[Study of FGFR2 status in gastric cancer by immunohistochemistry and fluorescent in situ hybridization]. / Izuchenie statusa FGFR2 pri rake zheludka metodami immunogistokhimii i flyuorestsentnoi gibridizatsii in situ.

BACKGROUND: Assessment of FGFR2 status in gastric cancer is an important task, without clarification of which it is impossible to identify a cohort of patients in whom the best response to treatment with anti-FGFR2 drugs could be obtained. OBJECTIVE: To conduct a comparative analysis of the expression and amplification of the FGFR2 gene in gastric cancer in primary tumors and metastases in the lymph nodes. MATERIAL AND METHODS: FGFR2 status was studied in 61 patients with stage III gastric adenocarcinoma using an immunohistochemical method (Abcam clone EPR24075-418, R&D clone 98706, Santa Cruz clone C-8, Abcam clone 1G3) and FISH. RESULTS: The antibody Abcam clone EPR24075-418 was found satisfactory for the immunohistochemical study of FGFR2. FGFR2 expression was detected in 26 (43%) cases, amplification in 5 (8%) cases. Amplification of FGFR2 in 4 cases out of 5 was accompanied by the expression of 3+, in 1 case - 2+. Discordance between FGFR2 expression in primary tumor and lymph node metastases was revealed in 13 (21%) cases. CONCLUSION: Clone EPR24075-418 showed the best result in assessing the expression of FGFR2: the correlation with FISH results in reaction 3+ was 100%. Due to the high heterogeneity of FGFR2 expression, it is recommended to either examine the material of the primary tumor and metastasis, or evaluate a large volume of the primary tumor.

The Novel Diagnostic Index Based on HLA-DRB1 Genotype and PD-L1 Expression can Predict Severe irAEs in Patients with Metastatic Melanoma Taking Immune Checkpoint Inhibitors. The Results of the Pilot Study.

Immune-related adverse events (irAEs) occur in up to 50% of patients treated with an anti-CTLA-4 antibody and 30% of patients treated with PD-1/PD-L1 antibodies. Severe forms of toxicity are observed in 3% of patients and require systemic steroid therapy and constant monitoring. One of the considered predictor biomarkers of irAEs development is HLA-genotypes. This research aims to evaluate the diagnostic significance of HLA-DRB1 genotypes and other clinical and laboratory parameters to predict the development of irAEs. The study involved 28 patients with metastatic melanoma taking checkpoint inhibitors therapy [nivo 53.6%, Ipi+nivo 32.1%, other (pembro, prolgo) 14.3%]. The PD-L1 expression and HLA-DRB1 genotype were evaluated. After 2-3 months the development of irAES was assessed. The complications of 3-4 grade or multi-organ damage were termed as severe irAEs. Various IrAEs developed in 57.1% (16/28) of patients, while severe irAEs occurred in 35.7% (10/28). Among all patients, HLA-DRB1 genotypes associated with the risk of autoimmune diseases were found in 78.5% (22/28). The PD-L1 expression was detected in 60.7% (17/28) of individuals. Combination treatment increases the risk of toxicity, p = 0.0028, with a diagnostic sensitivity of 56% and a diagnostic specificity of 100% (RR = 2.71, OR = 31.67). An index based on the parameters studied (HLA-DRB1, absence of PD-L1 expression, and type of treatment) was created. It allows assuming the risk of developing severe irAES (p = 0.0126). When comparing this indicator between irAEs 1-2 and irAEs 3-4, the presence of an index value of more than 2 gives a sensitivity for predicting severe toxicity of 40.00% and a specificity of 83.33%.

Role of C-reactive protein concentration of blood plasma in assessment of the severity and the effectiveness of treatment in patients with squamous cell carcinoma of the oral cavity mucosa.

The purpose of this study was to determine the prognostic significance of dynamics of C-reactive protein concentration in blood plasma as a marker for the progression of squamous cell carcinoma of the oral cavity mucosa. From January 2014 to August 2014 there were under the observation 35 patients with squamous cell carcinoma of the oral cavity mucosa. All patients were divided into 2 groups: group 1 - primary patients who had been diagnosed with malignant lesions of the oral cavity mucosa for the first time (17 people); group 2 - patients with recurrent disease (18 people). All 17 patients of group 1 received induction polychemotherapy by PF scheme and 18 patients of group 2 - curative polychemotherapy by the following schemes: PF, DCF, TC. In all patients there was performed an assessment of the level of C-reactive protein in blood serum at the stage prior to drug treatment and before each subsequent cycle of chemotherapy. An assessment of the level of C-reactive protein before treatment showed that in 17 patients of group 1 its level was in the normal range. Patients of group 2 had an increased concentration of C-reactive protein in blood plasma. Analysis of obtained data allows concluding that the level of C-reactive protein may be effectively used as a prognostic marker in patients with this pathology.