Pathology & Oncology Research

, Volume 25, Issue 2, pp 471–476 | Cite as

BCL-2 and PAX2 Expressions in EIN which Had Been Previously Diagnosed as Non-Atypical Hyperplasia

  • Levent TrabzonluEmail author
  • Bahar Muezzinoglu
  • Aydin Corakci
Original Article


The relationship between PAX2 and another anti-apoptotic gene, BCL-2, has been shown in a limited number of studies. The aims of this study are to investigate the value of PAX2 and BCL-2 expressions in lesions which have been defined as nonatypical hyperplasia in terms of detecting EIN and to evaluate the relations of these proteins in EIN. For this purpose, 108 cases of non-atypical endometrial hyperplasia diagnosed from 2006 to 2011 were re-evaluated. Immunohistochemical studies with PAX2 and BCL-2 were performed in 20 cases with EIN and 34 cases with benign hyperplasia. The mean BCL-2 immunohistochemistry scores of benign hyperplasia and EIN cases were 4.06 ± 1.04 and 4.63 ± 2.03, respectively. The mean BCL-2 score of EIN cases was significantly higher than benign hyperplasia (p = 0.021). The mean PAX2 scores of benign hyperplasia and EIN cases were 4.32 ± 1.07 and 2.19 ± 2.34, respectively. The mean PAX2 scores of EIN cases were significantly lower than benign hyperplasia (p = 0.001). BCL-2 expression was increased compared to normal endometrium in 66.7% of EIN cases, and PAX2 expression was decreased in 73.3%. Consistent with this, in 60% of cases, BCL-2 expression was increased compared to normal endometrium, while PAX2 expression was decreased. BCL-2 and PAX2 protein expression changes occur in early phases of endometrial tumorigenesis. These changes are often seen as a simultaneous increase in BCL-2 expression and decrease in PAX2 expression.


Endometrial intraepithelial neoplasia PAX2 BCL-2 Immunohistochemistry Uterus Endometrial hyperplasia 



This work was supported by a research grant (Project No: GO KAEK 2016/194) from the Kocaeli University Division of Scientific Research Projects (KOÜBAPB, abbreviation in Turkish).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Kurman RJ, Kaminski PF, Norris HJ (1985) The behavior of endometrial hyperplasia. A long-term study of “untreated” hyperplasia in 170 patients. Cancer 56:403–412CrossRefGoogle Scholar
  2. 2.
    Mutter GL, Baak JP, Crum CP et al (2000) Endometrial precancer diagnosis by histopathology, clonal analysis, and computerized morphometry. J Pathol 190:462–469.<462::AID-PATH590>3.0.CO;2-D CrossRefGoogle Scholar
  3. 3.
    Mutter GL, Chaponot ML, Fletcher JA (1995) A polymerase chain reaction assay for non-random X chromosome inactivation identifies monoclonal endometrial cancers and precancers. Am J Pathol 146:501–508Google Scholar
  4. 4.
    Baak JP, Mutter GL, Robboy SJ et al (2005) The molecular genetics and morphometry-based endometrial intraepithelial neoplasia classification system predicts disease progression in endometrial hyperplasia more accurately than the 1994 World Health Organization classification system. Cancer 103:2304–2312. CrossRefGoogle Scholar
  5. 5.
    Hecht JL, Mutter GL (2006) Molecular and pathologic aspects of endometrial carcinogenesis. J Clin Oncol 24:4783–4791. CrossRefGoogle Scholar
  6. 6.
    Tsujimoto Y, Finger LR, Yunis J et al (1984) Cloning of the chromosome breakpoint of neoplastic B cells with the t (14;18) chromosome translocation. Science 226:1097–1099CrossRefGoogle Scholar
  7. 7.
    Kapucuoglu N, Aktepe F, Kaya H et al (2007) Immunohistochemical expression of PTEN in normal, hyperplastic and malignant endometrium and its correlation with hormone receptors, bcl-2, bax, and apoptotic index. Pathol Res Pract 203:153–162. CrossRefGoogle Scholar
  8. 8.
    Kokawa K, Shikone T, Otani T, Nakano R (1999) Apoptosis and the expression of Bax and Bcl-2 in squamous cell carcinoma and adenocarcinoma of the uterine cervix. Cancer 85:1799–1809.<1799::AID-CNCR21>3.0.CO;2-M CrossRefGoogle Scholar
  9. 9.
    Vaskivuo TE, Stenbäck F, Tapanainen JS (2002) Apoptosis and apoptosis-related factors Bcl-2, Bax, tumor necrosis factor-α, and NF-κB in human endometrial hyperplasia and carcinoma. Cancer 95:1463–1471. CrossRefGoogle Scholar
  10. 10.
    Stuart ET, Gruss P (1996) PAX: developmental control genes in cell growth and differentiation. Cell Growth Differ 7:405–412Google Scholar
  11. 11.
    Stuart ET, Haffner R, Oren M, Gruss P (1995) Loss of p53 function through PAX-mediated transcriptional repression. EMBO J 14:5638CrossRefGoogle Scholar
  12. 12.
    Allison KH, Upson K, Reed SD et al (2012) PAX2 loss by immunohistochemistry occurs early and often in endometrial hyperplasia. Int J Gynecol Pathol 31:159–167. CrossRefGoogle Scholar
  13. 13.
    Quick CM, Laury AR, Monte NM, Mutter GL (2012) Utility of PAX2 as a marker for diagnosis of endometrial intraepithelial neoplasia. Am J Clin Pathol 138:678–684. CrossRefGoogle Scholar
  14. 14.
    Winyard PJ, Risdon RA, Sams VR et al (1996) The PAX2 transcription factor is expressed in cystic and hyperproliferative dysplastic epithelia in human kidney malformations. J Clin Invest 98:451–459. CrossRefGoogle Scholar
  15. 15.
    Zhang LP, Shi XY, Zhao CY et al (2011) RNA interference of pax2 inhibits growth of transplanted human endometrial cancer cells in nude mice. Chin J Cancer 30:400–406CrossRefGoogle Scholar
  16. 16.
    Mutter GL (2002) Diagnosis of premalignant endometrial disease. J Clin Pathol 55:326–331CrossRefGoogle Scholar
  17. 17.
    Zaino RJ, Carinelli S, Ellenson LH, et al (2014) Tumours of the uterine corpus: epithelial tumours and precursors. In: Kurman RJ, Carcangiu M, Herrington C, Young R (eds) WHO Classif. Tumours female Reprod. Organs, 4th ed. WHO Press, Lyon, pp 125–126Google Scholar
  18. 18.
    Hecht JL, Ince T, Baak JP et al (2005) Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis. Mod Pathol 18:324–330. CrossRefGoogle Scholar
  19. 19.
    Popat VC, Vora DN, Gadhvi NS et al (2010) Comparison of endometrial intraepithelial neoplasia with WHO endometrial hyperplasia classification system. A comparative study of 150 cases. Histopathology 57:646–648. CrossRefGoogle Scholar
  20. 20.
    Allred DC, Harvey JM, Berardo M, Clark GM (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11:155–168Google Scholar
  21. 21.
    Bissonnette RP, Echeverri F, Mahboubi A, Green DR (1992) Apoptotic cell death induced by c-myc is inhibited by bcl-2. Nature 359:552–554. CrossRefGoogle Scholar
  22. 22.
    Hemann MT, Lowe SW (2006) The p53–Bcl-2 connection. Cell Death Differ 13:1256–1259. CrossRefGoogle Scholar
  23. 23.
    Bozkurt KK, Yalcin Y, Erdemoglu E et al (2016) The role of immunohistochemical adrenomedullin and Bcl-2 expression in development of type-1 endometrial adenocarcinoma Adrenomedullin expression in endometrium. Pathol Res Pract 212:450–455. CrossRefGoogle Scholar
  24. 24.
    Amalinei C, Cianga C, Balan R et al (2011) Immunohistochemical analysis of steroid receptors, proliferation markers, apoptosis related molecules, and gelatinases in non-neoplastic and neoplastic endometrium. Ann Anat - Anat Anzeiger 193:43–55. CrossRefGoogle Scholar
  25. 25.
    Wu H, Chen Y, Liang J et al (2005) Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature 438:981–987. CrossRefGoogle Scholar
  26. 26.
    Strissel PL, Ellmann S, Loprich E et al (2008) Early aberrant insulin-like growth factor signaling in the progression to endometrial carcinoma is augmented by tamoxifen. Int J Cancer 123:2871–2879. CrossRefGoogle Scholar
  27. 27.
    Kahraman K, Kiremitci S, Taskin S et al (2012) Expression pattern of PAX2 in hyperplastic and malignant endometrium. Arch Gynecol Obstet 286:173–178. CrossRefGoogle Scholar
  28. 28.
    Joiner AK, Quick CM, Jeffus SK (2015) Pax2 expression in simultaneously diagnosed WHO and EIN classification systems. Int J Gynecol Pathol 34:40–46. CrossRefGoogle Scholar

Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Levent Trabzonlu
    • 1
    Email author
  • Bahar Muezzinoglu
    • 2
  • Aydin Corakci
    • 3
  1. 1.Department of PathologyJohns Hopkins School of MedicineBaltimoreUSA
  2. 2.Department of PathologyKocaeli University School of MedicineKocaeliTurkey
  3. 3.Department of Gynecology and ObstetricsKocaeli University School of MedicineKocaeliTurkey

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