MON-269 FGFR-4 Expression in Pituitary Adenomas Is Associated with Aggressive Tumor Features

Biomarkers predicting tumor aggressiveness in pituitary adenomas have been largely investigated, albeit, with inconsistent results. We investigated the relationship of Fibroblast Growth Factor Receptor-4 (FGFR-4) expression and determined its relationship with radiological, pathological, and clinical parameters. In our study, 650 patients who were followed up for pituitary disease were reviewed from medical charts retrospectively. Of the 307 patients who underwent pituitary surgery for a pituitary adenoma between 2000 and 2015, we selected 161 cases on the basis of availability of pathology specimen of hypophysis tissue in our center. Patients’ radiological, pathological, and clinical parameters were obtained from medical charts. FGFR-4 immunostaining was evaluated using a semiquantitative Histologic score (H score). The mean age of the patients was 56.02 ± 14.80 years. Ninety-two (57.1%) were male and 69 (42.9%) were female. The mean follow-up period was 68.94 ± 44.15 months. Pathological examination revealed the following subtypes; 53 nonfunctioning pituitary adenomas, 26 corticotroph adenomas, 25 hormone receptor negative adenomas, 22 mammotroph adenomas, 13 somatotroph adenomas, 8 combined hormone secreting adenomas, 7 somatomammotroph, and 7 PIT-1 positive adenomas. The mean tumor size was 26.83 ± 14.92 mm. In patients with cavernous sinus invasion, the mean adenoma size was significantly higher than those without (p <0.001). Mean H-score and Ki-67 levels were not different between patients with and without cavernous sinus invasion (p>0.05 for all). The mean H-score, Ki-67, and adenoma size were significantly higher in patients without remission than those with remission (p <0.001, p = 0.014, p <0.001, respectively). The mean H score and adenoma size were significantly higher in patients with residual lesions than those without (p = 0.002, p <0.001; respectively); there was no significant difference in Ki- 67 levels (p>0.05). When the H-score and Ki-67 levels were assessed in terms of gender, sellar-dural invasion, tumor function or presence of poor subtype, no significant difference was detected (p>0.05 for all). The mean H score and adenoma size were significantly higher in patients with Ki-67≥ 3 than those with <3 (p = 0.002, p = 0.004; respectively). There was a weak positive correlation between H-score and Ki-67 (p = 0.005; r = 0.218); on the other hand, Ki-67 was not correlated with mitosis grade, p53 staining, and age, respectively (p>0.05 for all). In our study, we demonstrated that patients with residual lesion and those without remission had high expression of FGFR-4. Also FGFR-4 levels were positively correlated with Ki-67 which itself correlated with lack of remission. Taken together, our results indicate that higher levels of FGFR-4 and Ki-67 in pituitary adenomas might indicate a more aggressive tumor phenotype.