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Predicting the Coexistence of an Endometrial Adenocarcinoma in the Presence of Atypical Complex Hyperplasia: Immunohistochemical Analysis of Endometrial Samples
  1. Elisabeth J.M. Robbe, MD*,
  2. Sander M.J. van Kuijk, MSc,,
  3. Ella M. de Boed§,
  4. Luc J.M. Smits, PhD,
  5. Anneke A.M. van der Wurff, MD, PhD§,
  6. Roy F.P.M. Kruitwagen, MD, PhD and
  7. Johanna M.A. Pijnenborg, MD, PhD
  1. *Department of Obstetrics and Gynecology, UZ Brussel, Brussels, Belgium;
  2. Department of Epidemiology, Caphri School for Public Health and Primary Care, and
  3. Department of Obstetrics and Gynaecology and GROW– School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht;
  4. §Department of Pathology, St Elisabeth Hospital; and
  5. Department of Obstetrics and Gynecology, TweeSteden Hospital, Tilburg, The Netherlands.
  1. Address correspondence and reprint requests to Elisabeth J.M. Robbe, MD, Department Obstetrics and Gynaecology, UZ Brussel, Laarbeeklaan 101, 1090 Jette, Belgium. E-mail: liselotterobbe{at}


Objective This study aimed to determine whether immunohistochemical markers in complex atypical endometrial hyperplasia could predict the presence of a concurrent endometrial carcinoma.

Methods Endometrial biopsies of 39 patients with complex atypical hyperplasia were selected retrospectively between 1999 and 2006. Only patients who underwent a hysterectomy were included. A coexisting endometrial carcinoma was present in 25 patients (64%). Immunohistochemical analysis was performed on formalin-fixed paraffin-embedded sections of the endometrial biopsies, using antibodies for MIB-1, β-catenin, E-cadherin, p53, PTEN, CD44, HER2-neu, survivin, COX-2, tenascin, and bcl-2. To evaluate the potential utility of these markers, a prediction model was constructed.

Results In the univariate analysis, expressions of both PTEN and HER2-neu were significantly different between the groups with and without a coexisting endometrial carcinoma (P < 0.05). Loss of PTEN staining was found in 13 (54%) and 1 (7%) of the patients with and without a coexistent carcinoma, respectively (odds ratio, 16.55; 95% confidence interval [CI], 1.87–146.65). HER2-neu expression was found in only 2 (8.6%) and 6 (43%) patients with and without a coexistent carcinoma, respectively, and was excluded from further analysis because of its low expression. A prediction model containing PTEN expression only showed an area under the curve of 73.4% (95% CI, 57.3%–89.6%). After adding MIB-1 and p53, discriminative power improved to 87.2% (95% CI, 75.1%–99.3%).

Conclusions This study showed that PTEN expression in complex endometrial hyperplasia is a promising factor for the prediction of the presence of a coexisting endometrial carcinoma, and prediction may even better when MIB-1 and p53 expressions are considered simultaneously.

  • Atypical endometrial hyperplasia
  • Endometrial carcinoma
  • PTEN
  • Coexistent carcinoma
  • Prediction
  • Immunohistochemistry

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  • The authors declare no conflicts of interest.