Expression of cancer-associated genes in prostate tumors.

BACKGROUND:  Prostate cancer is one of the most common male cancers in Western countries and takes the third place in morbidity in Ukraine. It is a highly heterogeneous disease. AIM: To analyze relative expression levels of the TGFB1, IL1B, FOS, EFNA5, TAGLN, PLAU, and EPDR1 genes in malignant and non-malignant prostate tissues. MATERIALS AND METHODS:  Total RNA was isolated from 16 prostate adenomas, 37 prostate adenocarcinomas, and 29 conventionally normal prostate tissues. To analyze relative gene expression levels the quantitative real-time polymerase chain reaction was performed. RESULTS: The significant alterations in the relative expression levels were found in all analyzed sample groups for 4 genes: FOS, EFNA5, IL1B, and TGFB1. We have found that FOS and EFNA5 were more frequently overexpressed in carcinomas with Gleason score ≤ 7, compared with adenomas. On contrary, PLAU expression levels were decreased more frequently in prostate cancers, compared with conventionally normal tissues. Noteworthy, we found positive correlation between IL1B expression level and PSA (for patients with slight PSA increase, no more than 20.0 ng/ml). CONCLUSION: The EFNA5, FOS, IL1B, PLAU, and TGFB1 genes that showed significant expression alterations in prostate tumors, compared with conventionally normal prostate tissue, may play role in prostate cancer development and should be further investigated.

FOXP3 gene promoter methylation in endometrial cancer cells.

AIM: To determine the methylation level of promoter region of the FOXP3 gene promoter depending on the heterogeneity of intracellular localization of its protein product in endometrial cancer (EC) cells and assess its relation to the clinical and morphological features of tumor. MATERIALS AND METHODS: Samples of surgical material of 40 EC patients who have not received any specific treatment before the surgery, were studied. Real time methylation-specific PCR (MSP) as well as morphological and immunohistochemical methods were used in the study. RESULTS: Methylation of promoter region of the FOXP3 gene was determined in all EC cases, but variability of the methylation level in EC cells from 45.0% to 85.0% was observed. With tumor progression and in tumors with deep (≥ 1/2) invasion in myometrium, an increase of the methylation level of the FOXP3 and of cell number with cytoplasmic FOXP3 localization was observed. In EC patients the correlation between of methylation level of the FOXP3 gene and the number of FOXP3(+) tumor cells with cytoplasmic expression (r = 0.41) was determined. CONCLUSION: The methylation level of FOXP3 gene promoter region and intracellular localization of its protein product are associated with tumor differentiation grade and the depth of myometrial invasion.

The study of mismatch repair in endometrial cancer patients with a family history of cancer.

AIM: To assess the expression of mismatch repair (MMR) proteins MSH2 and MLH1 and carry out microsatellite analysis in patients with endometrial cancer (EC) with regard to the family history of cancer. MATERIALS AND METHODS: Morphological and immunohistochemical study was performed on tumor tissue samples of 49 EC patients. Microsatellite instability was determined using PCR with primers which flank microsatellite region BAT-26. RESULTS: A tendency to a decreased expression of both MSH2 and MLH1 markers in a group of EC patients with a family history of cancer as compared with a group without aggregation of cancer in family history was observed (labeling index - LI - was 36.1 ± 8.1% and LI 20.7 ± 9.1% versus LI 48.0 ± 5.8% and 33.8 ± 5.8%, respectively). It was determined that the number of EC patients with tumors deficient by expression of MMR markers was reliably higher in a group of patients with a family history of cancer than in a group of patients without aggregation of cancer in family history (р < 0.05). It was shown that in a group of EC patients with a family history of cancer, MMR-proficient tumors were detected in 38.5% of cases. Microsatellite instability was determined in 10.7% of EC patients including one patient with aggregation of Lynch-associated tumors in family history. CONCLUSION: Family history of cancer of EC patients is associated with malfunctioning of the MMR system as well as may be related to alternative molecular mechanisms.

[BRAF-STATUS OF PAPILLARY THYROID CARCINOMAS AND STRATEGY OF SURGICAL TREATMENT].

Analyzed the presence of BRAF V600E mutation in the focal thyroid gland in the preoperative diagnosis of papillary carcinoma (PC). Molecular genetic testing conducted on puncture aspirates from 26 patients before surgery. The diagnosis was verified according to the morphological investigations. Mutations in BRAF V600E detected only in patients with the thyroid PC. Thus, the definition of BRAF V600E mutation may be a marker in the preoperative diagnosis of thyroid PC. Analyzed the presence of BRAF V600E mutation in the focal thyroid gland in the preoperative diagnosis of papillary carcinoma (PC). Molecular genetic testing conducted on puncture aspirates from 26 patients before surgery. The diagnosis was verified according to the morphological investigations. Mutations in BRAF V600E detected only in patients with the thyroid PC. Thus, the definition of BRAF V600E mutation may be a marker in the preoperative diagnosis of thyroid PC.