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 (AU)

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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.

[Determination of EGFR gene somatic mutations in tissues and plasma of patients with advanced non-small cell lung cancer]. / Opredelenie somaticheskikh mutatsii v gene EGFR v tkaniakh i plazme bol'nykh nemelkokletochnym rakom legkogo.

The presence of activating mutations in the EGFR gene influences cell proliferation, angiogenesis, and increases metastatic ability; it has a significant impact on the choice of medical therapy of non-small cell lung cancer (NSCLC). The use of targeted therapy with tyrosine kinase inhibitors requires performance of appropriate genetic tests. The aim of this study was to design a real-time PCR-based diagnostic kit for fast and cheap of EGFR mutations testing in paraffin blocks and plasma, and kit validation using samples from patients with NSCLC, and also comparative estimation of diagnostic features of real-time PCR with wild type blocking and digital PCR for mutation testing in blood plasma. The study included 156 patients with various types of adenocarcinoma differentiation. It was designed a simple and efficient real-time PCR-based method of detecting L858R activating mutation and del19 deletion in the EGFR gene for DNA isolated from paraffin blocks. Kit for EGFR mutations was validated using 411 samples of paraffin blocks. The proposed system showed high efficiency for DNA testing from paraffin blocks: a concordance with results of testing with therascreen® EGFR RGQ PCR Kit ("Qiagen", Germany) was 100%. It has been shown the possibility of using this test system for the detection of mutations in plasma.