EPIGENETIC CHANGES - HISTONE 3 PHOSPHORYLATION - EPITHELIAL OVARIAN TUMORS.

Histone modifications represent one of the types of epigenetic changes. Histones, undergo different types of epigenetic modifications, including the phosphorylation of serine residues. pHH3 antibodies specifically detect histon-3 protein, when phosphorylated at 10th and 28th serine residues. Traditionally pHH3 antibodies are used as proliferation marker, as it detects cells in late G2 and M phase. We studied the distribution of phosphor-histon-3 in epithelial tumors of the ovary and its relationship with ER, PR, Ki67, p53 and BCL2. Altogether, we investigated postoperative material from 160 patients. Standard immunohistochemistry was used to detect, phosphohistone-H3 (pHH3), ER, PR, Ki67, p53 and BCL2. The results of our study showed that phosphohistone-H3 expression is negatively associated with the expression of ER and PR expression, as well as with BCL2 expression, on the other hand it positively correlates with Ki67 and mutant p53 (p<0.05). In addition, the expression of phosphohistone-H3 is detected in Ki67 negative cases and its expression is increased along with the increase of malignancy grade. Our study results indicate that PHH3 might be used as an additional marker for the assessment of proliferation and malignancy potential of epithelial tumors of the ovary.

MORPHOPHENOTYPIC CHARACTERISTICS OF OVARIAN SEROUS BORDERLINE TUMORS.

Borderline ovarian tumors (BOTs) represent particular challenge for diagnosis and clinical management as they are characterized with the features of both benign cystadenomas and malignant carcinomas. The aim of our study was to investigate histomorphological and immunohistochemical characteristics of ovarian serous-papillary borderline tumors, compared to serous cystadenomas and low- and high-grade serous carcinomas. Altogether, 80 formalin fixed and paraffin embedded tissue specimens, distributed in four groups, including serous cystadenoma (group I), serous BOTs (group II), Low (group III) and high (group IV) grade serous carcinomas, were investigated by standard immunohistochemistry, using antibodies against CK7 CK20, WT1, Vimentin, CDX2, CEA, ER, cyclin D1, BCL2, E-cadherin, calretinin, СA125, Ki67, P53. Study results showed, that ovarian serous BOTs are characterized with slightly increase proliferative potential compared to benign cystadenomas, whilst apoptotic potential is retained with the difference from malignant serous carcinomas. p53 mutation is not present, as well as the expression of Vimentin. Overall, ovarian serous BOTs are characterized with highly variable immunohistochemical phenotype and the use of multiple immunohistochemical markers are recommended for the differential diagnosis from low grade serous carcinomas and benign cystadenomas.

BRAF ANTIBODY EXPRESSION IN DIFFERENT TYPES OF THYROID NODULAR LESIONS.

Major problems haunt the physicians who need to delineate the best management strategy for their patients with thyroid nodule is the identification of the most aggressive cases, especially among papillary thyroid cancers, which would benefit from more aggressive therapy and follow up. Beyond its strong correlation with PTC, the BRAF mutation is well described to associate with poor prognosis. The aim of our study was to identify BRAF antibody expression in different hystotypes of the thyroid nodules and assessment of it expression according to the tumor aggressiveness. Immunohistochemical staining was performed in 54 of surgically resected thyroid nodules, including malignant and benign cases, grouped according to the tumor aggressiveness. We have used selected thyroid specific markers: BRAF antibody, CD-56, CK-19, HBME-1 and KI-67. Adenomatous hyperplasia's and follicular lesions doesn't reveal positivity to the expression of BRAF antibody. Encapsulated papillary carcinomas included in our work revealed negative or very poor positivity of BRAF antibody. This fact strengthen the hypothesis that encapsulated papillary carcinomas have an indolent behavior and is genetically distinct from infiltrative tumors. We revealed 55,5% positivity of BRAF antibody in the cases of papillary microcarcinomas, this fact creates a need for more cautious approach to this type of tumors. The degree of BRAF antibody expression increased with a rising of tumor aggressiveness in our histopathologic groups (P<0,005). All cases of papillary carcinoma with multinodular involvement and extrathyroid extension revealed moderate or strong positivity of BRAF antibody expression.

ACCURATE DIAGNOSIS OF THYROID NODULES: A REVIEW OF DIAGNOSTIC DILEMMAS ON THYROID FINE-NEEDLE ASPIRATION BIOPSIES.

FNA biopsy is well known method for the first step evaluation of thyroid nodules, it is the "gold standard" for diagnosis and surgical approach of nodular goiter. Despite the high sensitivity and specificity of the method there are grey zone in the diagnosis of thyroid nodules, mainly due to the heterogeneous group of Bethesda category AUS/FLUS. There are also some difficulties in diagnosis of PTC, especially FVPTC, even on histologic sections. The limited studies exist that specifically address details of cytologic features associated with cytohistologic discrepancy. Cell-block is very helpful in the diagnosis of papillary thyroid carcinoma and the carcinoma of undefined category; as the papillary configuration and nuclear features were more obvious, also immunocytochemical markers are applicable for ancillary studies. The BRAF mutation detection, which is associated with papillary microcarcinomas and cancer, can be yield for preoperative diagnosis, as well as for prognostic marker and as therapeutic target for farther management.

DISTRIBUTION OF THYROID PATHOLOGIES IN DIFFERENT AGE GROUPS IN GEORGIA.

We aimed to analyze the diagnostic criteria proposed by the Bethesda System for reporting thyroid Fine needle aspiration biopsy (FNAB) results. FNABs of 600 patients were performed during 1-year period (2013-2014) in Georgian hospitals (Tbilisi Cancer Center, New Hospitals, National Screening Center). Based on our clinical, ultrasound, FNAB and histology results we define how each diagnostic category of the Bethesda System is distributed among age and sex groups of the cases included in this work. The patient age range was from 20- to 80 years and grouped them in four age groups: I group 20-35 years (n=87), II group 36-50 (n=243), III group 51-65 (n=206) and IV group 66-80(n=64). Histologic correlation was made, defined rate of malignancy. Each diagnostic category conveys specific risk of malignancy, which offers guidance for patient management. Our study showed that the probability of benign nodules is high in our cases, encountered 63,3%. Benign nodules are most commonly found in the group II and III, which are middle age groups. Bethesda class 3 or AUS/FLUS category, which is the most heterogeneous class, carries the rate of malignancy 20,4% and most commonly encountered in group II and III. According to our study particularly noteworthy and interesting was the first age group (20-35 years) because most of the diagnosis of Bethesda class 6 or malignant category was encountered in this age group. Based on our data, it should be noted that there are very high probability of cancer in young age group and it carries high risk of malignancy.