2025 Proffered Presentations
S041: P53 IMMUNOPOSITIVITY IS ASSOCIATED WITH FUNCTIONAL STATUS IN A LARGE COHORT OF 663 PITUITARY ADENOMA PATIENTS
Kaasinath P Balagurunath, BA1; Christopher S Hong, MD1; Jakob V Gerstl, MBBS1; Ryan Chrenek, MD1; Sean Lyne, MD1; Noah L Nawabi, BS1; Rania A Mekary, PhD2; Timothy R Smith, MD, PhD1; 1Brigham and Women's Hospital; 2School of Pharmacy, Massachusetts College of Pharmacy and Health Sciences (MCPHS) University
Introduction: The immunohistochemical accumulation of p53 is well documented to be associated with worse outcomes in numerous malignancies. Previous literature has demonstrated that atypical pituitary adenomas, which often exhibit immunohistochemistry (IHC) staining positive for p53, tend to follow more aggressive courses and exhibit worse postoperative outcomes. However, there are no large-scale retrospective studies characterizing the association of p53 with pituitary adenoma functional status.
Objectives: To determine the predictive value of p53+ IHC staining as it relates to hormone immunopositivity.
Methods: In this single institution, retrospective study, a large cohort of patients diagnosed with pituitary adenomas were categorized as p53 positive or negative on the basis of tumor immunohistochemical staining. Lesion, surgical approach, clinical, and endocrinological characteristics at baseline and postoperatively were tracked. Hormone values were determined at baseline and up to 3 years postoperatively. Pituitary adenoma size, location, and dimensions were determined using preoperative magnetic-resonance-imaging (MRI) and computerized-tomography (CT) imaging. T tests and chi-square tests were not performed due to the high type-1 error rate. A multivariate logistic regression model was created to identify the hormones likely to co-stain with p53.
Results: A total of 663 patients receiving TSS for pituitary adenomas from 2008-2019 were included, 337 (50.8%) of which exhibited p53 immunopositivity. The most common preoperative symptoms were headache, which occurred more often in P53+ patients, (48.7% vs 40.2%, in p53+ vs p53- patients respectively) and visual loss (36.5% vs 35.6%). Patients with p53+ tumors were less likely to present with fat deposition (3.9% vs 7.7%), and to be on desmopressin preoperatively (0.3% vs 2.5%).
p53+ lesions experienced lower rates of parasellar location (3.8% vs 14.4%), but tended to present with higher MIB indices (3.9 ± 3.8 vs 2.5 ± 2.1) and atypical staining tumors (11.6% vs 2.3%). A majority of tumors were intrasellar (96.2% vs 94% in p53+ vs p53-) or suprasellar (59% vs 61.1%) macroadenomas (83.6% vs 84.8). p53+ tumors experienced lower rates of microscopic approach (5.3% vs 9.3%). They also presented with higher rates of preoperative hyperprolactinemia (44.6% vs 34.8%) and low ADH (29.7% vs 10.6%).
p53+ tumors experienced higher rates of gross total resection (GTR) (78.4% vs 63.6%), and postoperatively, several types of hormone dysfunction including hyponatremia and high HGH levels were more common in the p53+ cohort. The rates of common complications such as transient diabetes insipidus and intraoperative CSF leaks did not differ between groups. There were no other differences in postoperative outcomes.
Multiple logistic regression demonstrated that prolactin+, and plurinominal lesions were significantly more likely to be p53+ as compared to a reference group of non-functional pituitary adenomas with IHC negative for all hormones.
Conclusions: Overall, tumors staining positive for p53 presented with distinctive preoperative clinical and endocrine characteristics, and p53 immunopositivity was associated with prolactin immunopositivity, and plurihormonality.
