Different types of microsatellite instability in ovarian carcinoma

✍ Scribed by Gad Singer; Thore Kallinowski; Arndt Hartmann; Wolfgang Dietmaier; Peter J. Wild; Peter Schraml; Guido Sauter; Michael J. Mihatsch; Holger Moch

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: French
• Weight: 78 KB
• Volume: 112
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.20455

✦ Synopsis

Abstract

Microsatellite instability at mono‐ and dinucleotide repeats is the hallmark of the hereditary non‐polyposis cancer syndrome (HNPCC) and is related to deficient DNA mismatch repair. In contrast, a distinct form of microsatellite instability at selective tetranucleotide repeats (EMAST or elevated microsatellite alterations at selected tetranucleotides) was described in several non‐HNPCC cancer types. EMAST is probably unrelated to mismatch repair defects. We investigated the frequency of microsatellite instability at mononucleotide, dinucleotide and tetranucleotide repeats in a series of 75 ovarian carcinomas (53 serous and 22 non‐serous). Microsatellite analysis was carried out using 5 mono‐ and dinucleotide markers from the National Cancer Institute Consensus Panel and 6 tetranucleotide markers, which have been reported as frequently unstable in the literature. High frequency of microsatellite instability (MSI‐H) at mono‐ and dinucleotide repeats was observed in 9% and a low frequency (MSI‐L) in 21% of serous carcinomas. MSI‐H was detected in 4% and MSI‐L in 18% of non‐serous carcinomas. Nine percent of serous carcinomas showed instability at multiple and 9% at single tetranucleotide loci. All non‐serous carcinomas were stable at tetranucleotide loci. In summary, EMAST (e.g., tumors with tetranucleotide instability without concomitant MSI‐H) was observed in 13% of ovarian serous carcinomas. All EMAST positive tumors were of advanced stage. We conclude that EMAST occurs as a distinct form of microsatellite instability in ovarian cancer. EMAST seems to be particularly frequent in advanced serous carcinomas. Its clinical significance needs to be investigated. © 2004 Wiley‐Liss, Inc.