Boland C R, Thibodeau S N, Hamilton S R, Sidransky D, Eshleman J R, Burt R W, Meltzer S J, Rodriguez-Bigas M A, Fodde R, Ranzani G N, Srivastava S
University of California, San Diego, La Jolla 92093-0688, USA.
Cancer Res. 1998 Nov 15;58(22):5248-57.
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.
1997年12月，美国国立癌症研究所主办了“癌症检测与家族易感性中的微卫星不稳定性和错配修复缺陷表型国际研讨会”，以对该领域进行回顾和统一。研讨会认可了以下建议。(a) 肿瘤中与DNA错配修复缺陷相关的基因组不稳定性形式应称为微卫星不稳定性（MSI）。(b) 一组五个微卫星已得到验证，推荐作为该领域未来研究的参考组。肿瘤可根据以下情况进行特征描述：高频MSI（MSI-H），如果五个标记中有两个或更多显示不稳定性（即有插入/缺失突变）；低频MSI（MSI-L），如果五个标记中只有一个显示不稳定性。只有使用更多标记才能区分微卫星稳定（MSS）和低频MSI（MSI-L）。(c) 为MSI-H肿瘤确定了一种独特的临床和病理表型，MSI-H肿瘤约占结直肠癌的15%，而MSI-L和MSS肿瘤在表型上似乎相似。MSI-H结直肠肿瘤主要见于近端结肠，具有独特的组织病理学特征，与分期匹配的MSI-L或MSS肿瘤相比，临床病程侵袭性较小。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。MSI-L的影响尚不清楚。(d) MSI可在新鲜或固定的肿瘤标本中同样良好地测量；建议对病理标本进行显微切割以富集肿瘤组织；需要正常组织来证明MSI的存在。(e) 认可1996年制定的“贝塞斯达指南”，以协助选择用于微卫星分析的肿瘤。(f) 对非结肠肿瘤中微卫星改变的范围进行了回顾，得出的结论是上述建议仅适用于结直肠肿瘤。(g) 推荐了一项研究议程。
