapy, 1-3 months after surgical resection, and 6-9 months postresection. Stool samples were analyzed using the multi-target DNA assay panel (MTAP) consisting of 23 markers: 21 mutations in the p53, K-ras, and APC genes, a microsatellite instability marker (BAT-26), and the DNA integrity assay (DIA), a marker of loss of apoptosis.
Overall, 49 of 91 individuals (54%) tested positive with the MTAP test. The sensitivity of the MTAP test was 63% for invasive tumors compared with 26% for AA. Individuals whose lesions had a more advanced TNM stage or were located distal to the splenic flexure were significantly more likely to have a positive MTAP test. Of the 79 samples collected at 1-3 months after surgical resection of the neoplasm, 14 (18%) had a positive MTAP result, 12 of which were positive for DIA only. Of those collected at 6-9 months of follow-up, 5 of 72 (7%) tested positive on the MTAP panel.
Although many samples collected 1-3 months after surgical resection of the colorectal neoplasm tested positive on the MTAP, most were negative by 6-9 months, indicating that stool DNA abnormalities disappear after treatment of the neoplastic lesions. Surgery and chemoradiation appear to induce transient DIA abnormalities that may be independent of the presence of neoplasia.
粪便DNA异常是仅源于结直肠肿瘤性病变还是由于更广泛的场效应所致尚不清楚。在本项研究中，作者开展了一项前瞻性多中心研究，以评估基于粪便的DNA检测在一大群人中的性能，并检查治疗前的检测结果在手术切除和/或辅助治疗后是否仍然存在。
新诊断为结直肠癌或高级别腺瘤（AA）的患者在治疗前、手术切除后1 - 3个月以及切除后6 - 9个月提供粪便样本。使用由23种标志物组成的多靶点DNA检测面板（MTAP）分析粪便样本：p53、K-ras和APC基因中的21种突变、一个微卫星不稳定标志物（BAT-26）以及DNA完整性检测（DIA），后者是细胞凋亡缺失的标志物。
总体而言，91名个体中有49名（54%）MTAP检测呈阳性。MTAP检测对浸润性肿瘤的敏感性为63%，而对AA的敏感性为26%。病变处于更晚期TNM分期或位于脾曲远端的个体MTAP检测呈阳性的可能性显著更高。在肿瘤手术切除后1 - 3个月收集的79份样本中，14份（18%）MTAP结果呈阳性，其中12份仅DIA呈阳性。在随访6 - 9个月收集的样本中，72份中有5份（7%）MTAP检测呈阳性。
尽管在结直肠肿瘤手术切除后1 - 3个月收集的许多样本MTAP检测呈阳性，但到6 - 9个月时大多数样本呈阴性，这表明肿瘤性病变治疗后粪便DNA异常消失。手术和放化疗似乎会诱导短暂的DIA异常，这可能与肿瘤形成无关。
