Study of major genetic factors involved in pituitary tumorigenesis and their impact on clinical and biological characteristics of sporadic somatotropinomas and non-functioning pituitary adenomas

Genetic and functional aberrations of guanine nucleotide-binding protein, alpha stimulating (GNAS), aryl hydrocarbon receptor interacting protein (AIP), and pituitary tumor transforming gene (PTTG) are among the most prominent events in pituitary tumorigenesis. A cohort of Brazilian patients with somatotropinomas (n=41) and non-functioning pituitary adenomas (NFPA, n=21) from a single tertiary-referral center were evaluated for GNAS and AIP mutations and gene expression of AIP and PTTG. Results were compared to the clinical and biological (Ki67 and p53 expression) characteristics of tumors and their response to therapy, if applicable. Genetic analysis revealed that 27% of somatotropinomas and 4.8% of NFPA harbored GNAS mutations (P=0.05). However, no differences were observed in clinical characteristics, tumor extension, response to somatostatin analog therapy, hormonal/surgical remission rates, Ki67 index, and p53 expression between mutated and non-mutated somatotropinomas patients. PTTG overexpression (RQ mean=10.6, min=4.39, max=11.9) and AIP underexpression (RQ mean=0.56, min=0.46-max=0.92) were found in virtually all cases without a statistically significant relationship with clinical and biological tumor features. No patients exhibited somatic or germline pathogenic AIP mutations. In conclusion, mutations in GNAS and abnormal PTTG and AIP expression had no impact on tumor features and treatment outcomes in this cohort. Our data support some previous studies and point to the need for further investigations, probably involving epigenetic and transcriptome analysis, to improve our understanding of pituitary tumor behavior.

Analysis of factors influencing short-term effect of presurgical pharmacological therapy and transsphenoidal microsurgery for somatotropinomas / 实用医学杂志

Objective To analyze factors influencing short-term effect of presurgical pharmacological thera-py and transsphenoidal microsurgery for somatotropinomas. Methods The clinical data of 53 patients underwent presurgical pharmacological therapy and transsphenoidal surgery for somatotropinomas were retrospectively analyzed in order to search for factors influencing effect of presurgical pharmacological therapy and transsphenoidal surgery for somatotropinomas. Results Serum GH inhibition rates decreased<50.00%from baseline in 62.26%of patients receiving presurgical pharmacological therapy. Statistical analysis concerning the influence of sex , neuropathological evaluation, tumor size and presence of invasion on presurgical pharmacological therapy effect were performed using a chi-squared test, no significant correlation was found among these factors and presurgical pharmacological therapy effect. Total remission rates were 43.40%, Statistical analysis concerning the influence of sex , neuropathological e valuation, tumor size, presence of invasion and presurgical pharmacological therapy effect on remission rate were performed using a chi-squared test, a significant correlation was found among tumor size, presence of invasion, presurgical pharmacological therapy effect and remission rate , while no significant correlation was found among the rest of the factors. Further Logistic regression analysis demonstrated a significant correlation among tumor size , presence of invasion and remission rate , while no significant correlation was found between presurgical pharmacolog-ical therapy effect and remission rate. Conclusions Presurgical pharmacological therapy effect revealed no signifi-cant correlation with sex, neuropathological evaluation, tumor size or presence of invasion. Total remission rate cor-related with tumor size and presence of invasion. A better presurgical pharmacological therapy effect may indicated a better outcome, while postoperative remission rate revealed no significant correlation with presurgical pharmacologi-cal therapy in our series.