Expression of Pro-Apoptotic P53 Tumor Suppressor Gene in Pituitary Adenomas: Comparison with Anti-Apoptotic Bcl-2 Oncoprotein

Abstract

Background: While a great deal of attention has been paid to the study of the control of hormone secretion from Pituitary Adenomas (PAs), less attention has been paid to the study of molecular events that underlie the development of these tumors. Objectives: The goal of the present study was to analyze the expression of p53 tumor suppressor gene to allow for its comparison with that of oncoprotein bcl-2 in a series of PA patients followed for a minimum of nine years. Methods: This retrospective study included 51 patients diagnosed with a PA (33 nonfunctioning, 13 acromegaly, 4 Cushing’s disease, and one prolactinoma), who underwent trans-sphenoidal surgery at a single center between 2006 and 2008. P53 and bcl-2 expression were immunohistochemically evaluated and correlated with clinico-radiological and histopathological tumor parameters, as well as post-operative progression/recurrence. Results: Out of 51 tumors, 40 were categorized as typical and 11 as “atypical” PAs. From typical PAs, 28 showed positivity for p53 (cellular mean: 0.99%) and 20 for bcl-2 (cellular mean: 0.58%); from “atypical”, seven had p53 positive cells and six bcl-2 (mean: 2.02% and 0.73%, respectively). Nineteen (37.25%) were positive for the two markers. There were no differences in the expression of p53 and bcl-2 with regards to age or gender of the patient, size, invasiveness or post-operative tumor recurrence. Conclusions: In the study group, p53 and bcl-2 were abnormally expressed in 68.63% and 50.98% of pituitary tumors, respectively. One-third of PAs were co-expressed across both immunomarkers. The simultaneous genetic complementation of deregulated p53 and bcl-2 is implicated through the apoptosis regulation pathway in the pathogenesis of these tumors.