Comparison of immunohistochemical characteristics of prognostic markers expression in non-metastatic and metastatic invasive endometrioid endometrial carcinoma
DOI:
https://doi.org/10.14739/2310-1210.2016.5.82627Keywords:
Endometrial Neoplasms, Estrogen Receptors, Progesterone Receptors, Tumor Suppressor Protein p53, Cyclin-Dependent Kinase Inhibitor p16, Ki-67 Antigen, Caspase 3, Matrix Metalloproteinase 9, TIMP1 Protein, HumanAbstract
Endometrial cancer occupies the sixth place among oncological morbidity structure in women worldwide.
The aim. To compare the expression levels of estrogene receptors – α and progesterone receptors, regulatory proteins p16 and p53, a marker of proliferation Ki-67 and the apoptotic degradation enzyme caspase-3, matrix metalloproteinase 9 (MMP 9) and its tissue inhibitor TIMP-1 in tumor and stromal cells of the invasive non-metastatic endometrioid endometrial carcinoma and also in invasive metastatic endometrioid endometrial carcinoma.
Materials and methods: Immunohistochemical and morphometric study of invasive non-metastatic рТ1-4N0Mx endometrioid endometrial carcinoma (n=56; age 42-83 years), invasive metastatic рТ1-4N1-2Mx endometrioid endometrial carcinoma (n=30; age 48-79 years) was performed.
Results: Statistically significantly higher expression level of estrogen receptor-α was detected in tumor cells of endometrioid endometrial carcinoma with metastasis to the regional lymph nodes in comparison with the expression level of these receptors in tumor cells of non-metastatic endometrioid endometrial carcinoma. The progesterone receptors expression levels in the tumor and stromal cells of invasive endometrioid endometrial carcinoma with metastasis to regional lymph nodes were lower in comparison with the corresponding expression levels of progesterone receptor in corresponding cells of non-metastatic endometrioid endometrial carcinoma. In stromal cells of endometrioid endometrial carcinoma with metastasis to the regional lymph nodes the expression level of caspase-3 was significantly lower too in comparison with the expression level of this enzyme in stromal cells of non-metastatic endometrioid endometrial carcinoma. In tumor and stromal cells of endometrioid endometrial carcinoma with metastasis to the regional lymph nodes the expression levels of MMP-9 and TIMP-1 are decreased significantly compared to the expression level of these markers in the respective cells of non-metastatic endometrioid endometrial carcinoma.
Conclusions. The expression level of estrogen receptor-α in the tumor cells was higher, the expression level of caspase 3 in stromal cells was lower and the expression levels of progesterone receptors, MMP 9 and TIMP-1 in tumor and stromal cells were lower in metastatic endometrioid endometrial carcinoma compared to non-metastatic endometrioid endometrial carcinoma. The obtained data can be used for individual prediction of metastasis to regional lymph nodes in patients with endometrioid endometrial carcinoma.
References
Stewart, B. W., & Wild, Ch. P. (2014). World cancer report 2014: IARC. Geneva: WHO Press.
Colombo, N., Creutzberg, C., Amant, F., Bosse, T., González-Martín, A., Ledermann, J., et al. (2016). ESMO-ESGO-ESTRO Consensus Conference on Endometrial Cancer. Diagnosis, Treatment and Follow-up. International Journal of Gynecologic Cancer, 26(1), 1–30.
Zidan, A. A., Hassan, A. A., Seadah, Sh. Sh. A., Ibrahim, E. H., & Attiah, S. M. (2015). Selected immunohistochemical prognostic factors in endometrial hyperplasia versus carcinoma. Journal of American Science, 11(4), 14–22.
Stanescu, A. D., Nistor, I., Poteca, A. G., Ditescu, D., & Comanescu, М. (2014). Prognostic biomarkers in endometrial adenocarcinoma. Romanian Journal of Morphology and Embryology, 55(4), 1339–1344.
Zhang, Y., Zhao, D., Gong, C., Zhang, F., He, J., Zhang, W., et al. (2015). Prognostic role of hormone receptors in endometrial cancer: a systematic review and meta-analysis. Journal of Surgical Oncology, 25(13), 208. doi: 10.1186/s12957-015-0619-1.
Gottwald, L., Kubiak, R., Pasz-Walczak, G., Sek, P., Piekarski, J., Szwalski, J., et al. (2013). The value of progesterone and estrogen receptors expression in tissue microarray method in prognosis of patients with endometrioid endometrial cancer. Ginekologia Polska, 84(2), 95–101.
Bender, D., Buekers, T., & Leslie, K.K. (2011). Hormone receptors and endometrial cancer. Proceedings in Obstetrics and Gynecology, 2(1), 1–25.
Makhina, E. V., Pichigina, A. K., Koldysheva, E. V., Molodykh, O. P., & Lushnikova, E. L. (2014). Diagnosticheskaya i prognosticheskaya znachimost' ocenki proliferativnoj aktivnosti kletochnykh populyacij e´ndometriya pri giperplasticheskikh i neoplasticheskikh processakh (obzor literatury) [Diagnostic and prognostic value of assessment of endometrial cell proliferative activity in hyperplastic and neoplastic processes (Review)]. Fundamental'nye issledovaniya, 10, 420–427. [in Russian].
Yu, Fang, Jiang, Qingping, Zhou, Ying, Yang, Zhen, Yu, Xiaoli, Wang, Hao, et al. (2012). Abnormal expression of matrix metalloproteinase-9 (MMP9) correlates with clinical course in Chinese patients with endometrial cancer. Journal: Disease Markers, 32(5), 321–327. doi: 10.3233/DMA-2011-0886.
Jong-Ryeol, Choi, Tae-Hwa, Lee, Young-Lim, Oh, Chun-Jun, Lee, & Won-Gyu, Kim. (2008). Expressions of MMP-2, MMP-9, TIMP-1, and TIMP-2 as prognostic factors in endometrial cancer. Korean Journal of Gynecological Oncology, 19(1), 57–67. http://dx.doi.org/10.3802/kjgo.2008.19.1.57.
Dabbs, D. J. (Ed.) (2010). Diagnostic Immunohistochemistry. Philadelphia: Saunders/Elsevier.
Allred, D. C., Harvey, J. M., Berardo, M., & Clark, G. M. (1998). Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Modern Pathology, 11, 155–168.
Risberg, B., Karlsson, K., Abeler, V., Lagrelius, A., Davidson, B., & Karlsson, M. G. (2002). Dissociated expression of Bcl-2 and Ki-67 in endometrial lesions: diagnostic and histogenetic implications. International Journal of Gynecological Pathology, 21(2), 155–160.
Buchynska, L. G., & Nesina, I. P. (2006). Expression of the cell cycle regulators p53, p21WAF1/CIP1 and p16INK4A in human endometrial adenocarcinoma. Experimental Oncology, 28(2), 152–155.
Tumanskyi, V. O., Yevsieiev, A. V., Kovalenko, I. S., & Zubko, M. D. (patentee) (2015) Patent Ukrainy na korysnu model №99314 Ukrayina, MPK (2015) G01N 21/00, G06K 9/00. Sposib fototsyfrovoi morfometrii imunohistokhimichnykh preparativ №u 2014 14 103 [Ukraine patent for utility model №99314 Ukraine, IPC (2015) G01N 21/00, G06K 9/00. Method of photo digital morphometrical study of immunohistochemical micropreparations]. Biuleten, 10. [in Ukrainian].
Rasband, W. S., & Image J, U. S. (1997–2016). National Institutes of Health. Bethesda, Maryland. – Retrieved from http://imagej.nih.gov/ij/.
Tumanskiy, V. A., & Chepets, V. A. (2016). Sravnitel'naya immunogistokhimicheskaya kharakteristika e´kspressii receptorov e´strogena-α i progesterona, r16 i r53, Ki-67 i kaspazy 3 v invazivnoj e´ndometrioidnoj adenokarcinome tela matki i v proliferativnom e´ndometrii [Comparison of immunohistochemical characteristics of expression estrogen receptors-alpha, progesterone receptors, p16, p53, Ki-67 and caspase 3 in invasive endometrial adenocarcinoma and normal proliferative endometrium]. Pathologia, 1(36), 22–28. doi: 10.14739/2310-1237.2016.1.72165.
Yang, T., Zhang, H., Qiu, H., Li, B., Wang, J., Du, G., et al. (2016). EFEMP1 is repressed by estrogen and inhibits the epithelial-mesenchymal transition via Wnt/β-catenin signaling in endometrial carcinoma. Oncotarget, 7(18), 25712–25. doi: 10.18632/oncotarget.8263.
Guo, Z. L., Guo, Z. L., Chen, K., Wang, X. Q., & Hu, W. (2011). Expression and relationship of Ezh2, Runx3 and caspase-3 in endometrial adenocarcinoma. Zhonghua Bing Li Xue Za Zhi, 40(6), 387–391.
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
