Abstract 3454: High expression of fibroblast growth factor 13 (FGF13) in prostate cancer is associated with a shortened time to biochemical recurrence after radical prostatectomy

Abstract

Fibroblast growth factor homologous factors (FHF1-4) belong to the FGF family involved in prostate cancer. Based on the cBioPortal database (MSKCC, Cancer Cell 2010), FGF13 (FHF2), one of the FHF subfamily members, shows altered mRNA expression in prostate cancer. In this study we aimed to analyze FGF13 expression and functions in prostate cancer. We collected prostate cancer specimens from 234 patients who underwent radical prostatectomy in Turku University Hospital. Frozen tissue was used for qRT-PCR to measure FGF13 mRNA in 76 samples in which glandular or cancer area covered at least 50% of the specimen (non-cancer, n = 31; cancer, n = 45). Tissue microarrays (TMA) containing cancer (n = 152) and adjacent non-cancer (n = 203) samples were examined for FGF13 protein by immunohistochemical staining. Total FGF13 staining score of each TMA core was calculated using HistoScore system. Chi-square test, Kaplan-Meier and Cox proportional hazards regression model were used to analyze the association between FGF13 staining and clinicopathological parameters. Immunofluorescence was used to detect FGF13 localization in prostate cancer cells in vitro. The level of FGF13 mRNA was significantly higher in cancer tissues than in non-cancer tissues (p = 0.0028). FGF13 mRNA levels did not show significant association with the Gleason score, pathologic stage, pre-operation PSA value or PSA failure time. In the TMA study, cancer cells showed weak, moderate or strong cytoplasmic staining for FGF13 in over 99% of the samples whereas luminal epithelial cells were positive in only 53% of the adjacent non-cancer samples. Correspondingly, the cytoplasmic staining of FGF13 presented higher scores in cancer than in non-cancer areas (p<0.001). Moreover, nuclear staining of FGF13 was also observed, and it was more frequent in cancer samples compared to non-cancer samples (59% and 12%, respectively). Especially, basal cells showed positive immunoreactivity sporadically in non-cancer tissues. Only very weak or negative immunostaining of FGF13 was found in stromal cells but interestingly, prominent expression of FGF13 was observed in mononuclear cells. In terms of time to biochemical recurrence after prostatectomy, patients with high FGF13 cytoplasmic staining had a shorter PSA failure free time compared to patients who had lower cytoplasmic FGF13 expression (p = 0.009). Multivariate analysis revealed that high cytoplasmic FGF13 staining (HR = 3.76, 95%CI [1.5-9.3], p = 0.004) was significantly associated with a shorter PSA failure time. Immunofluorescence staining in PC3M cells showed that FGF13 was located to the cytoplasm and nuclei. Overall, our study demonstrates, for the first time, expression and location of FGF13 protein in prostate cancer and suggests that FGF13 could have prognostic value in primary prostate cancer. Citation Format: Lan Yu, Miikka Tuomala, Mervi Toriseva, Teresa Elo, Johanna Tuomela, Heikki Seikkula, Martti Nurmi, Peter Boström, Tuomas Mirtti, Kalle Alanen, Markku Kallajoki, Pirkko Härkönen. High expression of fibroblast growth factor 13 (FGF13) in prostate cancer is associated with a shortened time to biochemical recurrence after radical prostatectomy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3454. doi:10.1158/1538-7445.AM2015-3454