Expression of PAX2 and PTEN in Oestrogen-Driven Endometrial Hyperplasia and Neoplasia

  • Manoj Gopal MadakshiraEmail author
  • Praveer Ranjan
Original Article



Endometrial hyperplasia is of paramount clinical implication as it is usually seen to precede endometrioid adenocarcinoma. However, clinicians and pathologists have always been uncertain about the distinction between innocuous hyperplasia from their sinister counterparts. This has serious implications, for the latter lesion has a greater propensity for progressing into adenocarcinoma and needs deft clinical intervention in the form of adequate progestational exposure or surgery.


Thirty cases diagnosed as endometrial hyperplasia on endometrial biopsies were retrieved from the archives and reclassified as per the EIN criteria. Thirty cases each of proliferative endometrium and endometrioid carcinoma were also included. Immunohistochemistry with antibodies against PAX2 and PTEN was performed, and the extent of loss of expression was scored.


A total of ten cases of EIN were identified, all of whom were initially diagnosed as complex hyperplasia with atypia. All cases of proliferative endometrium showed retained expression of PAX2 and PTEN. In contrast, all cases of endometrioid carcinoma showed complete loss of PAX2 and PTEN. The EIN cases showed partial loss of both PAX2 and PTEN expression. Loss of PAX2 expression in EIN showed a specificity and positive predictive value of 90% and 83.33%, respectively.


The advent of the EIN criteria has made identification of clinically significant endometrial precancerous lesion more acceptable and reproducible. However, in cases of ambiguity, the use of antibodies against certain protein molecules which reflect the genes involved in the stepwise carcinogenesis would be of great utility in the hands of the pathologist. In comparison with PTEN, the use of PAX2, which gives a crisp nuclear positivity and has a lower percentage of loss of expression in normal endometrium, can be used as part of the algorithm in accurately identifying the precancerous endometrium.


Endometrium Neoplasia PAX2 PTEN 



The authors acknowledge the efforts of the technical staff at the Department of Pathology, AFMC in exceution of the project. The authors also acknowledge the grant extended by the Armed Forced Medical Research Committee for conducting the research.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Kurman RJ. Blaustein's pathology of the female genital tract. Berlin: Springer; 2013.Google Scholar
  2. 2.
    Jarboe EA, Mutter GL. Endometrial intraepithelial neoplasia. In: Wick MR, editor. Seminars in diagnostic pathology. Amsterdam: Elsevier; 2010Google Scholar
  3. 3.
    Owings RA, Quick CM. Endometrial intraepithelial neoplasia. Arch Pathol Lab Med. 2014;138(4):484–91.CrossRefGoogle Scholar
  4. 4.
    Yang HP, et al. PTEN expression in benign human endometrial tissue and cancer in relation to endometrial cancer risk factors. Cancer Causes Control. 2015;26(12):1729–36.CrossRefGoogle Scholar
  5. 5.
    Maxwell GL, et al. Mutation of the PTEN tumor suppressor gene in endometrial hyperplasias. Can Res. 1998;58(12):2500–3.Google Scholar
  6. 6.
    Mutter GL, et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst. 2000;92(11):924–30.CrossRefGoogle Scholar
  7. 7.
    Monte NM, et al. Joint loss of PAX2 and PTEN expression in endometrial precancers and cancer. Can Res. 2010;70(15):6225–322.CrossRefGoogle Scholar
  8. 8.
    Mutter GL. Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? Gynecol Oncol. 2000;76(3):287–90.CrossRefGoogle Scholar
  9. 9.
    Brinton LA, et al. Serum estrogens and estrogen metabolites and endometrial cancer risk among postmenopausal women. Cancer Epidemiol Prev Biomark. 2016;25(7):1081–9.CrossRefGoogle Scholar
  10. 10.
    Wu H, et al. Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature. 2005;438(7070):981.CrossRefGoogle Scholar
  11. 11.
    Allison KH, et al. PAX2 loss by immunohistochemistry occurs early and often in endometrial hyperplasia. Int J Gynecol Pathol. 2012;31(2):151.CrossRefGoogle Scholar
  12. 12.
    Jemal A, et al. Cancer statistics. CA Cancer J Clin. 2008;58(2):71–96.CrossRefGoogle Scholar
  13. 13.
    Balasubramaniam G, et al. Hospital-based study of endometrial cancer survival in Mumbai, India. Asian Pac J Cancer Prev. 2013;14(2):977–80.CrossRefGoogle Scholar
  14. 14.
    Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia. A long-term study of “untreated” hyperplasia in 170 patients. Cancer. 1985;56(2):403–12.CrossRefGoogle Scholar
  15. 15.
    Morice P, et al. Endometrial cancer. Lancet. 2016;387(10023):1094–108.CrossRefGoogle Scholar
  16. 16.
    Montgomery BE, Daum GS, Dunton CJ. Endometrial hyperplasia: a review. Obstet Gynecol Surv. 2004;59(5):368–78.CrossRefGoogle Scholar
  17. 17.
    Rouzbahman M. Biopsy interpretation of the uterine cervix and corpus. London: BMJ Publishing Group; 2015.CrossRefGoogle Scholar
  18. 18.
    Amant F, et al. Endometrial cancer. Lancet. 2005;366(9484):491–505.CrossRefGoogle Scholar
  19. 19.
    Emons G, et al. New WHO classification of endometrial hyperplasias. Geburtshilfe Frauenheilkd. 2015;75(02):135–6.CrossRefGoogle Scholar
  20. 20.
    Wong J, et al. Molecular pathogenesis of endometrial intraepithelial neoplasia: precursor to endometrial carcinoma. Gynecol Oncol. 2016;141:69–70.CrossRefGoogle Scholar

Copyright information

© Association of Gynecologic Oncologists of India 2019

Authors and Affiliations

  1. 1.Department of PathologyArmed Forces Medical CollegePuneIndia
  2. 2.Department of PathologyCH (SC)PuneIndia

Personalised recommendations