Peculiarities of cyclin D1 expression in reproductive and menopausal women with cervical hyperkeratosis.

Morphological diagnosis of cervical intraepithelial neoplastic (CIN) lesions sometimes requires an additional study of molecular markers. Cyclin D1 is a key regulatory protein, which regulates cell cycle progression from G1 to S phase. Disruption of G1/S regulatory mechanisms is basic mechanism of HPV mediated malignant transformation of cervical epithelium. The aim of the research was to study the peculiarities of cyclin D1 protein expression in reproductive and menopausal women with cervical hyperkeratosis. We examined cyclin D1 protein expression in 381 reproductive and 233 menopausal women with cyto-colposcopically detected and histologically proved hyperkeratosis, using immunohistochemical method. Monoclonal ready to use (RTU) antibody against cyclin D1 antigen (Dako) was used. Cyclin D1 positivity in ≤50% of cells considered as low and in ≥50% - as high expression. High expression of cyclin D1 was present in CIN1 of 93,3% reproductive and 66,7% menopausal women, whilst in CINII the high expression was revealed in 53,3% and 43,8% respectively. The weak expression of cyclin D1 was present in only one cases of CINIII, other CINIII cases were all negative. The expression of cyclin D1 protein in cervical intraepithelial neoplastic lesions is not regular, however the overexpression of cyclin D1 is almost always present in CIN1 of reproductive women, in which it might be considered as an additional diagnostic marker.

[The characteristics of proliferation activity in squamous metaplasia and reserve cell hyperplasia of uterine cervix].

The aim of our study was to investigate the characteristics of proliferation activity in squamous metaplasia and reserve cell hyperplasia of uterine cervix. Four groups of patients were selected: 1st group--34 reproductive patients with reserve cell hyperplasia, 2nd group--21 reproductive patients with squamous metaplasia, 3rd group--12 postmenopausal patients with reserve cell hyperplasia, 4th group--29 postmenopausal patients with squamous metaplasia. These groups included the patients with and without infections. Cervical biopsies were studied by immunohistochemistry using anti-Ki-67 monoclonal antibody. Ki-67(+) reserve cells were counted in reserve cell hyperplasia. Ki-67(+) squamous cells were counted in squamous metaplasia. The results showed that in both squamous metaplasia and reserve cell hyperplasia the number of Ki-67(+) cells, i.e. the intensity of proliferation is depended on the co-existence of infection, as well as on the age of the patient. These data are important in the complex treatment of cervical pseudoerosions.

[Morphological changes of cardiovascular system at experimental hypertension, caused by no inhibition in condition of the laser irradiation of low-frequency].

The aim of our study was the investigation of the morphological changes of cardiovascular system, caused by NO inhibition during the laser irradiation of low-frequency. On reception of L NAME and a low-frequency laser irradiation arterial pressure during all experiment remains within the norm. At slight increase of phonic arterial pressure the laser irradiation proved to be less effective, while on a background of high arterial pressure the irradiation does not interfere the further development of hypertension and persistency. Immediately after reception of L NAME and at a low-frequency laser irradiation, the fibrosis and inflammatory changes of myocardium have not been observed; on the background of the slight enhancement of arterial pressure, laser irradiation causes insignificantly expressed fibrosis, inflammatory changes in myocardium; while on the background of increased arterial pressure a laser irradiation doesn't interfere development of fibrosis, myocardium and inflammatory changes in it. Immediately after reception L NAME and at a laser irradiation of low-frequency from the third day, a damage of cardiovascular walls, inflammatory changes, perivascular fibrosis have not been developed, while on the background of increased arterial pressure the irritation doesn't interfere the development of the above mentioned changes. Thus, the irradiation of a low-frequency laser might be recommended to prevent the development of hypertension and to avoid the complications of pre-clinical phase of hypertension. Though, the analogous recommendations are not foreseen for involvement in algorithm of the treatment of hypertension and correction of clinical evidence of the disease.

[The immunohistochemical characteristics of cervical glandular intraepithelial neoplasias].

The aim of our study was to identify immunohistochemical diagnostic criteria for cervical glandular intraepithelial neoplasias (CGIN). We examined 136 women with cytological diagnosis of atypical endocervical cells. These patients were divided into three groups based on a grade of the lesion: 35 patients with CGIN1 (group I), 72 patients with CGIN2 (group II), 28 patients with CGIN3 (group III). Endocervical curettages were examined by hematoxylin-eosin and immunohistochemistry using monoclonal antibodies against Ki-67, EpAg, MNF116, CEA, EMA. We used histological algorithm created by us. The comparative analysis of immunohistochemical results showed that expression of Ki-67 is seen in CGIN 2 and significantly increased in CGIN3 (p<0,05) which indicates increased proliferative activity of glandular cells in relation to increased grade of lesion. The differences in the expression of MNF116 and EMA are not statistically significant (p>0,05) which indicates that the expression of these epithelium specific markers does not change according to the grade of atypia and carcinogenesis (they can be used for determination of tumor phenotype). The expression of CEA and EpAg is strongly increased in CGIN2 and CGIN3 (p<0,05) indicating their potential role in carcinogenesis. The results suggest that evaluation of a grade of cervical glandular intraepithelial neoplasia should be based on histological and immunohistochemical studies. The morphometric algorithm should include the following criteria: type of lining epithelium (cubical, columnar), nuclear cytoplasmic index (<1, >1, =1), stratification, hyper- and hypochromasia, size and amount of nucleoli, and stromal-parenchymal ratio. The immunohistochemical study should include the expression of proliferation marker (Ki-67), carcinoembryonic antigen (CEA)and Epithelial Antigen (EpAg). We recommend the classification of CGIN into two types: low grade cervical glandular intraepithelial neoplasia (CGIN 1) and high grade cervical glandular intraepithelial neoplasia including CGIN 2 and CGIN 3.

[Determination of cytomorphological criteria for differential diagnostics of variable stages of endocervical glandular cells atypia].

The aim of the investigation was to determine the criteria of differential diagnostics of different stages atypia of endocervical cells in women of different age groups. For ECCIN3, out of 12 diagnostic criteria, the most important and statistically significant were the following five: a) high N/C index > 5,54; b) number of mitoses > 10,3; c) number of produced rosettes >3,9; d) rough redistribution of chromatin >4,64; e) hyperchromatosis >1,87. In case of ECCIN3 the majority of patients (82,75%) had infection of the cervix. In 13,79% of patients HPV infection has been documented. Hemorrhagic discharge was a very characteristic symptom (57,12%) of ECCN3.