Potapov S. M., Halata D. I., Pliten O. M., Sidorenko R. V., Andreev A. V.

PATHOMORPHOLOGY

Scentific article

Testicular tumors is the most common oncological pathology and the main cause of oncological mortality in young men. Testicular germ cell tumors (TGCT) account more than 90% of all neoplasia with this localization. After seminoma, embryonal carcinoma (EС) is the most common TGCT. In recent years the molecular and biological properties of tumors have been actively studied to estimate the risks of further disease progression. Matrix metalloproteinases (MMP) and intercellular adhesion molecules E-cadherin and β-catenin are considered as markers of unfavorable prognosis of malignant neoplasms. The purpose of study. To determine the state of extracellular matrix (ECM) and cell adhesion in testicular EC. Object and methods. The study was performed on the material of 13 removed testicles affected by EC (including 7 cases when EC was a component of mixed TGCT) as well as medical histories of patients who have been examined and treated at the Kharkiv Regional Clinical Center of Urology and Nephrology named after V.I. Shapoval for the period covering 1998-2017. According to the pathological pTNM classification, all observations of the EC were divided into: tumors of group «1» corresponded to stages T1 N0 S0-2, group «2» – T2 N1-3S0-2, group «4» – T2-3N0-3S0-2 with distant metastasis. For studying of state of ECM and cell adhesion in EC expression of the following immunohistochemical markers were investigated: MMP-1, MMP-3 and MMP-9 with their tissue inhibitor TIMP-1 as well as E-cadherin and β-catenin. For the analysis of digital images was investigated technique that allowed to perform processing of images and receive accurate quantitative data of area (S) and intensity (L) of marker expression. Statistical data processing was performed using the statistical package «STATISTICA 13.3 EN trial version». Results. The study of MMP-1, MMP-3, and MMP-9 in EC revealed an increase of these markers synthesis at tumorous progression. It was found that MMP-1, MMP-3 and especially MMP-9 are involved in the carcinogenesis of EC starting from early stages of tumorous progression. At that significant expression of MMP in the EC point to the tendency of this tumor to aggressive course. S of E-cadherin expression was increasing and S of β-catenin on the contrary was decreasing during transition from the initial to the late stages of tumorous progression of EC. Besides, «heterogeneities» presented by foci of immunonegative and immunopositive cells with cytoplasmic and/or nuclear staining are indicating loss of intercellular adhesion. Conclusion. In EC at transition from the initial to the late stages of tumorous progression a significant increasing of S and L of MMP expression, as well as a complete absence of TIMP-1 expression were detected. At the progression of EC there is a decrease of S of E-cadherin expression up to its complete reduction and, conversely, an increase of S of β-catenin expression in combination with atypical localization of these markers, reflecting the loss of intercellular adhesion. MMP, their inhibitor TIMP-1, as well as E-cadherin and β-catenin may be independent factors of prognosis of the metastasis and progression in patients with EC.

testicular embryonal carcinoma, extracellular matrix, intercellular adhesion, immunohistochemical investigation

1. Burova EA, Bulanov AA, Tryakin AA, Fedyanin MYu, Tyulyandin SA, Matveev VB. Lechenie seminomy yaichka i stadii. Onkourologiya. 2010;3:7- 11. [in Russian].
2. Imyanitov EN. Epidemiologiya i biologiya germinogennykh opukholey. Prakticheskaya onkologiya. 2006;7(1):1-5. [in Russian].
3. Nemtsova MV, Ivkin EV, Tryakin AA, Rudenko VV, Dantsev IS, Tyulyandin SA, et al. Geneticheskiye faktory riska razvitiya sporadicheskikh germinogennykh opukholey yaichka. Urologiya. 2017;1:24-30. [in Russian].
4. Mustafa SA, Mitla V, Banday SZ, Kuchay S. Profile of Testicular Germ Cell Tumors in Kashmir: A Retrospective Analysis. International J. of Scientific Study. 2017;5(4):183-6.
5. Moch H, Humphrey PA, Ulbright TM, Reuter VE, editors. WHO Сlassification of Tumours of the Urinary System and Male Genital Organs (4th edition). Lyon: IARC; 2016. 356 p.
6. Escaff S, Fernández JM, González LO, Suárez A, González-Reyes S, González JM, et al. Study of matrix metalloproteinases and their inhibitors in prostate cancer. Br J Cancer. 2010 Mar 2;102(5):922-9. DOI: 10.1038/sj.bjc.6605569
7. Rogova LN, Shesternina NV, Zamechnik TV, Fastova IA. Matriksnyye metalloproteinazy, ikh rol v fiziologicheskikh i patologicheskikh protsessakh (obzor). Vestnik novykh meditsinskikh tekhnologiy. 2011;18(2):86-9. [in Russian].
8. Kushlinskiy NE, Gershteyn ES. Matriksnyye metalloproteinazy i komponenty sistemy aktivatsii plazminogena v patogeneze i klinicheskom techenii raka tolstoy kishki. Patogenez. 2013;11(3):4-12. [in Russian].
9. Avdoshin VP, Babichenko II, Kotelnikova EV. Prognosticheskoye znacheniye ekspressii immunogistokhimicheskikh markerov Ki-67. MMP-9 i kollagena IV u bolnykh papillyarnym urotelialnym rakom mochevogo puzirya. Onkourologiya. 2011;3:75-9. [in Russian].
10. Ozgüven BY, Karaçetin D, Kabukçuoğlu F, Taşkin T, Yener Ş. Immunohistochemical study of E-cadherin and β-catenin expression in colorectal carcinomas. Pol J Pathol. 2011;62(1):19-24.
11. Shponka IS, Kovtunenko OV, Poslavska OV, Bereznyuk DV, Timchuk SM. Analiz markeriv mizhklitinnoi adgezii u khvorikh na ploskoklitinniy rak orofaringealnoi dilyanki. Bukovinskiy medichniy visnik. 2012;16(1):104-9. [in Ukrainian].
12. Filiz AI, Senol Z, Sucullu I, Kurt Y, Demirbas S, Akin ML. The survival effect of E-cadherin and catenins in colorectal carcinomas. Colorectal Dis. 2010 Dec;12(12):1223-30. DOI: 10.1111/j.1463-1318.2009.01994.x
13. Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008 May 15;68(10):3645-54. DOI: 10.1158/0008-5472.CAN-07-2938
14. Brabletz T, Jung A, Dag S, Reu S, Kirchner T. [beta-Catenin induces invasive growth by activating matrix metalloproteinases in colorectal carcinoma]. Verh Dtsch Ges Pathol. 2000;84:175-81.
15. Brabletz T, Jung A, Reu S, Porzner M, Hlubek F, Kunz-Schughart LA, et al. Variable beta-catenin expression in colorectal cancers indicates tumor progression driven by the tumor environment. Proc Natl Acad Sci USA. 2001 Aug 28;98(18):10356-61.
16. Matsuoka T, Mitomi H, Fukui N, Kanazawa H, Saito T, Hayashi T, et al. Cluster analysis of claudin-1 and -4, E-cadherin, and β-catenin expression in colorectal cancers. J Surg Oncol. 2011 Jun 1;103(7):674-86. DOI: 10.1002/jso.21854
17.  Wang L, Cheng H, Liu Y, Wang L, Yu W, Zhang G, et al. Prognostic value of nuclear β-catenin overexpression at invasive front in colorectal cancer for synchronous liver metastasis. Ann Surg Oncol. 2011 Jun;18(6):1553-9. DOI: 10.1245/s10434-010-1519-9
18. Lobo J, Costa AL, Vilela-Salgueiro B, Rodrigues Â, Guimarães R, Cantante M, et al. Testicular germ cell tumors: revisiting a series in light of the new WHO classification and AJCC staging systems, focusing on challenges for pathologists. Hum Pathol. 2018 Dec;82:113-24. DOI: 10.1016/j. humpath.2018.07.016
19. Potapov SM, Markovskiy VD, Kulishova NE, vynakhidnyky; Kharkivskyi natsionalnyi medychnyi universytet, patentovlasnyk. Sposib kilkisnoi otsinky rivnia svitlosti ta vidnosnoi ploshchi ekspresii markeriv pry imunohistokhimichnomu doslidzhenni tkanyn. Patent Ukrainy №119922. 2019 Serp 27. [in Ukrainian].
20. Kobzar AI. Prikladnaya matematicheskaya statistika. Dlya inzhenerov i nauchnyih rabotnikov [Internet]. Fizmatlit; 2012. 816 s. Dostupno: http://www.studentlibrary.ru/book/ISBN9785922113755.html [in Russiаn].
21. Runyon RP. Nonparametric Statistics: A Contemporary Approach (Addison-Wesley series in statistics). Addison-Wesley Publishing Co; 1977. 218 p.
22. Patel BP, Shah SV, Shukla SN, Shah PM, Patel PS. Clinical significance of MMP-2 and MMP-9 in patients with oral cancer. Head Neck. 2007 Jun;29(6):564-72.
23. Lynch CC, Matrisian LM. Matrix metalloproteinases in tumor-host cell communication. Differentiation. 2002 Dec;70(9-10):561-73.
24. Andreyeva YuYu. Morfologicheskiye i molekulyarno-biologicheskiye faktory prognoza raka mochevogo puzyrya [dissertatsiya]. Moskva: Moskovskiy nauchno-issledovatelskiy onkologicheskiy institut im. P.A. Gertsena Rosmedtekhnologiy; 2009. 64 s. [in Russiаn].
25. Berx G, van Roy F. Involvement of members of the cadherin superfamily in cancer. Cold Spring Harb Perspect Biol. 2009 Dec;1(6):a003129. DOI: 10.1101/cshperspect.a003129
26. Mashukov AA. Molekulyarno-geneticheskiye osobennosti raka zheludka: obzor. Vestnik morskoy meditsiny. 2016;4:161-9. [in Russian].
27. Perevoshchikov AG, Delektorskaya VV, Golovkov DA. Molekuly mezhkletochnoy adgezii kak faktory invazii i metastazirovaniya pri rake tolstoy kishki. Molekulyarnaya meditsina. 2007;1:50-4. [in Russian].
28. Pyo SW, Hashimoto M, Kim YS, Kim CH, Lee SH, Johnson KR, et al. Expression of E-cadherin, P-cadherin and N-cadherin in oral squamous cell carcinoma: correlation with the clinicopathologic features and patient outcome. J Craniomaxillofac Surg. 2007 Jan;35(1):1-9.

«Bulletin of problems biology and medicine» Issue 4 Part 1 (153), 2019 year, 246-254 pages, index UDK 616.61 – 006.6 – 018.1 – 092.18

10.29254/2077-4214-2019-4-1-153-246-254