[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.

[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.

FGFR2 overexpression predicts survival outcome in patients with metastatic papillary renal cell carcinoma.

BACKGROUND: Up to date, there are no data about FGFR2 expression and its predictive role in papillary RCC (pRCC) patients. The aim of the present study was to test FGFR2 expression and mutations for association with survival outcome in patients with pRCC. METHODS: Specimens of removed primary tumors from 214 untreated metastatic pRCC patients were evaluated by immunohistochemistry with FGFR2 antibody. FGFR2 mutations were assessed by PCR and direct sequencing, with DNA obtained from 62 paraffin-embedded pRCC samples. FGFR2 expression was tested for associations with progression-free survival (PFS), overall survival (OS) and best objective response. RESULTS: Expression of FGFR2 was observed in 23 % (49/214) of primary pRCC, mostly in cytoplasm of tumor cells. Expression of FGFR2 was significant lower in normal tissue of kidney (1 %, P = 0.001). FGFR2 S252W mutation was found in one patient (1.6 %), and no N549K mutation was detected. FGFR2 expression was strongly associated with a number of metastatic sites, type 2 of pRCC, lower nucleolar grade (P < 0.001). FGFR2-positive patients had significantly shorter OS and PFS (P < 0.05). On multivariate analysis, FGFR2 expression, MSKCC risk group and type of pRCC were found to be independent predictors of survival. CONCLUSIONS: In this study, we described immunohistochemical expression of FGFR2 in a large series of pRCC specimens. FGFR2 expression was found to be prognostic factor for survival in patients with metastatic pRCC. FGFR2 mutations are rare across papillary types of RCC.

[Sunitinib: 10 years after approval for the therapy of metastatic renal cell carcinoma].

Sunitinib is one of first targeted agents and tyrosine kinase inhibitors of vascular endothelial growth factor receptor (VEGFR) that approved for therapy of metastatic renal cell carcinoma. -Moreover it is among the first compounds in oncology registered after Phase 2 of clinical trials. Sunitinib was used in the United States since January 2006. For the past 10 years a wide experience of sunitinib administration has been accumulated both in practice and in clinical trials. This review summarizes the results of sunitinib studies.