I Tsimafeyeu1, A Khasanova2, E Stepanova3, M Gordiev2, D Khochenkov3, A Naumova4, I Varlamov5, A Snegovoy3, L Demidov3. 1. Kidney Cancer Research Bureau, Bazovskaya ul. 4/1 of. 15, Moscow, 125635, Russia. office@kidneytumor.org. 2. Tatarstan Regional Cancer Center, Kazan, Russia. 3. N.N. Blokhin Russian Cancer Research Center, Moscow, Russia. 4. Kidney Cancer Research Bureau, Bazovskaya ul. 4/1 of. 15, Moscow, 125635, Russia. 5. Altai Regional Cancer Center, Barnaul, Russia.
Abstract
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.
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 pRCCpatients 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). FGFR2S252W 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.
Authors: W Marston Linehan; Gennady Bratslavsky; Peter A Pinto; Laura S Schmidt; Len Neckers; Donald P Bottaro; Ramaprasad Srinivasan Journal: Annu Rev Med Date: 2010 Impact factor: 13.739