Levine R L, Cargile C B, Blazes M S, van Rees B, Kurman R J, Ellenson L H
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
Cancer Res. 1998 Aug 1;58(15):3254-8.
The two most common types of genetic alterations yet identified in uterine endometrioid carcinoma (UEC) are PTEN mutations and microsatellite instability (MI). Furthermore, MI-positive UECs (defined as tumors with detectable alterations at two or more different microsatellite loci) are significantly more likely to contain PTEN mutations than are MI-negative UECs. To determine whether PTEN inactivation is a relatively early event in endometrial tumorigenesis, we evaluated complex atypical hyperplasia (CAH), the direct precursor to UEC, for the presence of PTEN mutations. Mutations were present in 3 of 11 (27%) CAHs with synchronous UEC and in 4 of 18 (22%) CAHs that were not associated with invasive carcinoma. One case with synchronous CAH and UEC contained a germ-line PTEN mutation. In addition, we evaluated the same series of CAHs for MI. We identified four MI-positive CAHs with synchronous UEC but did not detect the MI phenotype in any CAHs without associated invasive carcinoma. A PTEN-mutant (germ-line mutation) MI-negative CAH was synchronous with a PTEN-mutant MI-positive UEC. These results suggest that mutation of PTEN can be an early event in the pathogenesis of UEC and may precede the development of the MI phenotype in a subset of cases.
子宫子宫内膜样癌（UEC）中迄今已确定的两种最常见的基因改变类型是PTEN突变和微卫星不稳定性（MI）。此外，MI阳性的UEC（定义为在两个或更多不同微卫星位点有可检测改变的肿瘤）比MI阴性的UEC更有可能含有PTEN突变。为了确定PTEN失活是否是子宫内膜肿瘤发生过程中相对较早的事件，我们评估了UEC的直接前体——复杂性非典型增生（CAH）中PTEN突变的情况。在11例伴有同步UEC的CAH中有3例（27%）存在突变，在18例与浸润性癌无关的CAH中有4例（22%）存在突变。1例伴有同步CAH和UEC的病例含有种系PTEN突变。此外，我们评估了同一组CAH的MI情况。我们在4例伴有同步UEC的CAH中发现了MI阳性，但在任何无相关浸润性癌的CAH中均未检测到MI表型。1例PTEN突变（种系突变）的MI阴性CAH与1例PTEN突变的MI阳性UEC同步发生。这些结果表明，PTEN突变可能是UEC发病机制中的早期事件，并且在一部分病例中可能先于MI表型的出现。
