Immunohistochemical features of cyclooxygenase-2 expression in endometrial hyperplasia without atypia

Authors

  • N. Ye. Horban National Academy of Medical Sciences of Ukraine", Kyiv, Ukraine,
  • T. D. Zadorozhna National Academy of Medical Sciences of Ukraine", Kyiv, Ukraine,
  • I. B. Vovk National Academy of Medical Sciences of Ukraine", Kyiv, Ukraine,
  • V. K. Kondratiuk National Academy of Medical Sciences of Ukraine", Kyiv, Ukraine,
  • S. M. Kilichevych the National Academy of Medical Sciences of Ukraine", Kyiv, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2019.4.173346

Keywords:

endometrial hyperplasia, cyclooxygenase-2, immunohistochemistry

Abstract

 

Hyperplastic processes of the endometrium without atypia have been an urgent problem for researchers around the world for a long time, given the current position of cancer alertness and violations of reproductive function.

Objective. To study immunohistochemically the expression level of the new biomarker - cyclooxygenase-2 (COX-2) in various types of endometrial hyperplasia without atypia in samples of altered endometrial tissue from 30 patients of reproductive age (39.47 ± 1.1 years).

Materials and methods. Endometrial hyperplasia manifested as glandular in 17 patients (56.7%), glandular-cystic - in 11 (36.7 %), stromal and cystic-atrophic forms – in one case for each form (3.3 %). The study was carried out according to the standardized protocol of primary monoclonal antibodies COX-2 manufacturer (Thermo Scientific, rabbit, working dilution 1:50-1:100) using the visualization system “UltraVision Quanto Detection System” of the Thermo Scientific company in paraffin sections. Samples were stained with methylene green and mounted using Canadian balsam. In this work we used the methods of optical light microscopy (Olympus BX 51,Japan) and immunohistochemistry. Localization of staining (gland/stroma) and intensity score were determined by the stain intensity (0 – no staining, 1 – weak, 2 – moderate, 3 – strong).

Results. The presence of COX-2 expression in the stromal component of the endometrial tissue samples was found from the majority of the examined patients (in 24 cases, 80.0%), however, its levels were recorded only as weakly positive. In glandular endometrial structures, in the presence of endometrial hyperplasia without atypia, the levels of COX-2 expression were characterized by some variability and dependence on structural localization. Thus, in 16 patients (66.7 %) its weakly positive expression was revealed, in 7 examined persons (29.2 %) – moderately stained material. Intensive COX-2 expression was determined in one case (4.1%). COX-2 expression in the hyperplastic endometrium was not detected in 6 samples (20.0%). Morphological signs of chronic endometritis were revealed in 9 investigated samples (30.0 %) – lymphoplasmacytic infiltration, altered pseudostratification of glandular epithelium, lysis of individual epithelial gland structures which were confirmed immunohistochemically: positive expression of CD138 in plasma cells.

Conclusions. The study data can serve as one of the criteria for the differential approach to a choice of treatment tactics in patients with a hyperproliferative endometrial pathology including prevention of possible malignant transformation.

References

American College of Obstetricians and Gynecologists (2015) Endometrial intraepithelial neoplasia. Committee Opinion. ACOG., 631, 1272–1278.

Emons, G., Beckmann, M. W., Schmidt D., & Mallmann, P. (2015) New WHO Classification of Endometrial Hyperplasias. Geburtshilfe Frauenheilkd, 75(2), 135–136. doi: 10.1055/s-0034-1396256

Vysotskaya, I. V., Letyagin, V. P., & Pogodina, E. M. (2017). Molekulyarnye osobennosti predopukholevoj patologii molochnykh zhelez [Molecular characteristics of premalignant breast lesions]. Sovremennaya Onkologiya, 19(1), 5–8. [in Russian].

Moore, K., & Brewer, M. A. (2017). Endometrial Cancer: Is This a New Disease? Am Soc Clin Oncol Educ Book, 37, 435–442. doi: 10.14694/EDBK_175666

Suri, V., & Arora, A. (2015). Management of Endometrial Cancer: A Review. Reviews on Recent Clinical Trials, 10(4). 309–16. doi: 10.2174/1574887110666150923115228

Janda, M., McGrath, S., & Obermair, A. (2018). Challenges and controversies in the conservative management of uterine and ovarian cancer. Best Pract Res Clin Obstet Gynaecol, 55, 93–108. doi: 10.1016/j.bpobgyn.2018.08.004

Hutt, S., Tailor, A., Ellis, P., Michael, A, Butler-Manuel, S., & Chatterjee, J. (2019). The role of biomarkers in endometrial cancer and hyperplasia: a literature review. Acta Oncol, 58(3), 342–352. doi: 10.1080/0284186X.2018.1540886

Sunita, B. S., Sen, A., & Suhag, V. (2018). To evaluate immunoreactivity of cyclooxygenase-2 in cases of endometrial carcinoma and correlate it with expression of p53 and vascular endothelial growth factor. J Cancer Res Ther, 14(6), 1366–1372. doi: 10.4103/0973-1482.202890

Liu, Y., Li, H., Zhao, C., & Jia, H. (2018). MicroRNA-101 inhibits angiogenesis via COX-2 in endometrial carcinoma. Mol Cell Biochem, 448(1–2), 61–69. doi: 10.1007/s11010-018-3313-0

Ma, X., Hui, Y., Lin, L., Wu, Y., Zhang, X., & Liu, P. (2015). Clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues. Pak J Med Sci., 31(2), 280–284. doi: 10.12669/pjms.312.6604

Kurumbail, R. G., Stevens, A. M., Gierse, J. K., McDonald, J. J., Stegeman, R. A., Pak, J. Y., et al. (1996). Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature, 384(6610), 644–648. doi: 10.1038/384644a0

Zelenay, S., Reis, E., & Sousa, C. (2016). Reducing prostaglandin E2 production to raise cancer immunogenicity. Oncoimmunology, 5(5), e1123370. doi: 10.1080/2162402X.2015.1123370

Cebola, I., & Peinado, M. A. (2012). Epigenetic deregulation of the COX pathway in cancer. Prog Lipid Res, 51(4), 301–13. doi: 10.1016/j.plipres.2012.02.00

Shevchenko, V. E., Taipov, M. A., Kovalev, S. V., Arnotskaya, N. E. Pavlova, O. M., Kudryavtsev, I. A., & Nikiforova, Z. N. (2012). Analiz belkov, associirovannykh s e'kspressiej ciklooksigenazy-2 i biosintezom PGE2 v kletkakh raka molochnoj zhelezy s raznym metastaticheskim potencialom [Analysis of proteins associated with the expression of cyclooxygenase-2 and the biosynthesis of PGE2 in breast cancer cells with different metastatic potential]. Opukholi zhenskoj reproduktivnoj sistemy, 3–4, 19–28 [in Russian].

St-Louis, I., Singh, M., Brasseur, K., Leblanc, V., Parent, S., & Asselin, E. (2010). Expression of COX-1 and COX-2 in the endometrium of cyclic, pregnant and in a model of pseudopregnant rats and their regulation by sex steroids. Reprod Biol Endocrinol, 8, 103. doi: 10.1186/1477-7827-8-103

Wang, Y., Qu, Y., & Song, W. (2015). Genetic variation in COX-2 -1195 and the risk of endometriosis and adenomyosis. Clin Exp Obstet Gynecol., 42(2), 168–172.

Pozharisski, K. M., Vinokurov, V. L., Zharinov, G. M., Boldaryan, N. A., Kuznetsova, M. Ye., Gasparyan, N. A., & Samsonova, Ye. A. (2008). Immunogistokhimicheskie markery v kachestve prognosticheskikh kriteriev v onkoginekologii [Immunohistochemical markers as prognosticators in oncogynecology]. Voprosy onkologii, 54(4), 463–469. [in Russian].

Wallace, A. E., Gibson, D. A., Saunders, P. T., & Jabbour, H. N. (2010). Inflammatory events in endometrial adenocarcinoma. J Endocrinol, 206(2), 141–157. doi: 10.1677/JOE-10-0072

Chishima, F., Hayakawa, S., Sugita, K., Kinukawa, N., Aleemuzzaman, S., Nemoto, N. et al. (2002). Increased expression of cyclooxygenase-2 in local lesions of endometriosis patients. Am. Journ. of reproductive immunology, 48(1), 50–56.

Stanoevich, I. (2009) Vliyanie selektivnogo ingibitora ciklooksigenazyi-2 celekoksiba na rezul'tativnost' gormonal'noj terapii bol'nykh s giperplaziej e'ndometriya [Effect of the selestive cyclooxygenase-2 inhibitor celecoxib on the effecttiveness of normal therapy in patiens with endometrial hyperplasia]. Vrach, 4, 47–49. [in Russian].

Orejuela, F. J., Ramondetta, L. M., Smith, J., Brown, J., Lemos, L. B., Li, Y., & Hollier, L. M. (2005). Estrogen and progesterone receptors and cyclooxygenase 2 expression in endometrial cancer, endometrial hyperplasia, and normal endometrium. Gynecol Oncol., 97(2), 483–488. doi: 10.1016/j.ygyno.2005.02.010

How to Cite

1.
Horban NY, Zadorozhna TD, Vovk IB, Kondratiuk VK, Kilichevych SM. Immunohistochemical features of cyclooxygenase-2 expression in endometrial hyperplasia without atypia. Zaporozhye Medical Journal [Internet]. 2019Jul.15 [cited 2024Dec.23];(4). Available from: http://zmj.zsmu.edu.ua/article/view/173346

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Original research