Generic placeholder image

Current Women`s Health Reviews

Editor-in-Chief

ISSN (Print): 1573-4048
ISSN (Online): 1875-6581

Research Article

Possible Role of PTEN Expression in Discriminating Benign Endometrial Hyperplasia from Atypical Hyperplasia/Endometrial Intraepithelial Neoplasia in a Series of Egyptian Patients

Author(s): Nevine I. Ramzy, Wael S. Ibrahiam, Hanan H.M. Ali, Mona M.A. Akle and Sara E. Khalifa*

Volume 18, Issue 3, 2022

Published on: 17 December, 2021

Article ID: e031121195558 Pages: 6

DOI: 10.2174/1573404817666210811125751

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Endometrial hyperplasia represents a heterogeneous group of lesions in response to the unopposed growth-promoting action of estrogen. WHO classified endometrial hyperplastic lesions into Benign Hyperplasia (BH) and atypical hyperplasia/ endometrial intraepithelial neoplasia AH/EIN. Phosphatase and tensin homolog (PTEN) is one of the earliest and most common genetic abnormalities detected in endometrioid adenocarcinoma (type I) and even in its precursors. This study aims at histological evaluation of hyperplastic endometrial lesions according to WHO 2014 and investigates the role of PTEN expression in highlighting the precancerous group (AH/EIN).

Patient and Methods: This study included a series of 70 Egyptian patients who suffered from hyperplastic endometrial lesions. They were previously diagnosed according to WHO 1994 schema simple endometrial hyperplasia without atypia (n=18), simple endometrial hyperplasia with atypia (n=2), complex hyperplasia without atypia (n=25), complex hyperplasia with atypia (n=5) and hyperplastic endometrial polyps (n=20).

Results: Cases were histologically re-evaluated according to WHO 2014 classification; BH (62 cases) and eight cases of AH/EIN. A significant difference in PTEN expression (regarding percentage and intensity of staining) in relation to histopathological diagnosis was detected (P-value 0.02 and <0.05, respectively). The sensitivity and specificity of the absence of diffuse PTEN protein expression (>50%) to detect AH/EIN were 100% and 77.4%, respectively.

Conclusion: Diffuse, dim or loss of immunohistochemical expression of PTEN protein is significantly correlated with the new WHO classification segregation of AH/EIN as precancerous lesions. However, further studies are recommended to confirm this association.

Keywords: Benign endometrial hyperplasia, AH/ EIN, WHO 2014, PTEN, proliferation of endometrium, precancerous lesions.

Graphical Abstract
[1]
Sanderson PA, Critchley HO, Williams AR, Arends MJ, Saunders PT. New concepts for an old problem: The diagnosis of endometrial hyperplasia. Hum Reprod Update 2017; 23(2): 232-54.
[PMID: 27920066]
[2]
Committee on Gynecologic Practice. The American College of Obstetricians and Gynecologists Committee Opinion no. 631. Endometrial intraepithelial neoplasia. Obstet Gynecol 2015; 125(5): 1272-8.
[http://dx.doi.org/10.1097/01.AOG.0000465189.50026.20] [PMID: 25932867]
[3]
Sobczuk K, Sobczuk A. New classification system of endometrial hyperplasia WHO 2014 and its clinical implications. Przegl Menopauz 2017; 16(3): 107-11.
[http://dx.doi.org/10.5114/pm.2017.70589] [PMID: 29507578]
[4]
Moore E, Shafi M. Endometrial hyperplasia. Obstetrics, Gynaecol Reprod Med 2013; 23: 3.
[http://dx.doi.org/10.1016/j.ogrm.2013.01.002]
[5]
Owings RA, Quick CM. Endometrial intraepithelial neoplasia. Arch Pathol Lab Med 2014; 138(4): 484-91.
[http://dx.doi.org/10.5858/arpa.2012-0709-RA] [PMID: 24678678]
[6]
Zaino R, Carinelli SG, Ellenson LH, et al. Tumors of the uterine corpus: epithelial tumors and precursors.WHO Classification of tumors of female reproductive organs. 4th. Lyon: WHO Press 2014; pp. 125-6.
[7]
Djordjevic B, Hennessy BT, Li J, et al. Clinical assessment of PTEN loss in endometrial carcinoma: immunohistochemistry outperforms gene sequencing. Mod Pathol 2012; 25(5): 699-708.
[http://dx.doi.org/10.1038/modpathol.2011.208] [PMID: 22301702]
[8]
Monte NM, Webster KA, Neuberg D, Dressler GR, Mutter GL. Joint loss of PAX2 and PTEN expression in endometrial precancers and cancer. Cancer Res 2010; 70(15): 6225-32.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-0149] [PMID: 20631067]
[9]
Scully RE, Bonfiglio TA, Kurman RJ, et al. Histological typing of female genital tract tumours. Heidelberg, Berlin, Germany: Springer 1994; pp. 1-189.
[http://dx.doi.org/10.1007/978-3-642-85014-1]
[10]
Sarmadi S, Izadi-Mood N, Sotoudeh K, Tavangar SM. Altered PTEN expression; a diagnostic marker for differentiating normal, hyperplastic and neoplastic endometrium. Diagn Pathol 2009; 4: 41.
[http://dx.doi.org/10.1186/1746-1596-4-41] [PMID: 19930726]
[11]
Zhang HY, Liang F, Jia ZL, Song ST, Jiang ZF. PTEN mutation, methylation and expression in breast cancer patients. Oncol Lett 2013; 6(1): 161-8.
[http://dx.doi.org/10.3892/ol.2013.1331] [PMID: 23946797]
[12]
Mishra S, Singh U, Quereshi S, et al. Clinicopathological profile of endometrial Hyperplasia and endometrial carcinoma. GJRA 2016; 5: 521-4.
[13]
van der Putten LJM, van Hoof R, Tops BBJ, et al. Molecular profiles of benign and (pre)malignant endometrial lesions. Carcinogenesis 2017; 38(3): 329-35.
[http://dx.doi.org/10.1093/carcin/bgx008] [PMID: 28203752]
[14]
Mutter GL. Endometrial intraepithelial neoplasia (EIN): will it bring order to chaos? The Endometrial Collaborative Group. Gynecol Oncol 2000; 76(3): 287-90.
[http://dx.doi.org/10.1006/gyno.1999.5580] [PMID: 10684697]
[15]
Gallos ID, Alazzam M, Clark T, et al. RCOG green-top guideline: management of endometrial hyperplasia. 2016. Available from: https://www.rcog.org.uk/globalassets/documents/guidelines/green-top-guidelines/gtg_ 67_endometrial_hyperplasia.pdf
[16]
Semere LG, Ko E, Johnson NR, et al. Endometrial intraepithelial neoplasia: clinical correlates and outcomes. Obstet Gynecol 2011; 118(1): 21-8.
[http://dx.doi.org/10.1097/AOG.0b013e31821d78af] [PMID: 21691159]
[17]
Goncharenko VM, Beniuk VA, Kalenska OV, Demchenko OM, Spivak MY, Bubnov RV. Predictive diagnosis of endometrial hyperplasia and personalized therapeutic strategy in women of fertile age. EPMA J 2013; 4(1): 24-44.
[http://dx.doi.org/10.1186/1878-5085-4-24] [PMID: 24314145]
[18]
Hecht JL, Ince TA, Baak JPA, et al. Prediction of endometrial carcinoma by subjective EIN diagnosis. Mod Pathol 2005; 18: 324-30.
[http://dx.doi.org/10.1038/modpathol.3800328] [PMID: 15529181]
[19]
Salman MC, Usubutun A, Boynukalin K, Yuce K. Comparison of WHO and endometrial intraepithelial neoplasia classifications in predicting the presence of coexistent malignancy in endometrial hyperplasia. J Gynecol Oncol 2010; 21(2): 97-101.
[http://dx.doi.org/10.3802/jgo.2010.21.2.97] [PMID: 20613899]
[20]
Sirimusika N, Peeyananjarassri K, Suphasynth Y, Wootipoom V, Kanjanapradit K, Geater A. Management and clinical outcomes of endometrial hyperplasia during a 13-year period in Songklanagarind Hospital. J Med Assoc Thai 2014; 97(3): 260-6.
[PMID: 25123004]
[21]
Byun JM, Jeong DH, Kim YN, et al. Endometrial cancer arising from atypical complex hyperplasia: The significance in an endometrial biopsy and a diagnostic challenge. Obstet Gynecol Sci 2015; 58(6): 468-74.
[http://dx.doi.org/10.5468/ogs.2015.58.6.468] [PMID: 26623410]
[22]
Lortet-Tieulent J, Ferlay J, Bray F, Jemal A. International patterns and trends in endometrial cancer incidence, 1978-2013. J Natl Cancer Inst 2018; 110(4): 354-61.
[http://dx.doi.org/10.1093/jnci/djx214] [PMID: 29045681]
[23]
Mutter GL, Monte NM, Neuberg D, Ferenczy A, Eng C. Emergence, involution, and progression to carcinoma of mutant clones in normal endometrial tissues. Cancer Res 2014; 74(10): 2796-802.
[http://dx.doi.org/10.1158/0008-5472.CAN-14-0108] [PMID: 24662919]
[24]
Garg K, Broaddus RR, Soslow RA, Urbauer DL, Levine DA, Djordjevic B. Pathologic scoring of PTEN immunohistochemistry in endometrial carcinoma is highly reproducible. Int J Gynecol Pathol 2012; 31(1): 48-56.
[http://dx.doi.org/10.1097/PGP.0b013e3182230d00] [PMID: 22123723]
[25]
Raffone A, Travaglino A, Saccone G, et al. Loss of PTEN expression as diagnostic marker of endometrial precancer: A systematic review and meta-analysis. Acta Obstet Gynecol Scand 2019; 98(3): 275-86.
[http://dx.doi.org/10.1111/aogs.13513]
[26]
Travaglino A, Raffone A, Saccone G, et al. Complexity of glandular architecture should be reconsidered in the classification and management of endometrial hyperplasia. APMIS 2019; 127(6): 427-34.
[http://dx.doi.org/10.1111/apm.12945] [PMID: 30802329]
[27]
Abrão F, Modotti WP, Spadoto-Dias D, et al. Concomitant p53 and PTEN immunoexpression to predict the risk of malignancy in endometrial polyps. Medicine (Baltimore) 2018; 97(38): e12304.
[http://dx.doi.org/10.1097/MD.0000000000012304] [PMID: 30235677]
[28]
Devic A, Vasiljevic M, Devic A. Endoemtrial intraepithelial neoplasia in an endometrial polyp. Serb J Exp Clin Res 2015; 16: 343-6.
[http://dx.doi.org/10.1515/sjecr-2015-0042]
[29]
Lenci MA, Nascimento VAL, Grandini AB, et al. Premalignant and malignant lesions in endometrial polyps in patients undergoing hysteroscopic polypectomy. Einstein (Sao Paulo) 2014; 12(1): 16-21.
[http://dx.doi.org/10.1590/S1679-45082014AO2764] [PMID: 24728240]
[30]
Kurdoglu M, Kucukaydin Z, Kurdoglu Z, et al. Expression of laminin receptor 1 in normal, hyperplastic, and malignant endometrium. Int J Gynecol Pathol 2019; 38(4): 326-34.
[31]
Esmaieli HA, Amidfar H, Mostafidi E, et al. Study of the prognostic value of p53 and PTEn immunomarkers for endometrial cancer using immunohistochemistry. J Anal Res Clin Med 2017; 112-7.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy