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Departments of Pathology [R. L. L., C. B. C., M. S. B., B. v. R., R. J. K., L. H. E.], Gynecology and Obstetrics [R. J. K., L. H. E.], and Oncology [L. H. E], The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196
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.
1 Supported by NIH Grant CA66720 (to L. H. E.). R. L. L. is a Research Training Fellow of the Howard Hughes Medical Institute.
2 To whom requests for reprints should be addressed. Present address: Department of Pathology, Cornell University Medical College, 1300 York Avenue, New York, NY 10021. Phone: (212) 746-6447; Fax: (212) 746-4483; E-mail: lhellens@mail.med.cornell.edu.
Received 4/ 7/98. Accepted 6/ 8/98.
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