A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer.
A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer.
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发表时间：
1998-11
期刊：
影响因子：
11.2
通讯作者：
C. Boland;S. Thibodeau;S. Hamilton;D. Sidransky;J. Eshleman;R. Burt;S. Meltzer;M. Rodriguez-Bigas;R. Fodde;G. Ranzani;S. Srivastava
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作者：
C. Boland;S. Thibodeau;S. Hamilton;D. Sidransky;J. Eshleman;R. Burt;S. Meltzer;M. Rodriguez-Bigas;R. Fodde;G. Ranzani;S. Srivastava
1997年12月，国家癌症研究所主办了"癌症检测和家族易感性中微卫星不稳定性和RER表型国际研讨会"，以审查和统一该领域。讲习班核可了下列建议。(a)与肿瘤中DNA错配修复缺陷相关的基因组不稳定性形式被称为微卫星不稳定性（MSI）。(b)一个由五颗微型卫星组成的小组已经过验证，并被建议作为今后该领域研究的参考小组。肿瘤可以基于以下特征来表征：高频MSI（MSI-H），如果五种标志物中的两种或更多种显示不稳定性（即，有插入/缺失突变），和低频率MSI（MSI-L），如果只有一个五个标志物显示不稳定。微卫星稳定（MSS）和低频率MSI（MSI-L）之间的区别，只能完成，如果使用更多的标记。(c)MSI-H肿瘤鉴定出独特的临床和病理表型，其占结肠直肠癌的约15%，而MSI-L和MSS肿瘤似乎在表型上相似。MSI-H结直肠肿瘤主要在近端结肠中发现，具有独特的组织病理学特征，并且与阶段匹配的MSI-L或MSS肿瘤相比，与侵袭性较低的临床过程相关。临床前模型表明，这些肿瘤可能对某些化疗药物诱导的细胞毒性具有抗性。对MSI-L的影响尚不清楚。(d)MSI可以在新鲜或固定的肿瘤标本中同样良好地测量;病理标本的显微解剖被推荐用于富集肿瘤组织;并且需要正常组织来记录MSI的存在。(e)1996年制定的“贝塞斯达指南”旨在帮助选择肿瘤进行微卫星分析，该指南得到了认可。(f)回顾了非结肠肿瘤中微卫星改变的谱，并得出结论，上述建议仅适用于结直肠肿瘤。(g)提出了一项研究议程。
In December 1997, the National Cancer Institute sponsored "The International Workshop on Microsatellite Instability and RER Phenotypes in Cancer Detection and Familial Predisposition," to review and unify the field. The following recommendations were endorsed at the workshop. (a) The form of genomic instability associated with defective DNA mismatch repair in tumors is to be called microsatellite instability (MSI). (b) A panel of five microsatellites has been validated and is recommended as a reference panel for future research in the field. Tumors may be characterized on the basis of: high-frequency MSI (MSI-H), if two or more of the five markers show instability (i.e., have insertion/deletion mutations), and low-frequency MSI (MSI-L), if only one of the five markers shows instability. The distinction between microsatellite stable (MSS) and low frequency MSI (MSI-L) can only be accomplished if a greater number of markers is utilized. (c) A unique clinical and pathological phenotype is identified for the MSI-H tumors, which comprise approximately 15% of colorectal cancers, whereas MSI-L and MSS tumors appear to be phenotypically similar. MSI-H colorectal tumors are found predominantly in the proximal colon, have unique histopathological features, and are associated with a less aggressive clinical course than are stage-matched MSI-L or MSS tumors. Preclinical models suggest the possibility that these tumors may be resistant to the cytotoxicity induced by certain chemotherapeutic agents. The implications for MSI-L are not yet clear. (d) MSI can be measured in fresh or fixed tumor specimens equally well; microdissection of pathological specimens is recommended to enrich for neoplastic tissue; and normal tissue is required to document the presence of MSI. (e) The "Bethesda guidelines," which were developed in 1996 to assist in the selection of tumors for microsatellite analysis, are endorsed. (f) The spectrum of microsatellite alterations in noncolonic tumors was reviewed, and it was concluded that the above recommendations apply only to colorectal neoplasms. (g) A research agenda was recommended.