P53 Suppressor Gene Tissue Microarray-based Protein Expression Analysis in Meningiomas

Abstract

Background/Aim: Meningiomas represent the main intracranial primary central nervous system (CNS) tumour in adults worldwide. Oncogenes' over-activation combined with suppressor genes' silencing affect negatively the biological behavior of these neoplasms. This study aimed to explore the impact of p53 suppressor gene expression in meningiomas' clinic-pathological features based on a combination of sophisticated techniques. Materials and Methods: Fifty (n=50) meningiomas were included in the study, comprising a broad spectrum of histopathological subtypes. An immunohistochemistry assay was applied on tissue microarray cores followed by digital image analysis. Results: p53 protein over-expression (high staining intensity levels) was observed in 27/50 (54%) cases, whereas the rest (23/50-/46%) demonstrated moderate to low levels of the protein. p53 over-expression was statistically significantly correlated to the mitotic index of the examined cases (p-value=0.001). Interestingly, the atypical/anaplastic group of histotypes demonstrated the strongest p53 expression rates compared to the others (p-value=0.001). Conclusion: p53 overexpression is observed in a broad spectrum of meningiomas. High expression levels lead to an aggressive biological behavior of the malignancy (combined with increased mitotic rates), especially in atypical and anaplastic sub-types that also have a high recurrence rate.Neoplastic formation and malignant transformation are based on a cataract of abnormal intra-and extra-cellular reactions inside the corresponding epithelia (1). Up-regulation of proliferation combined with apoptosis inhibition critically influences the carcinogenetic process (2). Among genes that significantly modify crucial cell functions, p53 is one of high importance (3). Concerning cell cycle, p53 acts as a key regulator, stabilizing the genome domain and regulating its function. The corresponding gene -located on chromosome's 17 (Chr 17) short (p) arm at position 13.1 (17p13.1) -encodes for a 53 kDa nuclear phosphoprotein. p53 protein acts as a strong transcription/suppressor factor controlling cell proliferation. It is also implicated in different cell-signaling pathways that regulate cell cycle phases, programmed cell death, and DNA replication/repair (4). MDM2, a protooncogene (12q14.3) that encodes for a nuclear-localized E3 ubiquitin ligase, controls p53 protein expression levels in a p53-MDM2 auto-regulatory pathway. In fact, MDM2 binds 2205