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.

A Nomogram for Preoperatively Predicting the Ki-67 Index of a Pituitary Tumor: A Retrospective Cohort Study

“…However, another study (50) reported an inverse relationship between the Ki-67 index and Knosp grade for functional PA and nonfunctional PA (R= -0.59, p < 0.001 in functional PA and R = 0.367, p < 0.01 in nonfunctional PA). Das et al found no significant correlation between Knosp grade and Ki-67 index (5). In the current research, PAs with the Knosp grades 0-2 and grades 3-4 were classified into noninvasive and invasive classes.…”

“…PA is the most common tumor in the sellar region (1), and high Ki-67 suggests invasive growth and worse prognosis for patients with PAs (2,5). Preoperative prediction of Ki-67 could further assist neurosurgeons to develop better, more individualized treatment strategies for patients with PAs.…”

“…The Ki-67 labeling index is a proliferative marker for PAs (3,4). A Ki-67 ≥3% is an indicator for invasive growth according to the World Health Organization 2004 classification (5). The French five-tiered classification is another approach for classifying PAs with validated prognostic value, and Ki-67 is used as one of the proliferative markers (2).…”

Prediction of Higher Ki-67 Index in Pituitary Adenomas by Pre- and Intra-Operative Clinical Characteristics

“…In a previous study, although the PAs were benign, some neoplasms still demonstrated invasive or aggressive growth, and tumor recurrence was observed during the postoperative follow up [ 11 ]. The Ki-67 index is considered a biomarker of aggressive tumor behavior, which is related to the invasiveness, aggressiveness, and recurrence of PAs [ 12 ]. Series studies have shown that a higher Ki-67 index is associated with a higher cell proliferation rate and more aggressive behavior in PAs [ 13 ].…”

A Preoperative MRI-Based Radiomics-Clinicopathological Classifier to Predict the Recurrence of Pituitary Macroadenoma Within 5 Years

“…The tendency to relapse has been related to many factors, including different histotypes, tumor remnants, or the extent of invasion into adjacent anatomical structures (6). Previous research has demonstrated that many clinicopathological prognostic tools have potential to predict the recurrence of PMA, consisting of IHC characteristics, invasion of tumors, genetic expression, and markers of proliferation (7)(8)(9)(10)(11). However, very few attempts have been made to integrate these risk factors with a machinelearning approach.…”