Immunohistochemical characterization of the expression of matrix metalloproteinase - 9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in the invasive endometrioid endometrial carcinoma

Authors

  • A. V. Chepets Zaporizhzhia State Medical University,

DOI:

https://doi.org/10.14739/2310-1237.2015.3.55613

Keywords:

Carcinoma Of Endometrium, MMP-9, TIMP-1

Abstract

Endometrial carcinoma is the most common gynecological malignancy in developed countries.

Aim. With the aim to determine MMP-9 and TIMP-1 expression levels in the invasive endometrioid endometrial carcinoma (EEC) cells and areas of the immunopositive cells in the center of the tumor and in the area of tumor invasion into the myometrium pathohistological, immunohistochemical and morphometric study of histological specimens of operative material of 56 women with pT1-4 stage of tumor was performed.

Methods and results. It was found that MMP-9 and TIMP-1 expression occurs in 100% of invasive EEC. The ММР-9 expression level in the cytoplasm of tumor cells is high – 129.11±2.38 CUOD, which is 2,2 times more than its level in normal proliferative endometrium – 59.45±9.58 CUOD (p <0.05 ). The TIMP-1 expression level is 9.58±2.68 CUOD that is 2.69 times more than the expression level of TIMP-1 in normal proliferative endometrium (3.56±0.35 CUOD, p <0.05) . MMP-9 immunopositive cells make up 50.78±0.91% of area of invasive EEC tissue section and TIMP-1 immunopositive cells make up 3.76±0.15% of area of tumor tissue section. That is statistically significantly more than in normal proliferative endometrium, which has 23.31±1.31% of ММР-9 immunopositive cells and 2.82±0.14% of TIMP-1 immunopositive cells of endometrial glands. Differences between high levels of MMP-9 in the center of EEC and in the tumor myometrial invasion zone, as well as differences between the very low expression levels of TIMP-1 in these regions of the tumor were not statistically significant. With increasing of EEC histological grade the MMP-9 and TIMP-1 expression levels significantly increase (p <0.05). There is direct weak correlation between the MMP-9 and TIMP-1 expression levels in the cells of EEC (Pearson coefficient r =+0.31). Direct strong correlation between the expression level of MMP-9 in the tumor cells and the grade of tumor (Pearson coefficient r =+0.71) is revealed.

Conclusion. The results of the study showed the increasing invasive capacity of EAE with the tumor grade increasing.

References

Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., Murray, T., & Thun, M. J. (2008) Cancer Statistics, 2008. CA: A Cancer Journal for Clinicians, 58(2), 71–96. doi: 10.3322/CA.2007.0010.

Aglund, K., Rauvala, M., Puistola, U., Angstrom, T., Turpeenniemi-Hujanen, T., Zackrission, B., Stendahl, U. (2004) Gelatinases A and B (MMP-2 and MMP9) in endometrial cancer – MMP9 correlates to the grade and the stage. Gynecol Oncol, 94, 699–704. doi: http://dx.doi.org/10.1016/j.ygyno.2004.06.028.

Di Nezza, L., Misajon, A., Zhang, J., Jobling, T., Quinn, M. A., Ostor, A. G., et al. (2002) Presence of active gelatinases in endometrial carcinoma and correlation of matrix metalloproteinase expression with increasing tumor grade and invasion. Cancer, 94, 1466–1475.

Chirco, R., Liu, X. W., Jung, K. K., & Kim, H. R. C. (2006) Novel functions of TIMPs in cell signaling. Cancer and Metastasis Reviews, 25(1), 99–113. doi: 10.1007/s10555-006-7893-x.

Curry, T. E., Jr., & Osteen, K. G. (2003) The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocrine Reviews, 4, 428–465. doi: 10.1210/er.2002-0005.

Amalinei, C., Cianga, C., Balan, R., Cianga, P., Guisca, S., & Caruntu, I.-D. (2011) Immunohistochemical analysis of steroid receptors, proliferation markers, apoptosis related molecules, and gelatinases in non-neoplastic and neoplastic endometrium. Annals of Anatomy, 193(1), 43–55. doi: 10.1016/j.aanat.2010.09.009.

Yu, F., Jiang, Q.P., Zhou, Y., Yang, Zh., Yu, X., Wang, H., et al. (2012) Abnormal expression of matrix metalloproteinase-9 (MMP9) correlates with clinical course in Chinese patients with endometrial cancer. Disease Marker, 32, 321–327. doi: 10.3233/DMA-2011-0886.

Dabbs, D. J. (2010) Diagnostic Immunohistochemistry. New York: Ch. Livingstone.

Tumanskyi, V. O., Yevsieiev, A. V., Kovalenko, I. S., Zubko, M. D. ; Zaporizkyi derzhavnyi medychnyi universytet (patentee) (2015) Patent Ukrainy na korysnu model №99314 Ukraina, MPK (2015) G01N 21/00, G06K 9/00. Sposib fototsyfrovoi morfometrii imunohistokhimichnykh preparative [Ukraine patent for utility model №99314 Ukraine, morphometry immunohistochemical method fototsyfrovoyi drugs МПК (2015) G01N 21/00, G06K 9/00]. Biuleten, 10. [in Ukrainian].

Rasband, W. S. & ImageJ, U. S. National Institutes of Health, Bethesda, Maryland, Retrieved from USA – http://imagej.nih.gov/ij/, 1997–2012.

Jeziorska, M., Nagase, H., Salamonsen, L. A., & Woolley, D. E. (1999) Immunolocalization of the matrix metalloproteinases gelatinase B and stromelysin 1 in human endometrium throughout the menstrual cycle. J Reproduction and Fertility, 107, 43–51. doi: 10.1530/jrf.0.1070043.

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 J Gynecol Oncol, 19(1), 57–67.

Wlaźlak, Е., Surkont, G., Kobos, J., Tyliński, W., Stetkiewicz, T., & Suzin, J. (2006) Expression of metalloproteinases MMP-1 and MMP-9 and tissue inhibitor of metalloproteinases TIMP-1 in cases of endometrial carcinoma and endometrial hyperplasia. Menopause Review, 6, 363–366.

Määtä, M., Soini, Y., Liakka, A., & Autio-Harmainen, H. (2000) Localization of MT1-MMP, TIMP-1, TIMP-2 and TIMP-3 messenger RNA in normal, hyperplastic and neoplastic endometrium. Enhanced expression by endometrial carcinomas is associated with low differentiation. Am J Clinical Pathology, 114, 402–411. doi: http://dx.doi.org/10.1093/ajcp/114.3.402.

How to Cite

1.
Chepets AV. Immunohistochemical characterization of the expression of matrix metalloproteinase - 9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in the invasive endometrioid endometrial carcinoma. Pathologia [Internet]. 2015Dec.18 [cited 2024Nov.4];(3). Available from: http://pat.zsmu.edu.ua/article/view/55613

Issue

Section

Original research