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Molecular and Pathologic Aspects of Endometrial Carcinogenesis

Jonathan L. Hecht, George L. Mutter

From the Department of Pathology, Beth Israel Hospital; Department of Pathology, Brigham and Women's Hospital, Boston, MA

Address reprint requests to Department of Pathology, Beth-Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215; e-mail: jlhecht{at}BIDMC.harvard.edu

Endometrial cancer is the most common gynecological malignancy, with 41,000 new cases projected in the United States for 2006. Two different clinicopathologic subtypes are recognized: the estrogen-related (type I, endometrioid) and the non–estrogen-related types (type II, nonendometrioid such as papillary serous and clear cell). The morphologic differences in these cancers are mirrored in their molecular genetic profile with type I showing defects in DNA-mismatch repair and mutations in PTEN, K-ras, and beta-catenin, and type II showing aneuploidy and p53 mutations. This article reviews the genetic aspects of endometrial carcinogenesis and progression. We will define the precursor lesion of type I endometrioid cancer and the role of genetics and estrogen in its progression.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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