[The first experience of PD-L1 testing of triple negative breast cancer with marker SP142 in Russia]. / Pervyi opyt PD-L1-testirovaniya troinogo negativnogo raka molochnoi zhelezy markerom SP142 v Rossii.

AIM OF STUDY: To evaluate the pecularities of PD-L1 expression in triple negative breast cancer (TNBC) in the Russian population. MATERIALS AND METHODS: For 7 months, within a scientific study of the Russian Society of Clinical Oncology (RUSSCO), we determined the PD-L1 status of 58 patients with TNBC. In each case, an immunohistochemical study was performed in a closed Ventana Bench Mark Ultra automatic stainer using a closed protocol with rabbit monoclonal antibodies Ventana PD-L1 SP142 and Opti View DAB IHC Detection Kit with Opti View Amplification Kit. RESULTS: Positive PD-L1 status in TNBC was detected in 37.93% of cases. Almost all tumors had an expression level of up to 10%. Only 5.17% of cases showed ligand expression on tumor cells. CONCLUSIONS: According to the results of the first experience of testing PD-L1 in TNLM in Russia, it was possible to obtain data comparable to the same data of large international studies. RUSSCO's information and logistic support allows making this analysis available to all citizens of the country.

[Epidemiology and diagnosis of mutations in the ALK gene in patients with non-small cell lung cancer in the Moscow region]. / Epidemiologiya i diagnostika mutatsii v gene ALK u patsientov s nemelkokletochnym rakom legkogo v Moskovskoi oblasti.

AIM OF STUDY: To determine a diagnostic algorithm for detecting translocation of the ALK gene and its frequency in the Moscow region. MATERIALS AND METHODS: During the priod between 2014 and 2018 (inclusive), 488 patients without activating mutations in the EGFR gene in the Moscow region were tested. To detect translocation of the ALK gene, fluorescence in situ hybridization (FISH) methods, an immunohistochemical method, and, in some cases, a polymerase chain reaction were used. RESULTS: Revealed ALK gene rearrangement in a population of patients with lung adenocarcinoma amounted to an average of 7.6% of cases. With this, the main method that we used was immunohistochemical method, applicable in more than 80% of cases. The use of other methods for verification of abnormalities in the ALK gene was found necessary in rare cases (3.3%). CONCLUSIONS: Using the algorithm presented in the article, it was possible to detect ALK gene rearrangement in a population of patients with lung adenocarcinoma in the Moscow region in an average of 7.6% of cases.

Loss of Heterozygosity in BRCA1 and BRCA2 Genes in Patients with Ovarian Cancer and Probability of Its Use for Clinical Classification of Variations.

Changes (or variants) in BRCA1 and BRCA2 gene sequences can have different lengths and clinical significance: from single nucleotide variants (SNV) and short insertions/deletions (<50 bp) to extended deletions and duplications (so-called copy number variations, or CNV). According to their clinical significance, all variants can be divided into pathogenic, likely pathogenic, variants of uncertain significance, likely benign, and benign. Moreover, variants can be germinal (i.e. inherited from parents) and somatic (arising in the process of development of the organism). A specific somatic event is loss of heterozygosity (LOH), i.e. transition of one or many point and short variants from heterozygous to homozygous state. Such an event can be the key to the development of carcinogenesis for cells carrying a pathogenic variant, if we consider it within the framework of the Knudson's two-hit carcinogenesis theory. We studied the prevalence and nature of LOH in of ovarian cancer samples carrying or not carrying a pathogenic variant. To this end, a full coding sequence of BRCA1/2 genes was determined in 30 pairs of DNA samples isolated from blood cells and paraffinized histological blocks of patients on a MiSeq Illumina instrument. Analyss of the obtained reads revealed 9 pathogenic point and short variants (30% patients): 6 germinal (20%) and 3 somatic (10%), and 8 somatic CNV (3 deletions and 5 duplications of several or all exons of the BRCA1 gene). LOH was detected in 70% patients; among the carriers of pathogenic variants - in 83%. For pathogenic variants, the percentage of reads with the alternative allele increased more often than for benign variants located in another gene, or detected in other patients (67% vs. 44%). However, the difference was statistically insignificant, which can be due to insufficient number of patients. Only in 3 of 21 cases of LOH (14%), it can be attributed to CNV. In other cases, LOH is most likely determined by gene conversion, but further research is needed.

[Genetic risk factors for sporadic germ cell testicular tumors].

INTRODUCTION: Approximately 95% of all testicular cancers are testicular germ cell tumors (GCTTs), represented by seminoma and nonseminoma germ cell testicular cancer. There is a hypothesis that the formation of GCTTs begins in early embryogenesis being a part of testicular dysgenesis syndrome (TDS). AIM: To determine the role of genetic factors in the development of GCTTs. MATERIALS AND METHODS: We studied the frequency of alleles and genotypes KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876) and BAK1 (rs210138) in 97 fertile men (control), and 73 patients with GCTTs (34 seminoma and 39 nonseminoma). RESULTS: GCTTs were statistically significantly associated with KITLG rs1508595 gene (p=0.0003 for allele G, p=0.0014 for genotype GG), and with rs995030 gene (p=0.0031 for genotype GG). When comparing patients with seminoma and control group, statistically significant differences were found for SPRY4 rs4624820 (p=0.0226 for the A and p=0.04 for the AA), for KITLG rs995030 (p=0.0375 for the G and p=0.0282 for GG), rs1508595 (p=0.0306 for G), for BAK1 rs210138 (p=0.0329 for the G and p=0.0219 for the GG). When comparing patients with nonseminoma and fertile men, statistically significant differences were found only for KITLG rs1508595 (p=0.0005 for the G and p=0.0021 for the GG). There was no statistically significant difference between the allele and genotype frequencies of the investigated genes from seminoma and nonseminoma GCTTs patients. However, these groups differed statistically significantly when genotype combinations of the three genes were investigated (p=0,029; OR 3,709 [1.147-11.99]). The combination of genotypes of the three genes was found to increase the risk of GCTTs by 6.5 times (p=0.0005; OR 6.526 [2.078-20.5], and the risk for seminoma was over 12-fold (p<0.0001; OR 12,68 [3,731-43,11]. CONCLUSION: A comprehensive study of genotypes associated with GCTTs in patients with manifested TDS can be used for risk stratification to identify and follow-up high-risk patients, develop approaches to family counseling and treatment, which is the basis for predictive medicine.

[ERCC1 as a Marker of Ovarian Cancer Resistance to Platinum Drugs].

The review is concerned with the crucial marker of nucleotide excision repair ERCC1 and its contribution to platinum resistance of ovarian cancer. All the variants of the laboratory and clinical ERCC1 assessment in the ovarian cancer tissue (single nucleotide polymorphisms of the ERCC1 gene, levels of mRNA or protein) are considered. Data on the prognostic and predictive value of ERCC1 as a marker of the response to platinum-based therapy in ovarian cancer are systematized. The authors discuss the possible causes of heterogeneity of the results and emphasize the necessity of a unified and integrated approach to evaluation of ERCC1 in the tumor. The publications cited in the Search Engine Pub Med up to January 2015 were analyzed.

Analysis of circulating tumor cells in patients with triple negative breast cancer during preoperative chemotherapy.

The presence of circulating tumor cells in the blood of patients with triple negative breast cancer (early and locally advanced cancer) before and after preoperative chemotherapy was assessed using expression markers. Before therapy, circulating tumor cells were detected in 5 of 13 (38%) patients with early cancer and in 7 of 17 (41.2%) patients with locally advanced cancer. After therapy, the circulating immune cells were detected in one patient with locally advanced cancer, who had no circulating cells before therapy. The tumor was resistant to chemotherapy and the disease progressed. The detected circulating tumor cells were HER-2-positive, while the primary tumor was HER-2-negative. It was concluded that the circulating immune cells can be a potential marker of the efficiency of therapy and predictors of the disease course, while their phenotype can differ from the phenotype of the primary tumor.

Tartrate-resistant acid phosphatase as a marker of bone metastases in patients with breast cancer and prostate cancer.

Serum activity of tartrate-resistant acid phosphatase 5b (TRAP 5b) in patients with breast cancer and prostate cancer having bone metastases was much higher than in healthy donors and patients without skeletal injuries. TRAP 5b activity in patients with breast cancer and multiple bone metastases surpassed that in patients with single bone metastases. The mean activity of TRAP 5b and range of enzyme activity in women treated with bisphosphonates were significantly lower than in patients not receiving antiresorptive therapy. Diagnostic sensitivity and specificity of TRAP 5b as a marker of skeletal metastases in patients with breast cancer were 82 and 87%, respectively. In patients with prostate cancer these indexes were 71 and 83.4%, respectively. Detection of this marker in tumor patients holds much promise for early diagnostics of bone metastases, estimation of the severity of skeletal metastases, and monitoring of the efficiency of bisphosphonate therapy.

Efficacy of combination chemotherapy including Platidiam in the treatment of malignant testicular tumors.

Thirty-seven patients were treated for advanced malignant testicular tumors with combined chemotherapy including cis-platinum (Platidiam). A complete regression was achieved in 23 patients (62%). No severe side effects were observed. Also in this study the effectivity of cis-platinum in the treatment of testicular tumors was proved.