The thesis is devoted to the study of the epidemiological, clinical-morphological and immunohistochemical features of testicular germ cell tumors, taking into consideration the histological type and stage of the tumor progression, which makes it possible to improve the morphological diagnosis and staging, as well as to predict the course of the disease and theoretically substantiate the way of a personalised therapy for a certain patient.
It was found that the degree of tumor lesion was greater in the presence of lymphogenous metastases, than in cases when the lymphogenous metastases were absent. Yolk-sac tumor, post-pubertal type, the embryonal carcinoma and mixed testicular germ cell tumors are the most aggressive, taking into consideration the lymphogenous metastasis, even with a low degree of tumor lesion of the testis; while such tumors as seminoma and teratoma, post-pubertal type, metastasize lymphogenically least often, even with a significant degree of the tumoral damage of the testicle.
Immunohistochemical diagnostics revealed that, in general, testicular germ cell tumors are characterized by low proliferative activity, which, however, increases with the transition from the initial to later stages of tumor progression and depends on the histological type of the tumor: the greatest proliferative activity was noted in yolk-sac tumor, post-pubertal type, the smallest – in post-pubertal teratoma, while the embryonal carcinoma and seminoma take the intermediate position. Testicular germ cell tumors are characterized by a low level of apoptosis, which depends on the histological type of the tumor and the stage of the tumor progression. The greatest apoptotic activity is observed in seminoma; as for yolk-sac tumor, post-pubertal type and post-pubertal teratoma, the apoptosis level approximates zero level of activity.
It was established that the level of expression of MMP-1,-3,-9 depends on the stage of tumor progression and the histological type of testicular germ cell tumors: the highest expression of MMP data is observed in embryonal carcinoma and post-pubertal yolk-sac tumor. The lowest is registered in post-pubertal teratoma and seminoma. Thus, the increase of S and L of MMP-1, MMP-3 and MMP-9 expression can be regarded as a prognostically unfavorable characteristic of the testicular germ cell tumors course.
It was found that in seminoma, embryonal carcinoma, post-pubertal yolk-sac tumor and post-pubertal teratoma, with the progression of the tumor stage, S of E-cadherin expression decreases and β-catenin increases (except for post-pubertal teratoma, in which S of β-catenin decreases), and the membrane and membrane-cytoplasmic location of E-cadherin and β-catenin change to the cytoplasmic, nuclear or nuclear-cytoplasmic synchronically. This proves the significant role of changes in the expression of these markers in gaining of the invasive and metastatic potential of testicular germ cell tumors. In the initial stages of tumor progression, S of E-cadherin expression in seminoma and embryonal carcinoma exceeds the one in post-pubertal yolk-sac tumor. S of β-catenin expression in post-pubertal yolk-sac tumor is the highest of all the studied histological types of testicular germ cell tumors; though it is higher in embryonal carcinoma than in seminoma. In the later stages of the tumor progression S of E-cadherin expression is the highest in seminoma; as for the embryonal carcinoma and post-pubertal yolk-sac tumor, S of β-catenin expression is higher in them if to be compared with seminoma and post-pubertal teratoma.
The studies revealed that in seminoma, embryonal carcinoma, post-pubertal yolk-sac tumor and post-pubertal teratoma, when the stage of the tumor progresses, S of CD31 expression increases, as well as the vascular density index (except for post-pubertal teratoma). At the initial stages of the tumor progression the vascular density index in post-pubertal yolk-sac tumor is higher than the index in seminoma and post-pubertal teratoma. The vascular density index is distributed as follows: the first place belongs to post-pubertal yolk-sac tumor, the second – to the embryonal carcinoma, the third – to seminoma, and the fourth – to post-pubertal teratoma. In addition to the angio- and vasculogenesis that are common for the testicular germ cell tumors, vasculogenic mimicry was registered in all the histological types of such tumors.
For the first time, a mathematical model was proposed, which makes it possible to determine the histological type and stage of tumor progression in testicular germ cell tumors on the basis of their molecular-biological properties investigation. The optimal panel of immunohistochemical markers which denote the malignant potential of testicular germ cell tumors, and which provide a theoretical basis for a personalized (targeted) treatment of testicular germ cell tumors was proposed.
