Prognostic Molecular and Biological Characteristics of Phyllodes Tumors of the Breast.

Prognosis for some histological variants of a rare breast disease, phyllodes tumors, is evaluated. The prognostic potential of some molecular biological factors significantly correlating with breast cancer prognosis is evaluated on a unique clinical material (244 cases with benign, intermediate, and malignant phyllodes tumors). The development of benign phyllodes tumor relapse directly correlated with the number of G0/1-phase cells and inversely correlated with the number of cells in the G2+M and S phases. The level of steroid hormone receptors in phyllodes tumors cannot serve as a prognostic marker predicting the disease course. The presence of somatic mutations of TP53 gene and loss of heterozygosity of specific intragenic loci in the tumor correlate with the development of disease relapse (p<0.05).

[Smooth muscle tumors of uncertain malignant potential]. / Gladkomyshechnye opukholi s neopredelennym zlokachestvennym potentsialom.

OBJECTIVE: To investigate microsatellite instability in smooth muscle tumors of uncertain malignant potential and to compare the results with clinical and morphological data. SUBJECT AND METHODS: Histological and immunohistochemical studies were conducted in 26 patients aged 30-63 years (mean age, 37 years) with leiomyomatosis; which revealed intravenous leiomyomatosis in 20 cases, metastasizing leiomyoma in 2, disseminated peritoneal leiomyomatosis in 3, and smooth muscle tumor of uncertain malignant potential in 1 case. Microsatellite instability was studied by fragment analysis on a genetic analyzer using a test system of six markers: D10S1146, D10S218, D10S24, D10S1213, D3S1295, and D9S942. RESULTS: Microsatellite repeat changes characteristic of leiomyosarcomas (heterozygosity loss and/or microsatellite instability in at least one locus studied) were found in 6 patients; all were clinically and morphologically diagnosed as having intravenous leiomyomatosis. In 3 of these 6 cases, leiomyomatosis was accompanied by metastases to the lungs and spread to the peritoneum; heart damage was noted in 2 cases. The data analysis did not allow identification of any significant clinical and morphological criteria for this group. CONCLUSION: Leiomyomatosis is not a transitional form from benign leiomyoma to leiomyosarcoma, as evidenced by the difference in the status of molecular markers. Analysis of molecular genetic changes in DNA from tumor tissue samples cannot categorically clarify the nature of the disease by identifying the signs of genetic instability; however, there is a need for further accumulation of experience in studying tumors of this group and in identifying the possible association with disease prognosis.

Clinical Significance of Matrix Metalloproteinases in Blood Plasma of Patients with Gastric Cancer.

Plasma levels of MMP-2, MMP-7, and MMP-9 and their tissue inhibitor TIMP-2 were measured in 89 patients with gastric cancer and the relationship between these parameters and the main clinical morphological characteristics of the disease was analyzed. Plasma levels of the proteins were measured using standard direct ELISA kits. The level of MMP-7 in patients with gastric cancer was significantly higher than in the control group (medians 2.7 and 1.2 ng/ml, respectively; p<0.01), but only in 51% patients this parameter surpassed the upper threshold normal value (2.35 ng/ml; 95% percentile of control). The level of MMP-9 in gastric cancer patients was lower than in control group by 1.6 times (medians 167 and 267 ng/ml, respectively; p<0.01). Plasma levels of MMP-2 and TIMP-2 in patients with gastric cancer and healthy subjects were similar. No appreciable associations of plasma matrixins and TIMP-2 with the main clinical morphological characteristics of the disease were detected. The patients were followed up for 8 to 85 months (median 70.8 months). Low level of MMP-2 and high level of MMP-7 in the plasma proved to be unfavorable prognostic factors for overall survival. At MMP-2<268 ng/ml, the 5-year overall survival was 32% vs. 60% for patients with the marker level higher than this threshold value (p=0.016). The differences in overall survival in relation to their MMP-7 levels for 5-year observation did not surpass 16% (39% at marker level >2.7 ng/ml and 55% at lower level; p=0.048). Plasma levels of MMP-2 and TIMP-2 were not significantly associated with overall survival. Multivariate analysis showed that only T index (p=0.034) and plasma MMP-7 level (p=0.007) were essential for overall survival. The increase in plasma or serum MMP-7 levels is a universal phenomenon in tumors of different histogenesis, which precluded the use of this parameter as a specific diagnostic marker of gastric cancer. At the same time, it could be useful for monitoring the treatment efficiency and detection of relapses. In addition, high plasma level of MMP-7 remained an independent factor of unfavorable prognosis for overall survival of patients with gastric cancer.

Flow cytometric analysis of the ERCC1, marker of DNA damage repair, in the tumor specimens embedded into paraffin blocks.

The differences in expression of ERCC1 were estimated between tumor specimens embedded into paraffin blocks and surgical biopsy specimens of non-small cell lung cancer as well as breast and ovarian cancers. Concordance or differences not higher than 20% were observed in 73% of the cases. The number of the cases with more significant differences in ERCC1 expression was less than 17%. The results show that ERCC1 detection in surgical biopsy specimens by flow cytometry is the more preferable method due to reduced preanalytical phase of the analysis.

[Search for potential gastric cancer biomarkers using low molecular weight blood plasma proteome profiling by mass spectrometry].

Gastric cancer, one of the most widespread malignant tumors, still lacks reliable serum/plasma biomarkers of its early detection. In this study we have developed, unified, and tested a new methodology for search of gastric cancer biomarkers based on profiling of low molecular weight proteome (LMWP) (1-17 kDa). This approach included three main components: sample pre-fractionation, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), data analysis by a bioinformatics software package. Applicability and perspectives of the developed approach for detection of potential gastric cancer markers during LMWP analysis have been demonstrated using 69 plasma samples from patients with gastric cancer (stages I-IV) and 238 control samples. The study revealed peptides/polypeptides, which may be potentially used for detection of this pathology.

[Combined operations by retroperitoneal liposarcomas].

Retrospective analysis of 228 patients with retroperitoneal liposarcoma, operated on in the Russian Oncology Center during 1971-2010, has been done. Of 223 performed operations, 124 were combined, i.e., required multi-organ resection. The kidney was the most frequently removed organ both in cases of primary and recurrent tumors. 10-year survival rate was 26% after combined operations and 35% after surgery, they did not need the multiorgan resection.