Insights into FGFR4 (rs351855 and rs7708357) Gene Variants, Ki-67 and p53 in Pituitary Adenoma Pathophysiology

• Published in: International journal of molecular sciences Vol. 26; no. 15; p. 7565
• Main Authors: Juskiene, Martyna, Duseikaite, Monika, Vilkeviciute, Alvita, Karinauske, Egle, Baikstiene, Ieva, Makstiene, Jurgita, Poskiene, Lina, Tamasauskas, Arimantas, Liutkeviciene, Rasa, Verkauskiene, Rasa, Zilaitiene, Birute
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.08.2025; MDPI
• Subjects: Adenoma - genetics; Adenoma - metabolism; Adenoma - pathology; Adenoma - physiopathology; Adult; Aged; Alleles; Case-Control Studies; Cell cycle; Female; Females; Genetic Predisposition to Disease; Genotype; Humans; Ki-67 Antigen - genetics; Ki-67 Antigen - metabolism; Male; Males; Middle Aged; Pituitary Neoplasms - genetics; Pituitary Neoplasms - metabolism; Pituitary Neoplasms - pathology; Pituitary Neoplasms - physiopathology; Polymorphism, Single Nucleotide; Proteins; Receptor, Fibroblast Growth Factor, Type 4 - blood; Receptor, Fibroblast Growth Factor, Type 4 - genetics; Regression analysis; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumors; Ki-67; pituitary adenoma; FGFR4 (rs351855 and rs7708357); gene variants; ELISA; p53
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms26157565

To determine the association between FGFR4 (rs351855 and rs7708357) gene variants, serum levels, and immunohistochemical markers (Ki-67 and p53) in pituitary adenoma (PA), a case-control study was conducted involving 300 subjects divided into two groups: the control group (n = 200) and a group of PA (n = 100). The genotyping of FGFR4 rs351855 and rs7708357 was carried out using the real-time polymerase chain reaction (RT-PCR) method. The serum FGFR4 levels were measured using the ELISA method. Immunohistochemical analysis (Ki-67 and p53) was conducted. Statistical analysis of the data was performed using IBM SPSS Statistics 30.0 software. There were no statistically significant differences after analyzing the genotypes and alleles of FGFR4 rs351855 and rs7708357 in patients with PA and control groups (all p > 0.05). After evaluating the distribution of genotypes and alleles of FGFR4 rs351855 and rs7708357 in micro/macro, invasiveness, activity, and recurrence of PA and the control groups, the analysis showed no statistically significant differences between the groups (p > 0.05). Similarly, no significant differences in FGFR4 levels were observed between PA patients and control group (median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, p = 0.121). Immunohistochemistry for Ki-67 revealed a labeling index (LI) of <1% in 25.5% of patients with PA, an LI of 1% in 10.9%, and an LI of >1% in 63.6% of patients. Further analyses showed no statistically significant associations with tumor size, invasiveness, activity, or recurrence. Immunohistochemistry for p53 revealed that macroadenomas had a significantly higher p53 H-score compared to microadenomas (median (IQR): 30.33 (28.68) vs. 18.34 (17.65), p = 0.005). Additionally, a moderate, statistically significant positive correlation between the Ki-67 LI and the p53 expression was found (Spearman’s ρ = 0.443, p = 0.003, n = 43). FGFR4 variants and serum protein levels were not significantly associated with PA risk or tumor features. Conversely, immunohistochemical markers Ki-67 and p53 were more informative, with higher p53 expression in macroadenomas and a moderate positive correlation between Ki-67 and p53, highlighting their potential relevance in tumor growth assessment.