Association of Cortactin and MDM2 in Solid Ameloblastoma and its Malignant Counterpart

Abstract

Ameloblastoma is characterized by heterogeneity regarding its pathogenetic development, molecular abnormalities, and clinical course. Determining the molecular basis underlying these important differences remains challenging. Nevertheless, identifying molecules that influence tumor behavior would be the first steps towards gaining some insights into its pathobiology. MDM2, a 90-95kDa protein coded by a mdm2 gene which is mapped on chromosome 12q13-14. MDM2 is a negative regulator of p53 activity, through binding to the transcriptional activation domain of p53 leading to proteasome-mediated degradation, Cortactin, a product of CTTN gene, mapped to human chromosome 11q13 regulates actin-related (Arp2/3) complex induction of actin polymerization during invadopodia formation, thereby promoting cell motility. This has been accomplished through its involvement in all steps of the invadosome lifecycle, from the assembly, maturation, proteolytic activity, and disassembly. This study aims to evaluate the association of both MDM2 and Cortactin expression in solid ameloblastoma and its malignant counterpart and analyzing their significance. 10 cases of SAB with its different histologic variants and 20 cases malignant variants of ameloblastoma tumors were collected. An immunohistochemical investigation using, Cortactin, and MDM2 antibodies were done for all specimens. There was a statistically significant difference between malignant group and benign group. According to the current study Cortactin and MDM2 can be useful when considering the diagnosis of malignancy.

The controversial role of MDM2, MCM3 and Bcl-X in Ameloblastoma and Ameloblastic Carcinoma: An update

“…N.A., 2019 [19] concluded that MDM2 immunoreactivity was found predominantly in peripheral ameloblast like cells and it was also seen in central stellate reticulum like cells suggesting that peripheral cells essential and mean cell for evaluating the proliferative activity of AM. [18,19,21] As well Kumamoto et al ( 2004) [24] found that elevated expression of MDM2-p53, p14 in benign and malignant AM suggested that alteration of MDM2-p53, p14 cascade leads to oncogenesis or malignant transformation of odontogenic epithelium and is associated also with tissue structuring and cytodifferentiation of AM [24] .…”

“…Odontogenic tumors are a diverse group of osteo-destructive lesions with a wide range of clinical and biological characteristics. Diagnosis of odontogenic tumors can be challenging due to their rarity and diverse morphology [18][19][20] In view of this fact, a growing number of studies have tried to identify epithelial and mesenchymal factors that participate in the regulation of their growth and determine the differences in behavior between these diseases. The rarity of malignant odontogenic tumors, variations in their pathogenesis and biological behavior all contribute to the difficulty in diagnosing them.…”

“…Moreover, it may be difficult to distinguish some of these tumors from their benign counterparts and verifying their odontogenic origin can be challenging at times. The most obvious characteristics of malignant tumors are proliferation and migration [18][19][20] .…”

“…Determining the molecular basis for these significant disparities is still a challenge. Discovering proteins that regulate tumor behavior, would be the first step toward understanding its pathobiology [18] . Ameloblastic carcinoma (AC), the malignant counterpart of ameloblastoma, is a development of a previously benign AM.…”