Detection of tumor DNA at the margins of colorectal cancer liver metastasis.
Detection of tumor DNA at the margins of colorectal cancer liver metastasis.
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DOI：
10.1158/1078-0432.ccr-10-3087
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发表时间：
2011-06-01
期刊：
影响因子：
--
通讯作者：
Diaz LA Jr
中科院分区：
文献类型：
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作者：
Holdhoff M;Schmidt K;Diehl F;Aggrawal N;Angenendt P;Romans K;Edelstein DL;Torbenson M;Kinzler KW;Vogelstein B;Choti MA;Diaz LA Jr
确定结直肠癌肝转移的足够切除边缘对于优化手术技术至关重要。我们尝试通过组织病理学和遗传学分析相结合来评估切除边缘。我们评估了 12 名转移性结肠癌患者的 88 个肿瘤边缘样本，这些患者均接受了 1 至 6 个肝转移瘤的部分肝切除术。在距肿瘤边界 4、8、12 和 16 毫米处获得周围肝组织的穿刺活检。通过一种名为 BEAMing 的灵敏 PCR 技术对这些活检样本中的 DNA 进行分析，以检测相应肿瘤中鉴定出的 KRAS、PIK3CA、APC 或 TP53 突变。在每位患者切除的肿瘤中发现了突变，并用于分析肿瘤正常边界周围的 88 个样本。在这 88 个样本中，有 5 个样本的周围肝组织中可检测到肿瘤特异性突变 DNA，所有样本都在距离肿瘤边界 4 毫米以内。距肉眼可见边缘 8、12 和 16 毫米的活组织检查缺乏可检测到的突变肿瘤 DNA 以及显微镜下可见的癌细胞。对化疗具有显着放射学反应的肿瘤与主肿瘤超过 4 毫米的突变肿瘤 DNA 的任何增加无关。突变的肿瘤特异性 DNA 可以在可见肿瘤边缘之外检测到，但绝不会超过 4 毫米，即使在化疗前肿瘤较大的患者中也是如此。这些数据为确定接受肝转移切除的患者所需的手术切除范围提供了合理的基础。
Defining an adequate resection margin of colorectal cancer liver metastases is essential for optimizing surgical technique. We have attempted to evaluate the resection margin through a combination of histopathologic and genetic analyses. We evaluated 88 samples of tumor margins from 12 patients with metastatic colon cancer who each underwent partial hepatectomy of one to six liver metastases. Punch biopsies of surrounding liver tissue were obtained at 4, 8, 12 and 16 mm from the tumor border. DNA from these biopsies was analyzed by a sensitive PCR-based technique, called BEAMing, for mutations of KRAS, PIK3CA, APC, or TP53 identified in the corresponding tumor. Mutations were identified in each patient’s resected tumor and used to analyze the 88 samples circumscribing the tumor-normal border. Tumor-specific mutant DNA was detectable in surrounding liver tissue in five of these 88 samples, all within 4 mm of the tumor border. Biopsies that were 8, 12, and 16 mm from the macroscopic visible margin were devoid of detectable mutant tumor DNA as well as of microscopically visible cancer cells. Tumors with a significant radiologic response to chemotherapy were not associated with any increase in mutant tumor DNA in beyond 4 mm of the main tumor. Mutant tumor-specific DNA can be detected beyond the visible tumor margin, but never beyond 4 mm, even in patients whose tumors were larger prior to chemotherapy. These data provide a rational basis for determining the extent of surgical excision required in patients undergoing resection of liver metastases.