[Correlation of metastasis-free survival in patients with breast cancer and changes in the direction of expression of multidrug resistance genes during neoadjuvant chemotherapy].

Previously, we showed the association of neoadjuvant chemotherapy (NAC) response with changing the expression vector (increase or decrease) of multidrug resistance genes (MDR) in breast tumors during chemotherapy. The aim of the present study was to evaluate the relation between changes in the expression vector of MDR genes and distant metastasis-free survival. Patients (n = 120) with breast cancer (T1-4N0-3M0) treated by 2-4 cycles of NAC (CAX, FAC, and taxane regimes) and 4 cycles of adjuvant chemotherapy (FAC) were included. TaqMan-based quantitative reverse transcriptase PCR (qRT-PCR) was used to estimate the expression of the following MDR genes: ABCB1, ABCC1, ABCC2, ABCC5, ABCG1, ABCG2, GSTP1, and MVP--in biopsies before NAC and in tumor samples after chemotherapy. Comparing the corresponding expression levels allowed us to identify the vector of expression change during NAC. The results showed that 5-year distant metastasis-free survival was 73-78% in patients with a decrease in ABCB1, ABCC2, and ABCG1 expression. The up-regulation of these genes during NAC was related to a significant decrease (up to 50-55%) in metastasis-free survival (Kaplan-Meier analysis: log-rank p value = 0.006-0.03). The association of changing the expression vector of MDR genes with metastasis-free survival did not depend on tumor size, lymph node involvement, histological form, receptor status, molecular subtype, and others clinicopathological parameters of breast cancer. The obtained data suggest that changing the expression vector of MDR genes in breast tumors during NAC may be used as a new potential prognostic marker of breast cancer. An increase in tumor expression of ABCB1, ABCC2, and ABCG1 during chemotherapy is a factor of poor prognosis, whereas down-regulation of these genes--a favorable prognostic marker.

[Dynamics of methylation changes within functional groups of genes during breast cancer progression].

For the first time in a comparative perspective the epigenetic status of the benign proliferative processes, breast cancer, and metastases to regional lymph nodes was studied using DNA methylation microarray "GoldenGate Cancer Panel I" ("Illumina", USA). The functional groups of differentially methylated genes were identified in each set of samples. The genes that regulate cell proliferation and mobility were methylated in samples with benign proliferative processes. An aberrant methylation of the genes responsible for cell differentiation and proliferation, as well as protein phosphorylation and cell mobility was observed in the samples with malignant phenotype. Differential methylation of the genes that regulate cell adhesion, the formation of anatomical structures, angiogenesis, immune response, signal transduction, and protein phosphorylation was found in the samples with metastases to regional lymph nodes in comparison with the morphologically unaltered breast epithelium. The tissues from the benign proliferative processes and metastases to regional lymph nodes were generally characterized by a relatively lower level of epigenetic variability in comparison with the tissues of the primary tumor.

[Different types of 199Tl chloride scintigraphic visualization of malignant tumors of the locomotor apparatus].

BACKGROUND: 201Tl chloride scintigraphy allows malignant tumors of the locomotor apparatus to be diagnosed. The capacities of scintigraphy with 199Tl chloride, a 201Tl chloride analog, in addition to routine visualization of malignant tumors of the locomotor apparatus, have revealed its untypical variants. OBJECTIVE: to study the specific features of 199Tl chloride scintigraphic visualization of malignant tumor processes in the locomotor apparatus. SUBJECTS AND METHODS: 199Tl chloride scintigraphy was performed in 85 patients having 107 foci of involvement presented with malignant (n = 57) and benign (n = 50) tumor processes. RESULTS: Malignant tumors were scintigraphically visualized in 98.1% of cases. Three types of their visualization were identified and studied; these included positive (82.4%) and rare: negative (7.8%), and mixed (9.8%) types associated with the specific features of the histological structure, metabolism, and blood supply of neoplasms and with the pharmacodynamic features of 199Tl chloride. The negative and mixed types, unlike metastatic neoplasms, were highly specific to primary or recurrent malignant tumors. CONCLUSION: Consideration of the negative and mixed types of scintigraphic visualization in addition to routine positive one permitted the sensitivity of diagnosis of malignant locomotor tumors to be increased from 90.4 to 98.1%, without reducing the specificity of 199Tl chloride scintigraphy.

[Proteasome activity in tumors of female reproductive system].

Proteasomes (multiproteinase protein complexes) are known to play an important role in cancer pathogenesis, however, few information about their activity in human tumor tissues is available so far. We studied chymotrypsin-like activity of proteasomes in tissues of breast cancer (BC) and endometrial cancer (EC). The chymotrypsin-like total proteasome activity and the 20S and 26S proteasome activity in malignant tissues were shown to be significantly higher in malignant tumors than in normal tissues. No increase in proteasome activity was registered with larger tumor size in both BC and EC, whereas proteasome activity was changed with respect to the extent of tumor involvement. In breast cancer tissues, significant reductions in the total and the 26S proteaome activities were observed in tumors with regional lymph node metastases as compared to tumors without metastases. In endometrial cancer tissues, the total proteasome activity and the 20S and 26S proteasome activities were increased as the depth of myometrial invasion. The data obtained indicate that the proteasome acyivity is significantly changed in the process of cancerogenesis and further study is needed to develop new additional prognostic criteria and effective anti-tumor agents in molecular-directed therapy.

[Epigenetic aspects of early lymphogenic metastasis in breast cancer].

Metastasizing is one of the key stages in tumor development. Understanding this process is necessary for effective diagnosis, therapy and prediction of clinical outcome. Some recent data suggest the possibility of metastatic phenotype cells appearance at the early stages of tumor evolution in contravention with generally accepted hypothesis of linear metastatic process development. In this study we have performed a comparative analysis of the array-based DNA methylation profile in biopsy samples of patients with benign breast disorders, breast cancer and lymphogenous metastases. In some cases the biopsy samples dated back to different stages of the same tumor. For the analysis the GoldenGate Methylation Cancer Panel I was used. The DNA methylation level in 1,505 CpG-sites was similar in samples from patients with benign breast disorders and lymphogenous metastases. Our data support the hypothesis of the early appearance of cell clones responsible for the tumor limphogenous dissemination. Epigenetic component apparently plays an important role in this process.

[Enzymes of estrogen metabolism in breast cancer and their correlation with outcome].

The biopsy samples of 85 patients with breast cancer (BC) stage T1-3N0-3M0 were studied for estrogen metabolism enzymes (aromatase, 2,4-estrogene hydroxylase and gluthathion transferase) activity. This data was analyzed in relation to disease outcome. Aromatase activity in cancer tissue less than 20 fmol/ mg protein/h and 2,4-estrogene hydroxylase activity more than 230 pmol/mg protein/h proved to be the independent and significant predictors associated with worse relapse-free survival. The activity of gluthathiontransferase in tumor tissue less than 40 mkmol/mg protein/h is associated with worse metastatic-free survival. The activities of estrogen metabolism enzymes may be used as additional prognostic markers for breast cancer outcome.

[Specific features of mammographic visualization of "small" breast tumors developing on the background of fibrocystic disease].

All complications diagnosed at early stages of breast cancer were associated with small tumors, especially with those arising in the aftermath of fibrocystic disease. Hence, our task was to study the XR-semiotics of lesions of less than 15 mm in diameter and of the same origin. 100 mammograms of breast cancer patients with benign disease of the breast were studied. The presence of moderate-to-severe fibrocystic disease significantly affected the visualization of lesions of less than 10 mm in diameter. Since the XR-semiotics of small tumors failed to reveal malignancy features, all lesions visualized by mammography required additional diagnostic procedures using ultrasound and invasive radiology.

[Occult multicentric breast cancer].

The study included 92 patients with invasive ductal breast cancer (T2-4N0-2M0-1). In 38 cases, tumor growth was unicentric while histologically identifiable ones as multicentric in 44. Multicentricity mostly occurred in cases of macroscopically-identifiable nodes located in the central segments of the breast. Clinically-identifiable nodes of multicentric tumor growth measured more than 3 cm. Multicentric tumors were mostly grade III, featured lower expression of sex hormone receptors and positive Her2 status.

[Treatment for urologic polyneoplasia].

An original method of surgical treatment of synchronous primary-multiple bladder and prostate cancer was used in 10 cases. Ureterocutaneostomy with pelvic-iliac lymphodissection appeared to be the simplest means of urine diversion after cysto-prostate-vesiculoectomy, particularly, in apparent concomitant pathology, basal renal insufficiency or blockade. Urine diversion is best assured via ureterosigmorectoanastomosis which is optimal as far as social rehabilitation of the patient is concerned.

[Genetic and clinical and pathological characteristics of breast cancer in premenopausal and postmenopausal women].

This study involved 525 breast cancer (BC) patients of T2-4N0-2M0 stages at the age of 35 years and older. Significant differences in clinical and pathological characteristics between premenopausal and postmenopausal BC patients were found. Mostly marked differences were shown for positive lymph node correlation with distant metastasis, multicentric growth and local recurrence depending on menopause status. The prevalence of various morphological structures in primary tumors was appeared to be associated with different forms of tumor progression in pre- and postmenopausal women. We have studied polymorphisms in 15 genes involved in major cancer related pathways (apoptosis, interleukins, folate metabolism enzymes genes). We found that variant genotypes of MTHFR and DHFR genes were associated with an increased BC risk among premenopausal women while polymorphism in IL-18, p53 genes were associated with BC among postmenopausal women. These results demonstrate novel biological information, which points the different mechanisms contributed to breast cancer progression in premenopausal and postmenopausal women.

[Investigation of mutations of BRCA1 and BRCA2 genes in 52 breast cancer patients]. / Testirovanie mutatsii genov BRCA1 i BRCA2 u 52 bol'nykh rakom molochnoi zhelezy.

The proportion of BRCA1/2 genes varies widely among populations. We investigated 52 cases of breast cancer: 24 cases of familial breast cancer, 22--early-onset (till 40 years) and 6--bilateral cancer. The frequency of carriers of mutations among familial cancer cases was 16%, among cases of disease till 40 years--9%. 538insC BRCA1 was the most common genetic mutation among hereditary cases of breast cancer.

[99m-Tc-Technetryle mammascintigraphy: clinical protocol and first experience in clinical diagnosis of breast cancer]. / Mammastsintigrafiia s 99mTc-Tekhnitrilom: tekhnika vypolneniia i pervyí opyt klinicheskogo primeneiia pri rake molochoí zhelezy.

Analyzing the results of 99mTc-Technetryle mammascintigraphy in 41 females with breast cancer indicated that polypositional planar mammascintigraphy ensures a high sensitivity (over 88%) in revealing a primary nodule in T1, (more than 95%) in large tumors at above 95% specificity. No nodal accumulation of 99mTc-Technetryle was observed in controls (with fibrocystic mastopathy and suspected coronary heart disease. Mammascintigraphy showed a 85% sensitivity in recognizing axillary lymph nodal metastases too and ascertained that 14 patients had suptaclavicular and subclavian lymph nodal metastases. Therefore, 99mTc-technetryle mammascintigraphy is the method of choice in early detecting a tumorous process, primarily lymphogenic metastasis in breast cancer, and in evaluating its extent.

[Prognostic significance of immunocompetent cell infiltration of breast tumor tissue]. / [Prognosticheskoe znachenie infil'tratsii stromy raka molochnoi zhelezy immunokompetentnymi kletkami.

The prognostic significance of stromal reaction in breast cancer patients has been identified. A reverse correlation between blast lymphocyte level in tumor and metastasis into the regional lymph nodes has been found. Patients with pronounced lympho-histiocytic infiltration receiving combined therapy are expected to have favorable prognosis.

[The extent of the surgical intervention and the prognosis of patients with stage III breast cancer]. / Ob''em operativnogo vmeshatel'stva i prognoz u bol'nykh rakom molochnoi zhelezy III stadii.

The report is concerned with comparison of the effectiveness of surgery for breast tumors (stage III) after Halsted and Patey. The 5-year survival rates, relapse and tumor dissemination proved nearly identical in both study groups. A modified procedure of radical mastectomy after Patey was used for treatment of stage III breast tumors which did not extend through the underlying tissues of the chest wall.

[Therapy and prognosis in Ewing's sarcoma]. / Terapiia i prognoz pri sarkome Iuinga.

The results of treatment of 134 cases of morphologically-verified localized Ewing's sarcoma were evaluated. A comparative analysis showed relapse-free survival to be significantly lower for radiation treatment (23%) than for its combination with various cytostatic drugs. Two-year relapse-free survival rate was as high as 43% in cases receiving sarcolysin or cyclophosphamide as adjuvants. This was matched by 47% for adjuvant adriamycin or carminomycin and 56% for adriamycin plus cyclophosphamide and vincristine. Evaluation of long-term results of adjuvant chemotherapy showed sex, age and site of involvement to be of certain prognostic value.