STATE OF EXTRACELLULAR MATRIX AND CELL ADHESION IN TESTICULAR EMBRYONAL CARCINOMA

Abstract

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 year s 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.

Keywords

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