Abstract
100 Background: To identify prostate cancer (CaP) with high recurrence risk after Radical Prostatectomy (RP) is a challenge. FGFR1 (Fibroblast Growth Factor Receptor 1) plays a critical role in prostate development and tumorigenesis. In this study, we explored the possibility of using FGFR1 fluorescence in situ hybridization (FISH) to predict recurrence after RP in the Formalin fixed paraffin embedded (FFPE) tissue from CaP patients. Methods: FFPE histological specimens from 52 RP cases were evaluated with FGFR1 (8p12) / CEP 8 probe mix. While 32 of the 52 patients recurred within 5 years (PSA progression or death of disease), and 20 remained disease-free with 8 to 15 years. Median age of patients was 62 with Gleason Score range from 4 to 9. Percent of FGFR1 gain and FGFR1 loss per specimen, as well as mean number of FGFR1 signals per specimen were calculated. CEP8 was used as a control to assess hybridization quality. Statistical analysis (Cox Proportional Hazards model) was conducted using SAS 9.2. Results: Survival analysis demonstrated that percent FGFR1 loss in a specimen could identify recurrent CaP with the Harzard Ratio (HR) of 3.34 (p=0.0011), which indicated that the risk of recurrence for FGFR1 loss-positive group is 3.34 times than that for FGFR1 loss-negative group. On the other hand, survival analysis of the percent FGFR1 gain showed that FGFR1 gain (amplification) is favorable for survival with HR of 0.36 (p=0.0043), which indicated that the risk of recurrence for FGFR1 gain-positive group is 0.36 times than that for FGFR1 gain-negative group. By using mean FGFR1 signals per specimen in the Kaplan-Meier analysis, the patient specimens stratified into three distinct groups (overall logrank p=0.0011): normal for FGFR1, FGFR1 gain (more favorable outcome), and FGFR1 loss (highest risk of recurrence). Conclusions: This study shows the utility of FGFR1 copy number abnormalities in CaP. Our results indicate that gain and loss of FGFR1 may have a different effect on disease recurrence. Therefore, FGFR1 FISH may provide predictive value for CaP recurrence in post RP patients, either by itself, or as an adjunct to the currently clinical prognostic indicators.
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