PTEN mutations and microsatellite instability in complex atypical hyperplasia, a precursor lesion to uterine endometrioid carcinoma.
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.
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196, USA.
R L
RL
Levine
C B
CB
Cargile
M S
MS
Blazes
B
B
van Rees
R J
RJ
Kurman
L H
LH
Ellenson
D018269:Carcinoma, Endometrioid / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004714:Endometrial Hyperplasia / Q000235:genetics*; D005091:Exons; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D010641:Phenotype; D011230:Precancerous Conditions / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*; D012189:Retrospective Studies; D014594:Uterine Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm; D017027:Protein Tyrosine Phosphatases