Clinicopathologic and Molecular Characteristics of Synchronous Colorectal Cancers: Heterogeneity of Clinical Outcome Depending on Microsatellite Instability Status of Individual Tumors
Clinicopathologic and Molecular Characteristics of Synchronous Colorectal Cancers: Heterogeneity of Clinical Outcome Depending on Microsatellite Instability Status of Individual Tumors
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DOI：
10.1097/dcr.0b013e31823c46ce
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发表时间：
2012-02-01
影响因子：
3.9
通讯作者：
Kang, Gyeong H.
中科院分区：
文献类型：
--
作者：
Bae, Jeong M.;Cho, Nam-Yun;Kang, Gyeong H.
背景技术：染色体不稳定性、微卫星不稳定性和表观遗传学不稳定性对同步性结直肠癌发生的影响存在争议。目的：本研究旨在探讨微卫星不稳定性和表观遗传学不稳定性在同步性结直肠癌发生中的相对作用。设计：这是一项回顾性研究的医疗记录与组织学，免疫组织化学和分子检测的储存组织样本。研究在韩国首尔国立大学医院进行。患者：共纳入46例同时性结直肠癌患者和105例孤立性结直肠癌患者。临床病理和分子特征，包括微卫星不稳定性，错配修复基因表达，CpG岛甲基化表型，结果：同步性肿瘤患者男性多于孤立性肿瘤患者，且有单个肿瘤在左、右结肠共定位的趋势。MSI缺陷型癌症在同步性癌症中比在孤立性癌症中更常见。CpG岛甲基化表型高、KRAS和BRAF突变的频率在同时性癌和孤立性癌之间没有差异。在总生存期或无进展生存期方面，同步癌和孤立癌之间没有观察到差异。在同步癌症组中，个体肿瘤微卫星不稳定状态不一致的患者临床结局最差，而个体肿瘤微卫星不稳定缺陷状态一致的患者临床结局最好。分子分析只进行癌性lesions.CONCLUSIONS：我们的研究结果表明，微卫星的不稳定性起着更重要的作用比表观遗传不稳定性在发展中的同步性结直肠癌，和信息之间的一致或不一致的微卫星不稳定性状态个体肿瘤可能有助于预测临床结果的同步性结直肠癌。
BACKGROUND: The contribution of chromosomal instability, microsatellite instability, and epigenetic instability to the development of synchronous colorectal carcinomas is controversial.OBJECTIVE: This study aimed to investigate the relative roles of microsatellite instability and epigenetic instability in the development of synchronous colorectal cancers.DESIGN: This was a retrospective study of medical records with histologic, immunohistochemical, and molecular examination of stored tissue samples.SETTING: The study took place at Seoul National University Hospital, Korea.PATIENTS: A total of 46 patients with synchronous colorectal cancers and 105 patients with solitary colorectal cancers were included.MAIN OUTCOME MEASURES: Clinicopathologic and molecular characteristics including microsatellite instability, mismatch repair gene expression, CpG island methylator phenotype, and mutation of KRAS and BRAF were analyzed.RESULTS: Patients with synchronous tumors were more likely to be men than those with solitary tumors and had a tendency toward colocalization of individual tumors in the left or right colon. MSI-deficient cancers were more frequent in synchronous than in solitary cancers. The frequencies of CpG island methylator phenotype-high and KRAS and BRAF mutations were not different between synchronous and solitary cancers. No differences between synchronous cancers and solitary cancers were observed in overall survival or progression-free survival. Within the synchronous cancer group, patients with individual tumors discordant for microsatellite instability status had the worst clinical outcome, whereas those with individual tumors concordant for microsatellite instability-deficient status had the best clinical outcome.LIMITATIONS: The study was limited by its retrospective nature. Molecular analysis was performed only on cancerous lesions.CONCLUSIONS: Our findings suggest that microsatellite instability plays a more important role than does epigenetic instability in the development of synchronous colorectal cancers, and that information regarding concordant or discordant microsatellite instability status between individual tumors might help to predict clinical outcome of synchronous colorectal cancers.