HISTOPATHOLOGICAL, PROLIFERATIVE, APOPTOTIC AND HORMONAL CHARACTERISTICS OF VARIOUS TYPES OF LEIOMYOMAS.

Uterine leiomyomas decrease the quality of life by causing significant morbidity among women of reproductive age. Histologically various types of leiomyoma's can be differentiated. We have analysed the histopathological, proliferation, apoptotic and hormonal profile in different types of leiomyomas. Study included altogether 140 cases distributed into following groups: group I - normal myometrium (20 cases), group II-classic leiomyoma (69 cases), group III-cellular leiomyoma (15 cases), group IV - bizarre cell/atypical leiomyoma (22 cases), group V - smooth muscle tumors of uncertain malignancy potential (STUMP) (8 cases) and group VI - leiomyosarcoma (6 cases). Together with classic histopathological features such as nuclear atypia, cellularity, presence of mitoses, vasculature and necrosis, immunohistochemical phenotype using antibodies against Ki67, Cas3, ER and PR were analysed. The results of our study showed that leiomyomas are characterised with variable histopathological and immunohistochemical phenotype. Especially, two entities, bizzare/atypical leiomyoma and STUMP, which can be divided into two subgroups according to the presence of the degree of atypia and the expression of proliferation, apoptosis and hormonal markers, which might be the explanation of their different prognosis. Presented histopathological and immunohistochemical features should be considered in the diagnosis of myometrial smooth muscle tumors.

PHENOTYPIC CHARACTERISTICS OF RELAPSED LEIOMYOMA AND SMOOTH MUSCLE TUMORS OF UNCERTAIN MALIGNANCY POTENTIAL IN REPRODUCTIVE WOMEN.

Uterine leiomyoma represents the most common pelvic tumor in females, including numerous histological subtypes, from which smooth muscle tumors of uncertain malignancy potential (STUMP) represents the diagnostic challenge. On the other hand, the study of the relapse risk markers after laparoscopic myomectomy is of high interest. We investigated the molecular phenotype of different types of leiomyoma after hysterectomy or laparoscopic surgery in reproductive and menopausal women. Standard immunohistochemistry was used to detect proliferation markers Ki67 and cyclin D1, apoptotic markers Bcl2 and Cas3, and ER and PR. The results of our study indicated that ER expression is significantly higher in relapsed leiomyoma, compared to control group. In addition, relapsed leiomyomas are characterised with high proliferation and apoptotic index. With regard to STUMP despite histological homogeneity, this entity is characterised with the presence of three distinct molecular subtypes, based on proliferation and apoptotic marker expression, which should be used as diagnostic aid in these tumors.

DISTRIBUTION OF INTRAEPITHELIAL LYMPHOCYTES AND MACROPHAGES IN CERVICAL MICROENVIRONMENT DURING THE PROGRESSION OF CERVICAL INTRAEPITHELIAL NEOPLASIA.

Microenvironment plays central role in the development of cervical precancerous and cancerous lesions. Cervical intraepithelial neoplasia (CIN) represents a group of precancerous lesions, divided into three degrees. We investigated the distribution of intraepithelial lymphocytes and macrophages in different grades of CIN. We analysed lymphocyte marker CD103, macrophage marker CD68 and proliferation marker Ki67 using standard immunohistochemistry. In addition, we investigated the distribution of lymphocytes using standard haematoxylin and eosin method. The results of our study indicated thatgrade I CIN which subsequently progressed into grade II CIN was characterised with low lymphocytic infiltration, low lympho-epithelial index and low lymphocyte proliferation index. Similar results were seen in cases of CINII which were later progressed into CINIII or in carcinoma. Therefore, we would like to recommend the analysis of microenvironment alterations in CIN lesions, in order to assess their progression potential.

TLR9 EXPRESSION, LANGERHANS CELL DENSITY AND LYMPHOCYTIC INFILTRATION IN PROGRESSING CERVICAL INTRAEPITHELIAL NEOPLASIA.

Toll like receptors (TLRs), NK cells, Langerhans cells and T cells play an important role in the protection of host organism from human papilloma virus (HPV) infection. The aim of our study was to analyse TLR9 expression, Langerhans cell density and NK cell and Lymphocytic infiltration in the progression of cervical intraepithelial neoplasia (CIN). By using standard immunohistochemistry, we have investigated TLR9, CD1a Langerhans cell marker, CD56 NK cell marker, CD3 general T cell marker, CD4 T helper cell marker and CD8 cytotoxic T cell marker. We have introduced NK cell epithelial index and Langerhans cell epithelial index. In addition, we have introduced proliferation apoptotic index of lymphocytes using Ki67 and BCL2 markers. The results of our study showed that TLR9 expression, T cell infiltration and NK epithelial index is significantly increased during the progression of CIN disease. Whilst Langerhans cell epithelial index is significantly decreased. Proliferation apoptotic index of lymphocytes is also significantly decreased during the progression of CIN. Based on our study results we recommend the assessment of TLR9 and proliferation apoptotic index as an additional markers for defining CIN progression potential.

Prevention and treatment strategy in pregnant women with group B streptococcal infection.

Group B streptococcus (GBS; Streptococcus agalactiae) are encapsulated gram-positive cocci belonging to Lancefield group B, that frequently colonizes the human genital and gastrointestinal tracts. It is an important cause of illness in three categories of population: infants, pregnant women, and adults with underlying medical conditions. In pregnant women and postpartum women, GBS is a frequent cause of asymptomatic bacteriuria, urinary tract infection, upper genital tract infection (i.e. intraamniotic infection or chorioamnionitis), postpartum endometritis (8%), pneumonia (2%), puerperal sepsis (2%), and bacteremia without a focal site (31%). It also can cause focal infections such as pneumonia, meningitis, and endocarditis, albeit rarely. Invasive maternal infection with GBS is associated with pregnancy loss and preterm delivery. Prior to the widespread use of maternal intrapartum chemoprophylaxis, maternal colonization with GBS conferred an increased risk of chorioamnionitis, and early postpartum infection. The serotype distribution of invasive GBS infection in pregnant women is similar to that of early-onset neonatal disease. The most common GBS serotypes causing invasive disease in adults and neonates are Ia, Ib, III, and V. Vaccination of adolescent women is considered an ideal solution. However, recent reports (April 2015) have shown that serotype IV GBS is emerging in pregnant carriers and causing infections in neonates and adults. This emergence is of concern because GBS conjugate vaccines that are being developed to prevent invasive disease may protect only against serotypes Ia, Ib, II, III, and V, or combinations thereof. Though research for the development of such a vaccine is underway, a good candidate vaccine has yet to surface.

[A, M and G immunoglobulins during premature pregnancy].

Immunological process develops as a result of the failure of mechanisms providing the state of conditional tolerance of maternal immune system in regard to antigens of feto-placental complex. Immune response is mainly directed towards maintenance of internal homeostasis of maternal organism in critical conditions, and as a result interruption of pregnancy takes occurs. Development of pregnancy leads to more expressed decrease of T-cellular indices, as well as of humoral immunity. The state of immunodeficiency increases vulnerability of woman organism to damaging agents, what, in its turn, promotes development of immunopathological process.

[Blood cells at premature and physiological pregnancies].

Erythrocytes are integrated into the net of regulating mechanisms, having a significant importance in the course of pregnancy and together with nervous, endocrine and immune systems play an important task -- maintains functional integrity of the organism in changeable environment. Preparation for labor activities in women with physiological pregnancy begins with absolute normalization of rheological indices in order to maintain the homeostasis in stable state. As to premature pregnancy, here preparation of the organism for labor activities takes place without normalization of rheological indices, while stability of the homeostasis is supported by means of re-distribution of erythrocytes, increase of adhesion of erythrocytes with gigantic forms of thrombocytes, increase of amount of erythrocytes without central unstained areas, increase of HEB penetration, increase of adsorption, etc.