Hif-1α and IGF Expression in Endometrial Hyperplasia
DOI:
https://doi.org/10.12775/JEHS.2020.10.11.006Keywords
endometrial hyperplasia, IGF, Hif-1α, malignancyAbstract
The objective: to assess the effect of insulin resistance and hypoxia on the risk of endometrial hyperplasia development. The research was conducted on the base of Municipal Maternity House №5 (Odessa, Ukraine). The data obtained from the sample of 417 reproductive, perimenopausal, and postmenopausal age women who referred for medical care to the gynecological department, were analyzed. All the women under examination were carried out medical and diagnostic scraping of the uterine cavity. Results. The intensity of hypoxia increases with age and closely correlates (r=0,78) with the level of insulin resistance. IGF demonstrates reverse dynamics – its rates has been diminished with age (r=-0,63). Conclusion. It was demonstrated that insulin resistance and hypoxia play significant role in the pathogenesis of endometrial hyperplasia. Indices of IGF and HIF could be recommended as valuable biomarkers of prognosis in the case of endometrial hyperplasia.
References
Armstrong AJ, Hurd WW, Elguero S, Barker NM, Zanotti KM. Diagnosis and management of endometrial hyperplasia. J Minim Invasive Gynecol. 2012 Sep-Oct;19(5):562-71. doi: 10.1016/j.jmig.2012.05.009. Epub 2012 Aug 3. PMID: 22863972.
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 Mar 1;23(2):232-254. doi: 10.1093/humupd/dmw042. PMID: 27920066; PMCID: PMC5850217.
Mills AM, Longacre TA. Endometrial hyperplasia. Semin Diagn Pathol. 2010 Nov;27(4):199-214. doi: 10.1053/j.semdp.2010.09.002. PMID: 21309256.
Vetter MH, Smith B, Benedict J, Hade EM, Bixel K, Copeland LJ, Cohn DE, Fowler JM, O'Malley D, Salani R, Backes FJ. Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia. Am J Obstet Gynecol. 2020 Jan;222(1):60.e1-60.e7. doi: 10.1016/j.ajog.2019.08.002. Epub 2019 Aug 8. PMID: 31401259; PMCID: PMC7201377.
Travaglino A, Raffone A, Saccone G, Mollo A, De Placido G, Insabato L, Zullo F. Endometrial hyperplasia and the risk of coexistent cancer: WHO versus EIN criteria. Histopathology. 2019 Apr;74(5):676-687. doi: 10.1111/his.13776. Epub 2019 Feb 10. PMID: 30347477.
Travaglino A, Raffone A, Saccone G, Insabato L, Mollo A, De Placido G, Zullo F. Immunohistochemical predictive markers of response to conservative treatment of endometrial hyperplasia and early endometrial cancer: A systematic review. Acta Obstet Gynecol Scand. 2019 Sep;98(9):1086-1099. doi: 10.1111/aogs.13587. Epub 2019 Mar 18. PMID: 30793281.
Anastasiadis PG, Skaphida PG, Koutlaki NG, Galazios GC, Tsikouras PN, Liberis VA. Descriptive epidemiology of endometrial hyperplasia in patients with abnormal uterine bleeding. Eur J Gynaecol Oncol. 2000;21(2):131-4. PMID: 10843470.
On the pathogenesis of endometrial hyperplasia. Bishtavi A.Kh., Gornykh OA, Gulieva VN, Chikovani NG, Gogoladze Kh.T., Kostin A.Yu., Ivanov A.E. , Chabrov A.M., Solopova A.G., Tabakman Yu.Yu., Manukhin I.B. Tumors of the female reproductive system. 2012. No. 3-4. S. 108-112 (in Russian)
Lv Q, Yang B, Ning C, Xie B, Nie G, Chen X, Chen Q. Hypoxia is involved in the reduction of HtrA3 in patients with endometrial hyperplasia and cancer. Biochem Biophys Res Commun. 2018 Sep 18;503(4):2918-2923. doi: 10.1016/j.bbrc.2018.08.070. Epub 2018 Aug 20. PMID: 30139517.
Al-Sharaky DR, Abdou AG, Wahed MM, Kassem HA. HIF-1α and GLUT-1 Expression in Atypical Endometrial Hyperplasia, Type I and II Endometrial Carcinoma: A Potential Role in Pathogenesis. J Clin Diagn Res. 2016 May;10(5):EC20-7. doi: 10.7860/JCDR/2016/19576.7805. Epub 2016 May 1. PMID: 27437226; PMCID: PMC4948402.
Spirina LV, Yunusova NV, Kondakova IV, Kolomiets LA, Koval VD, Chernyshova AL, Shpileva OV. Association of growth factors, HIF-1 and NF-κB expression with proteasomes in endometrial cancer. Mol Biol Rep. 2012 Sep;39(9):8655-62. doi: 10.1007/s11033-012-1720-y. Epub 2012 Jun 19. PMID: 22711307.
Horrée N, van Diest PJ, van der Groep P, Sie-Go DM, Heintz AP. Hypoxia and angiogenesis in endometrioid endometrial carcinogenesis. Cell Oncol. 2007;29(3):219-27. doi: 10.1155/2007/434731. PMID: 17452774; PMCID: PMC4618415.
Endometrial hyperplasia: controversial issues of pathogenesis and therapy. Tabakman Yu.Yu., Solopova A.G., Bishtavi A.Kh., Idrisova L.E. Obstetrics, gynecology and reproduction. 2016.Vol. 10.No. 3.P. 5-10. (in Russian)
Yang B, Xie L, Zhang H, Zhu Q, Du Y, Luo X, Chen X. Insulin resistance and overweight prolonged fertility-sparing treatment duration in endometrial atypical hyperplasia patients. J Gynecol Oncol. 2018 May;29(3):e35. doi: 10.3802/jgo.2018.29.e35. Epub 2018 Feb 19. PMID: 29533020; PMCID: PMC5920219.
Etiology and pathogenesis of endometrial hyperplastic processes in postmenopausal women. Shakhlamova M.N., Isaeva E.A., Pankratov V.V. Questions of gynecology, obstetrics and perinatology. 2011. T. 10.No. 4. S. 76-84. (in Russian)
Flannery CA, Saleh FL, Choe GH, Selen DJ, Kodaman PH, Kliman HJ, Wood TL, Taylor HS. Differential Expression of IR-A, IR-B and IGF-1R in Endometrial Physiology and Distinct Signature in Adenocarcinoma. J Clin Endocrinol Metab. 2016 Jul;101(7):2883-91. doi: 10.1210/jc.2016-1795. Epub 2016 Apr 18. PMID: 27088794; PMCID: PMC4929835.
Kwasniewski W, Gozdzicka-Jozefiak A, Wolun-Cholewa M, Polak G, Sierocinska-Sawa J, Kwasniewska A, Kotarski J. Microsatellite polymorphism in the P1 promoter region of the IGF 1 gene is associated with endometrial cancer. Mol Med Rep. 2016 Jun;13(6):4950-8. doi: 10.3892/mmr.2016.5181. Epub 2016 Apr 25. PMID: 27121258; PMCID: PMC4878573.
Waksmański B, Dudkiewicz J, Dabrowski S. Function of insulin-like growth factor (IGF-I) and its binding protein (IGFBP-1) in pathological proliferation of endometrium. Wiad Lek. 2001;54(11-12):656-61. PMID: 11928553.
IGF-I: a mitogen also involved in differentiation processes in mammalian cells. Benito M., Valverde A.M., Lorenzo M. The International Journal of Biochemistry & Cell Biology. 1996. Т. 28. № 5. С. 499-510
Patent 130889 IPC G01N 33/48 (2006.01) G01N 33/49 (2006.01) G01N 33/50 (2006.01). Method for diagnosing the stage of development of the hyperplastic process of the endometrium in the perimenopausal period Application u 201807790 dated 12.07.2018. Inventor: Chumak Zinaida Vasylivna; Zelinsky Alexander Alekseevich; Shapoval Mykola Vitaliyovych. Copyright: Odessa International Medical University. Publ. 12/26/2018, bldg. № 24 (in Ukrainian)
HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) https://www.mdcalc.com/homa-ir-homeostatic-model-assessment-insulin-resistance
Make AI Real: Operationalize Data Science https://www.tibco.com/products/data-science
Downloads
Published
How to Cite
Issue
Section
License
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 437
Number of citations: 0
