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Ayhan A, Mao TL, Suryo Rahmanto Y, et al. Increased proliferation in atypical hyperplasia/endometrioid intraepithelial neoplasia of the endometrium with concurrent inactivation of ARID1A and PTEN tumour suppressors. J Pathol Clin Res. 2015;1(3):186-93doi: 10.1002/cjp2.22.
Ayhan, A., Mao, T. L., Suryo Rahmanto, Y., Zeppernick, F., Ogawa, H., Wu, R. C., Wang, T. L., & Shih, I. e. M. (2015). Increased proliferation in atypical hyperplasia/endometrioid intraepithelial neoplasia of the endometrium with concurrent inactivation of ARID1A and PTEN tumour suppressors. The journal of pathology. Clinical research, 1(3), 186-93. https://doi.org/10.1002/cjp2.22
Ayhan, Ayse, et al. "Increased proliferation in atypical hyperplasia/endometrioid intraepithelial neoplasia of the endometrium with concurrent inactivation of ARID1A and PTEN tumour suppressors." The journal of pathology. Clinical research vol. 1,3 (2015): 186-93. doi: https://doi.org/10.1002/cjp2.22
Ayhan A, Mao TL, Suryo Rahmanto Y, Zeppernick F, Ogawa H, Wu RC, Wang TL, Shih IeM. Increased proliferation in atypical hyperplasia/endometrioid intraepithelial neoplasia of the endometrium with concurrent inactivation of ARID1A and PTEN tumour suppressors. J Pathol Clin Res. 2015 May 27;1(3):186-93. doi: 10.1002/cjp2.22. eCollection 2015 Jul. PMID: 27499903; PMCID: PMC4939882.
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J Pathol Clin Res. 2015 May 27;1(3):186-93. doi: 10.1002/cjp2.22. eCollection 2015 Jul.

Increased proliferation in atypical hyperplasia/endometrioid intraepithelial neoplasia of the endometrium with concurrent inactivation of ARID1A and PTEN tumour suppressors.

The journal of pathology. Clinical research

Ayse Ayhan, Tsui-Lien Mao, Yohan Suryo Rahmanto, Felix Zeppernick, Hiroshi Ogawa, Ren-Chin Wu, Tian-Li Wang, Ie-Ming Shih

Affiliations

  1. Department of PathologyJohns Hopkins Medical InstitutionsBaltimoreMaryland; Department of PathologyHamamatsu University School of Medicine and Seirei Mikatahara HospitalHamamatsuJapan.
  2. Department of Pathology National Taiwan University College of Medicine Taipei Taiwan.
  3. Department of Pathology Johns Hopkins Medical Institutions Baltimore Maryland.
  4. Department of PathologyJohns Hopkins Medical InstitutionsBaltimoreMaryland; Department of Gynecology and ObstetricsUniversity Hospital AachenGermany.
  5. Department of Pathology Hamamatsu University School of Medicine and Seirei Mikatahara Hospital Hamamatsu Japan.
  6. Department of PathologyJohns Hopkins Medical InstitutionsBaltimoreMaryland; Department of PathologyChang Gung Memorial Hospital and Chang Gung University College of MedicineTaoyuanTaiwan.
  7. Department of PathologyJohns Hopkins Medical InstitutionsBaltimoreMaryland; Department of Gynecology and ObstetricsJohns Hopkins Medical InstitutionsBaltimoreMaryland.

PMID: 27499903 PMCID: PMC4939882 DOI: 10.1002/cjp2.22

Abstract

Uterine endometrioid carcinoma is the most common neoplastic disease in the female genital tract and develops from a common precursor lesion, atypical hyperplasia/endometrioid intraepithelial neoplasia (AH/EIN). Although the genomic landscape of endometrioid carcinoma has been recently revealed, the molecular alterations that contribute to tumour progression from AH/EIN to carcinoma remain to be elucidated. In this study, we used immunohistochemistry to determine if loss of expression of two of the most commonly mutated tumour suppressors in endometrioid carcinoma, PTEN and ARID1A, was associated with increased proliferation in AH/EIN. We found that 80 (70%) of 114 cases exhibited decreased or undetectable PTEN and 17 (15%) of 114 cases had focal loss of ARID1A staining. ARID1A loss was focal, while PTEN loss was diffuse, and all specimens with ARID1A loss had concurrent PTEN loss (p = 0.0003). Mapping the distribution of PTEN and ARID1A staining in the same specimens demonstrated that all AH/EIN areas with ARID1A loss were geographically nested within the areas of PTEN loss. A significant increase in the proliferative activity was observed in areas of AH/EIN with concurrent loss of PTEN and ARID1A compared to immediately adjacent AH/EIN areas showing only PTEN loss. In a cell culture system, co-silencing of ARID1A and PTEN in human endometrial epithelial cells increased cellular proliferation to a greater degree than silencing either ARID1A or PTEN alone. These results suggest an essential gatekeeper role for ARID1A that prevents PTEN inactivation from promoting cellular proliferation in the transition of pre-cancerous lesions to uterine endometrioid carcinoma.

Keywords: ARID1A; PTEN; atypical hyperplasia; co‐silencing; endometrioid intraepithelial neoplasia; immunohistochemistry; in vitro cell culture model; proliferation; tumour suppressor

References

  1. Cancer Biol Ther. 2014 Jun 1;15(6):655-64 - PubMed
  2. Science. 2010 Oct 8;330(6001):228-31 - PubMed
  3. Neoplasia. 2012 Oct;14(10):986-93 - PubMed
  4. J Pathol. 2003 Apr;199(4):471-8 - PubMed
  5. Clin Cancer Res. 2001 Apr;7(4):892-5 - PubMed
  6. J Natl Cancer Inst. 2000 Jun 7;92 (11):924-30 - PubMed
  7. Lancet Oncol. 2014 Jun;15(7):e268-78 - PubMed
  8. Histopathology. 2013 Jan;62(1):111-23 - PubMed
  9. Am J Surg Pathol. 2011 May;35(5):625-32 - PubMed
  10. Int J Gynecol Pathol. 2007 Apr;26(2):103-14 - PubMed
  11. Mod Pathol. 2012 May;25(5):699-708 - PubMed
  12. Cancer Res. 2014 May 15;74(10 ):2796-802 - PubMed
  13. J Natl Cancer Inst. 2014 Jun 04;106(7):null - PubMed
  14. J Gynecol Oncol. 2013 Oct;24(4):376-81 - PubMed
  15. Oncogene. 2004 Jan 15;23 (2):617-28 - PubMed
  16. Int J Gynecol Cancer. 2012 Oct;22(8):1310-5 - PubMed
  17. Cancer Res. 2001 Jun 1;61(11):4311-4 - PubMed
  18. Cancer Res. 2011 Nov 1;71(21):6718-27 - PubMed
  19. N Engl J Med. 2010 Oct 14;363(16):1532-43 - PubMed
  20. Clin Cancer Res. 2011 Oct 15;17 (20):6563-73 - PubMed
  21. Nature. 2013 May 2;497(7447):67-73 - PubMed
  22. Am J Surg Pathol. 2013 Sep;37(9):1342-8 - PubMed

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