Archives of Gynecology and Obstetrics

, Volume 299, Issue 6, pp 1511–1524 | Cite as

PTEN expression in endometrial hyperplasia and risk of cancer: a systematic review and meta-analysis

  • Antonio Raffone
  • Antonio TravaglinoEmail author
  • Gabriele Saccone
  • Martina Viggiani
  • Pierluigi Giampaolino
  • Luigi Insabato
  • Antonio Mollo
  • Giuseppe De Placido
  • Fulvio Zullo



Rates of progression of endometrial hyperplasia (EH) to endometrial cancer (EC) are highly variable. Among several prognostic markers, PTEN has been recommended by ESMO–ESGO–ESTRO to identify premalignant EH. However, its prognostic accuracy is unclear. Thus, we aimed to assess: (1) the association between PTEN loss in EH and risk of cancer, and (2) the prognostic accuracy of PTEN immunohistochemistry in EH.


Electronic databases were searched from their inception to June 2018. All studies assessing PTEN immunohistochemistry in EH and the presence of EC on subsequent hysterectomy were included. Odds ratio (OR), sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (LR + and LR−) and area under the curve (AUC) on SROC curves were calculated with subgroup analysis (short/long-term; atypical/non-atypical EH).


Nine retrospective studies assessing 933 EH were included. PTEN loss in EH was significantly associated with increased risk of EC (OR = 3.32, p = 0.001). The association was significant only on the short term ( < 1 year) (OR = 3.45, p = 0.002) and in atypical EH (OR = 1.89, p = 0.01). For overall analysis and short-term/atypical EH subgroup the prognostic accuracy was low, with sensitivity = 0.58 and 0.68, specificity = 0.60 and 0.48, VPp = 0.41 and 0.54, VPN = 0.75 and 0.63, LR +  = 1.80 and 1.37, LR − =  0.62 and 0.56, AUC = 0.687 and 0.721, respectively.


PTEN loss in EH is a risk factor for EC, but is not reliable in predicting the risk of EC. In atypical EH, PTEN loss is associated with a risk of concurrent EC of over 50%. This information might integrate the patients’ informed consent for the choice of treatment (conservative/hysterectomy), especially in borderline cases. In conservative approach, PTEN loss might suggest closer follow-up.


EIN Endometrial intraepithelial neoplasia Endometrioid adenocarcinoma Immunohistochemical Prognosis Tumor suppressor protein phosphatase Tensin homolog 


Author contributions

AR, AT: protocol/project development, data collection, data analysis, and manuscript writing/editing. GS: data analysis and manuscript writing/editing. MV: protocol/project development and data collection. PG: protocol/project development and manuscript writing/editing. LI: manuscript writing/editing and study supervision. AM: protocol/project development and study supervision. GDP: protocol/project development and study supervision. FZ: protocol/project development, manuscript writing/editing, and study supervision.


No financial support was received for this study.

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Antonio Raffone
    • 1
  • Antonio Travaglino
    • 2
    Email author
  • Gabriele Saccone
    • 1
  • Martina Viggiani
    • 3
  • Pierluigi Giampaolino
    • 4
  • Luigi Insabato
    • 2
  • Antonio Mollo
    • 1
  • Giuseppe De Placido
    • 1
  • Fulvio Zullo
    • 1
  1. 1.Gynecology and Obstetrics Unit, Department of Neuroscience, Reproductive Sciences and Dentistry, School of MedicineUniversity of Naples Federico IINaplesItaly
  2. 2.Anatomic Pathology Unit, Department of Advanced Biomedical Sciences, School of MedicineUniversity of Naples Federico IINaplesItaly
  3. 3.Oncology Unit, Department of Clinical Medicine and Surgery, School of MedicineUniversity of Naples Federico IINaplesItaly
  4. 4.Obstetrics and Gynecology Unit, Department of Public Health, School of MedicineUniversity of Naples Federico IINaplesItaly

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