Open Access, Peer-reviewed
pISSN 2233-7385
eISSN 2233-7393
    Chonnam Med J. 2009 Apr;45(1):47-54. Korean.
    Published online Apr 27, 2009.
    https://doi.org/10.4068/cmj.2009.45.1.47
    Copyright © 2009 Chonnam National University Medical School
    Original Article

    The Role of PTEN Mutation in the Development of Endometrial Carcinoma

    Yoo-Duk Choi, Sung-Sun Kim, Chang-Soo Park and Jong-Hee Nam
      • Department of Pathology, Chonnam National University Medical School, Gwangju, Korea.
    Accepted March 25, 2009.

    Abstract

    Over the past 2 decades, the tendency has been to classify endometrial carcinoma into 2 different types. Type I tumors (about 80%) are endometrioid carcinomas, are often preceded by complex and atypical hyperplasia, and are associated with estrogen stimulation. Type II tumors (about 10%) are nonendometrioid carcinomas that arise occasionally from precancerous lesions that develop in atrophic endometria. It has been found that the molecular alterations of endometrioid carcinomas, including defects in DNA-mismatch repair and mutations in PTEN (phosphatase and tension homologue deleted in chromosome ten), K-ras, and beta-catenin, are different from those of the nonendometrioid carcinomas. In this study, we analyzed the PTEN mutation by direct DNA sequencing of the endometrial hyperplasia and endometrioid carcinoma in order to investigate the molecular carcinogenesis of Type I endometrial carcinoma. PTEN mutations were detected in 14 (37.8%) of 37 carcinomas, including 8 cases (21.6%) in exon 5, 1 case (2.7%) in exon 6, 5 cases (13.5%) in exon 7, and 3 cases (8.1%) in exon 8. The most frequent site of PTEN mutation was codon 130 on exon 5, which encodes the tyrosine phosphatase catalytic domain. The PTEN mutation was not associated with histologic grade, depth of invasion, or clinical stage. PTEN mutations were also shown in 3 cases (15.8%) of 19 typical endometrial hyperplasias and in 6 cases (28.6%) of 21 atypical endometrial hyperplasias. These results suggest that PTEN is an important target gene in the development of type I endometrial carcinomas and that the presence of PTEN mutations in typical and atypical endometrial hyperplasia suggest that PTEN mutations would occur as early events in the process of type I endometrial carcinogenesis.

    Keywords
    Endometrium; Hyperplasia; Carcinoma; PTEN gene; Mutation

    Figures

    Fig. 1
    On electrophoresis, each PCR product of PTEN gene was located in 375 bp for exon 5 (lane 1), 275 bp for exon 6 (lane 2), 241 bp for exon 7 (lane 3) and 399 bp for exon 8 (lane 4) of PTEN gene (M; 100 bp ladder marker).

    Fig. 2
    Examples of conversion, hetero-form, and insertion. A G-to-A conversion in exon 5 of PTEN gene resulted in a nonsense mutation in endometrial carcinoma. An A-to-G transition in exon 5 caused a missense mutation. An insertion of A in exon 7 generally occurred in non-coding region.

    Tables

    Table 1
    Primers of PTEN

    Table 2
    Mutation of PTEN in endometrial carcinoma

    Table 3
    Mutation of PTEN of endometrial carcinoma according to pathologic parameters

    Table 4
    Mutation of PTEN in endometrial hyperplasia

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    MeSH Terms
    Carcinoma, Endometrioid
    Catalytic Domain
    Codon
    Endometrial Hyperplasia
    Endometrial Neoplasms
    Endometrium
    Estrogens
    Exons
    Female
    Hyperplasia
    Sequence Analysis, DNA
    Tyrosine
    beta Catenin
    Metrics
    Share
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    Tables
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