Low 06-Methylguanine-DNA Methytransferase (MGMT) and Pan-Cytokeratin (PAN-CK) Expression via Immunohistochemistry in Pituitary Adenomas

Abstract

Introduction. Pituitary adenomas (PA) are the third most common intracranial tumors, with an incidence rate of 10-15%. More than half are invasive, infiltrating adjacent structures. The primary objective of this project was to determine whether MGMT expression is associated with the invasiveness of PA. Material and Method. All patients who underwent surgical decompression consecutively between 2007-2012 were included. All data were obtained from the case records. Formalin-fixed paraffin-embedded (FFPE) tissue specimens were stained with hematoxylin and eosin (HE) and then examined via light microscope. Paraffin blocks that lacked necrosis and hemorrhage were chosen for histologic examination. In addition to an immunoprofile battery that consisted of Ki-67 and p53, MGMT, S-100 and Pan-CK were evaluated as well. Results. The subjects included 25 women and 15 men. The mean age was 48.9 ± 14.5 years. Of these, 63% of cases involved the invasion of adjacent structures. Of the PA, 17 (42%) were non-functioning pituitary adenomas (NFPA). There was a statistically significant relationship between the invasiveness and Ki-67, p53, MGMT expression, and prolactinoma. Gonodotropinomas were mostly non-invasive. FPAs presented invasive features more frequently than NFPAs. Pan-CK was positive in GH-secreting adenomas but negative in FSH-and LH-secreting adenomas. Conclusion. Ki-67 and p53 in lower expression level can be used for evaluating invasiveness but not for recurrence. MGMT expression can be a useful IHC indicator for invasiveness. However, Pan-CK cannot be used for invasiveness or aggressiveness.

Treatment Strategies for Dopamine Agonist-Resistant and Aggressive Prolactinomas: A Comprehensive Analysis of the Literature

“…Therefore, positivity of p53 expression is associated with p53 mutations [9]. It was shown that non-invasive and invasive adenomas and pituitary carcinomas exerted expression of p53 in 0, 15.2, and 100 % of cases, respectively, which correlated with invasion in a recent study [7]. In addition, it was shown that non-functioning pituitary adenomas are non-reactive for p53, while functional pituitary adenomas express p53, and functioning adenomas have more aggressive features than nonfunctioning adenomas including immunoreactivity for p53, S100, prolactin and MGMT (methylguanine methyltransferase) [7].…”

“…It is recommended the term "aggressive" should not be used synonymously with "invasive" as aggressivity encompasses a broader biologically ominious behavior including drug resistance and occasionally atypical histology besides invasiveness [5]. In general, invasiveness is mostly a radiological and aggressiveness a clinical definition [7]. Invasive prolactinomas are tumors with proven invasion into adjacent structures, including cavernous and sphenoid sinuses and bony structures, which can be defined radiologically with preoperative MR investigations, during operation, or with histopathological demonstration of tumor spread to the bone, dura, or nasal mucosa [7].…”

“…In general, invasiveness is mostly a radiological and aggressiveness a clinical definition [7]. Invasive prolactinomas are tumors with proven invasion into adjacent structures, including cavernous and sphenoid sinuses and bony structures, which can be defined radiologically with preoperative MR investigations, during operation, or with histopathological demonstration of tumor spread to the bone, dura, or nasal mucosa [7]. A relatively recent study demonstrated that prolactinomas constitute most invasive pituitary tumors [7].…”

“…Invasive prolactinomas are tumors with proven invasion into adjacent structures, including cavernous and sphenoid sinuses and bony structures, which can be defined radiologically with preoperative MR investigations, during operation, or with histopathological demonstration of tumor spread to the bone, dura, or nasal mucosa [7]. A relatively recent study demonstrated that prolactinomas constitute most invasive pituitary tumors [7]. In our index case, which will be discussed below, extensive cavernous sinus, prepontine area and pontocerebellar edge invasion and encasement of internal carotid artery, CV, CVII, and CVIII nerves were detected.…”

“…According to World Health Organization's (WHO) recent criteria (2016), increased mitotic index, Ki67 labeling index greater than 3 % percent and robust p53 expression indicate the aggressivity of pituitary adenomas [8]. But it shall be also emphasized that there exist conflicting results between Ki67 indices with invasiveness of pituitary tumors [7]. The tumor suppressor TP53 gene encodes the transcription factor p53, which is a genomic "gate keeper" that initially blocks cell cycle and succeedingly induces DNA repair following genomic damage.…”