Significance of PTEN alterations in endometrial carcinoma: A population-based study of mutations, promoter methylation and PTEN protein expression

  • Authors:
    • Helga B. Salvesen
    • Ingunn Stefansson
    • Ellen I. Kretzschmar
    • Paula Gruber
    • Nicola D. MacDonald
    • Andy Ryan
    • Ian J. Jacobs
    • Lars A. Akslen
    • Soma Das
  • View Affiliations

  • Published online on: December 1, 2004     https://doi.org/10.3892/ijo.25.6.1615
  • Pages: 1615-1623
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Abstract

Mutations in the PTEN gene are frequent in endometrial carcinoma. PTEN methylation is an alternative mechanism of gene inactivation. To elucidate different mechanisms of PTEN gene inactivation, we have studied a population-based series of endometrial carcinomas for PTEN mutations in relation to clinicopathologic characteristics, promoter methylation and protein expression. PTEN mutations were found in 54%, mainly in exons 5 and 8; with at least two different mutations in 21%. Presence of PTEN mutation was significantly correlated with young age, low FIGO-stage, endometrioid subtype, low grade, microsatellite instability and favourable prognosis. Previous studies of these tumours have observed PTEN methylation in 18% and low protein expression in 20%. Low expression of PTEN-antibody 6H2.1 was correlated with the presence of mutations in exon 8 among patients with ‘two hits’; i.e. ≥2 mutations, or mutation(s) plus methylation (p=0.001). Number of PTEN hits was significantly associated with microsatellite instability, low hMLH1 expression and hMLH1 methylation. Thus, PTEN mutations are frequent in sporadic endometrial carcinoma and define a prognostically favourable subgroup, whereas the relationship with PTEN protein expression is complex. A pathway in endometrial carcinogenesis involving PTEN mutation and microsatellite instability is confirmed, and this study also indicates the importance of PTEN and hMLH1 methylation in this pathway.

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December 2004
Volume 25 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Salvesen HB, Stefansson I, Kretzschmar EI, Gruber P, MacDonald ND, Ryan A, Jacobs IJ, Akslen LA and Das S: Significance of PTEN alterations in endometrial carcinoma: A population-based study of mutations, promoter methylation and PTEN protein expression. Int J Oncol 25: 1615-1623, 2004.
APA
Salvesen, H.B., Stefansson, I., Kretzschmar, E.I., Gruber, P., MacDonald, N.D., Ryan, A. ... Das, S. (2004). Significance of PTEN alterations in endometrial carcinoma: A population-based study of mutations, promoter methylation and PTEN protein expression. International Journal of Oncology, 25, 1615-1623. https://doi.org/10.3892/ijo.25.6.1615
MLA
Salvesen, H. B., Stefansson, I., Kretzschmar, E. I., Gruber, P., MacDonald, N. D., Ryan, A., Jacobs, I. J., Akslen, L. A., Das, S."Significance of PTEN alterations in endometrial carcinoma: A population-based study of mutations, promoter methylation and PTEN protein expression". International Journal of Oncology 25.6 (2004): 1615-1623.
Chicago
Salvesen, H. B., Stefansson, I., Kretzschmar, E. I., Gruber, P., MacDonald, N. D., Ryan, A., Jacobs, I. J., Akslen, L. A., Das, S."Significance of PTEN alterations in endometrial carcinoma: A population-based study of mutations, promoter methylation and PTEN protein expression". International Journal of Oncology 25, no. 6 (2004): 1615-1623. https://doi.org/10.3892/ijo.25.6.1615