[Expression of microRNA let-7a, miR-155, and miR-205 in tumor and tumor-adjacent histologically normal tissue in patients with non-small cell lung cancer]. / Ekspressiya mikroRNK let-7a, miR-155, miR-205 v opukholevoi i smezhnoi morfologicheski normal'noi tkani u patsientov nemelkokletochnym rakom legkogo.

UNLABELLED: Non-small cell lung cancer (NSCLC) is a main group of lung malignancies. Epigenetic changes are as important as genome structural changes in carcinogenesis. MicroRNA (miRNA) is a class of non-coding single-stranded RNAs that play an important role in the regulation of matrix RNA (mRNA) translation and degradation. MicroRNA expression changes occur in many cancers. According to the field cancerization theory, tumor-adjacent histologically normal tissue takes part in tumor progression by triggering cell transformation. The important clinical implication is that the fields may serve as the basis for a recurrence after surgery. Thus, the aim of our study was to determine the expression levels of miRNAs let-7a, miR-155, and miR-205 in tumor and tumor-adjacent apparently normal tissues to evaluate these changes as potential prognostic markers in NSCLC patients. METHODS: The expression of miRNAs let-7a, miR-155, and miR-205 in tumor and tumor-adjacent apparently normal tissues at 2 and 5 cm was determined by real-time PCR with subsequent quantification using a 2-ΔΔСt method. The findings were then analyzed to reveal possible associations with clinical and morphological parameters, such as age, cancer stage, and tumor grade. RESULTS: The expression of miRNA let-7a was found to be significantly lower in tumor than that in tumor-adjacent apparently normal tissue at 2 and 5 cm. In groups of patients older than 63 years with Stage III-IV NSCLC, the expressions of microRNA let-7a and miR-155 in tumor tissue were substantially lower than that in the adjacent normal tissue. Beyond that point, patients with high-grade tumors had also a significantly lower expression of miRNA let-7a in relatively adjacent apparently normal tissue. CONCLUSION: The findings suggest that miRNA let-7a and miR-155 may be used as poor prognostic markers for patients with NSCLC.

[Intravascular leiomyomatosis].

Intravenous leiomyomatosis is a rare disease from a group of tumors with the indefinite grading potential. The paper describes two cases of intravenous leiomyomatosis with its detailed morphological pattern, molecular genetic findings, and a brief literature review. Losses of heterozygosity of microsatellite repeats thatwere located on chromosome 10 in 10q22.1 and common in uterine leiomyosarcomas were found in both cases. Investigations of the morphological and biological characteristics of leimyomatosis are important to clarify the key molecular mechanisms underlying the development of this nosological entity and to determine etiopathogenetic relationships between intravenous leiomyomatosis and other uterine smooth muscle neoplasms.

[Diagnostic value of estimation of ERG expression in prostate adenocarcinoma and high-grade prostatic intraepithelial neoplasia].

OBJECTIVE: to estimate the diagnostic and prognostic value of analyzing the abnormal overexpression of the chimeric protein ERG, encoded by the chimeric gene TMPRSS2/ERG, in prostatic neoplasias. MATERIAL AND METHODS: A total of 100 prostate adenocarcinoma samples were examined. The presence of tumor and high-grade prostatic intraepithelial neoplasia (hPIN) was verified by immunohistochemical tests using anti-P504S and anti-34ßE12 antibodies in serial sections; RT-PCR was employed to analyze the chimeric transcript TMPRSS2/ERG in 30 prostate adenocarcinoma samples. RESULTS: ERG expression was noted in 46% of the adenocarcinomas and in 21% of hPIN. Eight (8%) patients were observed to have heterogeneous ERG expression: the marked reaction in some tumor portions was concurrent with its complete absence in others. Furthermore, there was ERG expression in all cases of intraductal (noninvasive) carcinoma (the foci of intraductal carcinoma were assessed as atypical cribriform lesions by light microscopy). The prognostic value of ERG expression could not be determined at the current stage of the investigation. CONCLUSION: The relatively low rate of ERG-positive hPIN counts in favor of the limited role of this marker in the differential diagnosis of hPIN. ERG in combination with P504S and 34ßE12 is an informative marker for the differential diagnosis of hPIN with intraductal carcinoma.

[Allelic imbalance in patients with non-small cell lung cancer].

Non-small cell lung cancer (NSCLC) comprises 80% of all lung cancers and is characterized by multiple genetic alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI). The aim of the study was to analyze of molecular-genetic alterations in tumor and tissue surrounding the tumor to determine genetic features of different histological types of NSCLC and its possible associations with clinicopathological parameters of patients. A microsatellite analysis of chromosomal regions 12p23.3, 2q35, 3p14.2, 3p22.2, 3p26.3, 9p22.1, 17p13.3 was performed. The frequency of genetic alterations in NSCLC was 50% in average. LOH/MSI in the tumor surrounding tissue at 2 and 5 cm. from tumor was not detected. There were statistically significant associations between LOH and/or MSI and the tumor stage, its histological type and smoking status. The found genetic alterations can be used as molecular markers of squamous cell lung cancer in difficult diagnostic cases and appraised as prognostic markers.

[Benign metastatic leiomyoma of the corpus uteri].

Benign metastasizing leiomyoma (ICD.0 8898/1) is a rare phenomenon characterized by multiple benign smooth muscle tumors (metastases) in the organs and tissues of patients with uterine leiomyoma without evidence for another tumor process. This tumor should be differentiated from leiomyosarcoma, at the same time account must be taken of the fact that its morphological criteria are not always effective. Molecular genetic testing is a more accurate method that allows valid differentiation of leiomyoma from leiomyosarcoma. Genetic testing is used to estimate losses of heterozygosity and microsatellite instability, which are characteristic of leiomyosarcoma only. The paper describes a clinical case of benign metastasizing leiomyoma in a 54-year-old patient with uterine myoma and pelvic lymph node metastasis. Molecular genetic testing was carried out using the samples obtained from primary uterine leiomyoma, morphologically altered ovarian tissue, and lymph node metastasis to determine the common origin of tumors in the uterus and lymph node and to reveal the benign or malignant nature of these neoplasms. Despite the fact that the term "benign metastasizing leiomyoma" is widely accepted in the world literature, neither these tumors nor metastases have morphological or genetic signs of malignancy so we consider the term "systemic leiomyomatosis" to better reflect the essence of this process.

[The loss of heterozygosity and microsatellite instability analysis in differential diagnostics of leiomyosarcoma and proliferative leiomyoma of the uterus].

Uterine leiomyosarcoma (ULMS) is rare and highly malignant smooth muscle tumor. The different diagnosis between uterine leiomyoma with high proliferative index (ULM) and ULMS is one of the basic problems in the pathology for nowadays. We had investigated the loss of heterozygosity (LOH) and microsatellite instability (MI) to find out a genetic differences between ULM and ULMS. The inicrosatellite analysis was evaluated by PCR using 6 polymorphic markers for chromosomal regions 10q22.1 (D10S1146, D010S218), 10q26.13 (D10S1213), 10p13 (D10S24), 9p21.3 (D9S942), 3p14.3 (D3S1295) in 20 patients with ULMS. 38 patients with ULM were suggested as control group. Our results have demonstrated high frequency allelic imbalance in ULMS samples (average frequency 40%). The comparative analysis between 2 studied groups of patients has been shown higher frequencies of genetic changes for ULMS. Specificity and sensitivity of the LOH and/or MI markers scores 92 and 95% accordingly.