GRJ 704, Gastrointestinal Unit, Massachusetts General Hospital, 50 Blossom Street, Boston, MA, 02114, USA,
Dig Dis Sci. 2014 Sep;59(9):2255-63. doi: 10.1007/s10620-014-3134-2. Epub 2014 Apr 5.
The factors underlying the development of interval colon cancers are not well defined and are likely heterogeneous. We sought to determine whether there are distinct molecular properties associated with interval colon cancers.
Colon cancers diagnosed within 5 years of a complete and well-prepped colonoscopic examination were identified over a 7-year period at a single institution. The clinical and pathological features of the tumors were defined. Analysis of DNA mismatch repair (MMR) and genotyping of a panel of oncogenes associated with colon cancer were performed.
Forty-two interval colon cancers were diagnosed at an average age of 70 years. 69 % of tumors were located in the right colon. 41 % of tumors exhibited DNA microsatellite instability (MSI). Loss of staining of DNA MMR proteins by immunohistochemistry (IHC) was confirmed in 82 % of the MSI-positive tumors. Among tumors with abnormal MSI and IHC, 54 % exhibited somatic methylation of the MLH1 promoter, but the remaining 43 % exhibited molecular features indicative of underlying Lynch syndrome (LS). The frequency of somatic mutations in the KRAS, BRAF, NRAS, and PIK3CA oncogenes was similar between interval cancer cases and controls.
Interval colon cancers are not distinguished by the activation of the KRAS, NRAS, BRAF, or PIK3CA oncogenic pathways. However, MSI pathway defects are present in a significant proportion of interval colon cancers. Underlying LS may explain nearly half of these MSI-positive cases, and the remaining cases appear to represent sporadic serrated pathway tumors.
导致间期结肠癌发生的因素尚不清楚，而且可能具有异质性。我们试图确定是否存在与间期结肠癌相关的独特分子特征。
在单个机构的 7 年期间，鉴定了在完全且准备充分的结肠镜检查后 5 年内诊断出的结肠癌。定义了肿瘤的临床和病理特征。对 DNA 错配修复（MMR）进行分析，并对与结肠癌相关的一组癌基因进行基因分型。
42 例间期结肠癌在平均年龄为 70 岁时被诊断出来。69%的肿瘤位于右结肠。41%的肿瘤表现出 DNA 微卫星不稳定性（MSI）。免疫组化（IHC）证实 82%的 MSI 阳性肿瘤中存在 DNA MMR 蛋白染色丢失。在异常 MSI 和 IHC 的肿瘤中，54%表现出 MLH1 启动子的体细胞甲基化，但其余 43%表现出潜在林奇综合征（LS）的分子特征。KRAS、BRAF、NRAS 和 PIK3CA 癌基因的体细胞突变频率在间期癌病例和对照之间相似。
间期结肠癌不能通过 KRAS、NRAS、BRAF 或 PIK3CA 致癌途径的激活来区分。然而，MSI 途径缺陷存在于相当一部分间期结肠癌中。潜在的 LS 可能解释了近一半的这些 MSI 阳性病例，而其余病例似乎代表散发性锯齿状途径肿瘤。
