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 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.

Background: Pituitary adenomas are slow-growing tumors that originate from the anterior part of the pituitary gland. These tumors are associated with dysregulation of a number of long non-coding RNAs (lncRNAs). Metastasis-associated lung adenocarcinoma transcript-1 ( MALAT-1 ) is a long non-coding RNA (lncRNA) that has been implicated in the regulation of cell proliferation, gene expression, apoptosis, differentiation, and cell cycle transition in various tumors, including pituitary adenomas (PA). Objective: To evaluate the impact of MALAT1 gene variants (rs3200401, rs619586, and rs1194338) and immunohistochemical markers (Ki-67 and p53) on the susceptibility and clinical characteristics of PA. Methods: a case-control study included patients with PA and age- and gender-matched controls. PA diagnosis was confirmed through MRI/CT imaging and/or histopathological examination. DNA was extracted from peripheral blood samples, and three MALAT1 variants (rs3200401, rs619586, and rs1194338) were genotyped using TaqMan ^® real-time PCR. The expression of Ki-67 and p53 were evaluated immunohistochemically using digital image analysis. Statistical analyses included chi-square tests to compare genotype and allele distributions, logistic regression to estimate PA risk (odds ratios, 95% confidence intervals), and nonparametric tests for biomarker evaluation. Results: Among 390 participants (145 PA and 245 controls), only the MALAT1 rs619586 variant showed statistically significant associations after Bonferroni correction (p < 0.016). The rs619586 G allele was more frequent in PA patients than in controls (4.1% vs. 0.8%, p = 0.001) and increased the odds of developing PA by 4.1-fold under the additive model (OR = 4.139, 95% CI: 1.365- 12.551, p = 0.012). The G allele remained significantly associated across several clinical subgroups, including microadenomas, macroadenomas, invasive PAs, and PAs with recurrence (p ≤ 0.015). In PA tissues, p53 H-scores were higher in macroadenomas compared with microadenomas (p = 0.047), and patients with the rs619586 AA genotype showed significantly higher p53 expression than those with the AG genotype (p = 0.008). A moderate positive correlation was observed between Ki-67 LI and p53 expression (ρ = 0.268, p = 0.035). Conclusions: MALAT1 rs619586 G allele is significantly associated with an increased risk of PA and its more aggressive clinical features, including invasiveness and recurrence. These findings suggest that rs619586 may serve as a potential genetic marker linked to PA susceptibility. Additionally, the observed relationship between p53 expression and tumor proliferation highlights its potential role in PA tumorigenesis. Further studies are needed to confirm these associations and clarify the underlying molecular mechanisms.