2025 Proffered Presentations
S003: PROGNOSTIC SIGNIFICANCE OF P53 IMMUNOPOSITIVITY IN A LARGE COHORT OF PITUITARY ADENOMA PATIENTS RECEIVING TRANSSPHENOIDAL SURGERY
Kaasinath Balagurunath, BA; Christopher S Hong, MD; Jakob V Gerstl, MD; Ryan Chrenek, MD; Sean Lyne, MD; Noah L Nawabi, BS; Timothy R Smith, MD, PhD; Brigham and Women's Hospital
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 examining the outcomes, lesion characteristics, and factors predictive of complication in patients with p53 immunopositive pituitary adenomas.
Objectives: To characterize the clinical outcomes and factors predictive of complications in patients with symptomatic pituitary adenomas, with verified p53 positive IHC staining, receiving transsphenoidal surgery (TSS).
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.
Results: A total of 663 patients receiving TSS for pituitary adenomas from 2008-2019 were included, 337 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, p=0.03) and visual loss (36.5% vs 35.6%, p=0.81). Patients with p53+ tumors were less likely to present with fat deposition (3.9% vs 7.7%, p=0.04), and to be on desmopressin preoperatively (0.3% vs 2.5%, p=0.02).
p53+ patients were less likely to develop parasellar tumors (3.8% vs 14.4%, p<0.001), but tended to present with higher MIB indices (p<0.001) and atypical staining tumors (11.6% vs 2.3%, p<0.001). Most tumors were intrasellar (96.2% vs 94%, p=0.2) or suprasellar (59% vs 61.1%, p=0.61) macroadenomas (83.6% vs 84.8%, p=0.07). p53+ tumors were marginally less likely to be operated on through a microsurgical approach (p=0.055), and were less likely to receive nasal packing (29.7% vs 44%, p<0.001). These tumors tended to co-stain with FSH (p=0.013), HGH (p=0.05), and prolactin (p<0.001). Similarly, p53+ lesions were more likely to present with preoperative hyperprolactinemia (44.6% vs 34.8%, p=0.01) and low ADH (p=0.007).
Interestingly, p53+ tumors experienced higher rates of gross total resection (GTR) (p=0.003). Postoperatively, hyponatremia and high HGH levels were more common in the p53+ cohort (p=0.02 for all). The incidence of common complications such as transient diabetes insipidus and intraoperative CSF leaks did not differ between groups, however the incidence of meningitis and the requirement of postoperative cortisol replacement were more common among patients with p53+ tumors (p=0.05, p=0.03 respectively). There were no other differences in postoperative outcomes.
Multiple logistic regression demonstrated that p53+ staining was not necessarily predictive of GTR, postoperative dysnatremias, infection incidence, or complication incidence. Furthermore, the usage of intraoperative nasal packing was the only factor predictive of p53+ staining.
Conclusion: Overall, tumors staining positive for p53 presented with distinctive preoperative clinical and lesion characteristics, but p53 immunopositivity was not necessarily predictive of worse postoperative outcomes.
