Evaluation of prognostic utility of Ki-67, P53, and O-6-methylguanine-DNA methyltransferase expression in pituitary tumors.

Abstract

BACKGROUND OR CONTEXT:Pituitary adenoma (PA) is the most common pathology of the pituitary gland. Pituitary tumors were historically considered benign, however, from recent advances in pathological and molecular analyses, numerous prognostic markers have been identified, allowing a better characterization of tumor behavior and prediction of response to treatment and recurrences.AIMS AND OBJECTIVES:Evaluation of the epidemiological occurrence of pituitary tumors in our center and prediction of the benign, aggressive, or malignant nature of the tumor with the help of immunohistochemical markers (IHC) Ki-67, P53, and O-6-methylguanine-DNA methyltransferase (MGMT) along with radiology.MATERIALS AND METHODS:A prospective study was done in 33 cases. Patients with clinically suspected pituitary tumors and related symptoms and signs are referred from the endocrine outpatient department and subsequently operated at the neurosurgery department were selected. We have studied the clinical features, radiology, histopathology, and IHC with the help of Ki-67, P53, and MGMT of PA over 2 years.RESULTS:We have 94% (31/33) cases of PA among them 94% (29/31) cases are macroadenoma. The IHC was conducted on 30 cases (excluding 1 case of pituitary apoplexy) where Ki-67, p53, and MGMT have been used for IHC in order to analyze the prognosis of the PA, irrespective of the immunological subtype of the PA. In our study, only 13% (4 patients) had MGMT score 0 and 2 patients, among these 4 patients having above cutoff level of Ki-67 and p53 value, considered as aggressive (in case of Ki-67 >3% and >50% in case of p53). When comparing MGMT expression with recurrence, a high degree of significance was found (Mann–Whitney U-test, P = 0.0038). Most of the recurrent tumors (6/9) had MGMT score 1 or below and most of the nonrecurring tumor had MGMT score 2 or above. When comparing MGMT expression with aggressiveness, a high degree of significance was found (Mann–Whitney U-test, P < 0.0001). Finally, combining the radiological Ki-67, p53, and MGMT values, two cases of aggressive adenoma have been seen in our study, the remaining being benign adenomas (WHO classification 2004). We did not encounter any case of pituitary carcinoma. MGMT did not show any significant correlation with radiological grading and histology.CONCLUSION:The benign, aggressive, or malignant nature of PA can be effectively predicted with the help of IHC, such as Ki-67, p53, and MGMT. This helps in better patient management and predicts recurrences and prognosis.