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Gene Expression Profiling of Endometrial Adenocarcinomas Reveals Increased Apolipoprotein E Expression in Poorly Differentiated Tumors
  1. Jutta Huvila, MD*,
  2. Annika Brandt, PhD,
  3. Clarissa Rios Rojas, BSc,
  4. Salla Pasanen, PhLic,
  5. Lauri Talve, MD, PhD,
  6. Pirkko HirsimÄKi, PhD,
  7. Vidal Fey, PhD,
  8. Leena KytÖMÄKi, MSc,
  9. Pekka Saukko§,
  10. Olli CarpÉN,
  11. Juhani T. Soini, PhD,
  12. Seija GrÉNman, MD, PhD* and
  13. Annika Auranen, MD, PhD*
  1. *Department of Obstetrics and Gynecology, Turku University Hospital;
  2. Turku Centre for Biotechnology;
  3. Department of Pathology, Turku University Hospital;
  4. §Department of Forensic Medicine, Turku University; and
  5. Turku University of Applied Sciences, Turku, Finland.
  1. Address correspondence and reprint requests to Annika Auranen, MD, PhD, Department of Obstetrics and Gynecology, Turku University Hospital, PB 52, FIN-20521 Turku, Finland. E-mail: annika.auranen{at}tyks.fi.

Abstract

Introduction: Tumor grade is one of the most important prognostic factors in endometrioid endometrial adenocarcinoma. Amplification of oncogenes, such as Her2/neu, or loss of function of tumor suppressor genes, such as p53, are known to be associated with poor prognosis, but additional factors influencing clinical behavior are likely to exist. To examine the biological differences between low-grade and high-grade endometrioid endometrial adenocarcinomas, we compared gene expression in these 2 types of tumors.

Methods: Six well-differentiated adenocarcinomas and 7 poorly differentiated adenocarcinomas were studied with 2 different microarray platforms, Affymetrix and Illumina. The expression of the most differentially expressed gene on both platforms was further studied in 34 endometrial adenocarcinoma samples (10 well differentiated, 9 moderately differentiated, and 15 poorly differentiated) using real-time reverse transcription-polymerase chain reaction.

Results: The most differentially expressed gene on both platforms was Apolipoprotein E (APOE). In the poorly differentiated adenocarcinomas, APOE was overexpressed 13.1-fold (P = 0.001) and 9.7-fold (P = 0.007) when compared with well- and moderately differentiated tumors, respectively. There was no difference in APOE expression between well- and moderately differentiated adenocarcinomas.

Conclusions: Increased expression of APOE might represent a late event in the progression of well-differentiated endometrioid endometrial adenocarcinoma to a poorly differentiated endometrioid endometrial adenocarcinoma. Although increased APOE expression has been previously reported in other malignancies, this is the first study to suggest that APOE might also have a role in endometrioid endometrial cancer.

  • Endometrial cancer
  • Gene expression
  • Differentiation
  • Apolipoprotein E

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Footnotes

  • This study was supported by a grant from the Finnish Medical Foundation (Suomen Lääketieteen Säätiö) and by the Southwestern Finland Hospital District EVO grant. Jutta Huvila has been partly supported by a grant from the K. Albin Johansson Foundation.

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