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The impact of immunohistochemical markers of Ki-67 and p53 on the long-term outcome of growth hormone-secreting pituitary adenomas: A cohort study

Background and Objectives: The tumoral biomarkers have a rather well known effect upon the tumor control period of several types of malignant lesions. The aim of this study was to evaluate the impact of immunohistochemical (IHC) markers of Ki-67 and p53 on the long-term outcome of growth hormone (GH)-secreting pituitary adenomas treated surgically. Materials and Methods: We conducted and followed a cohort of 47 consecutive patients with GH-secreting pituitary adenomas referred to our department during a 4 year period for trans-sphenoidal microsurgical adenomectomy. The expression levels of Ki-67 and p53 were determined by IHC study of the tissue samples. Periodical pituitary magnetic resonance imaging (MRI), visual field studies and hormonal evaluations (GH and insulin-like growth factor-1 [IGF-1]) performed during the follow-up period were the outcome measures. Results: The level of Ki-67 expression was higher among patients with postoperative residual tumor (3.5 vs. 1.7%) and those with a hormonal recurrence (4.3 vs. 1.6%). The p53 expression level was remarkably higher in patients with radiological recurrence (18 vs. 6.3%). Patients with invasive features (i.e. cavernous sinus and suprasellar invasion) had significantly higher p53 and Ki-67 values and higher IGF-1 levels during the follow-up period. The patients younger than 30 years of age and those with mixed GH-prolactin secreting adenomas had significantly higher hormonal remission and lower radiological recurrence rates. Conclusion: Each of the biomarkers, Ki-67 and p53, along with patient′s age and mixed GH-prolactin secretion showed a kind of correlation with each of aspects of the clinical, hormonal and radiologic outcome of GH-secreting pituitary adenomas in this series.