5.1 Ameloblastin

Ameloblastin (AMBN), also referred to as amelin or sheathlin, is a glycoprotein specific to teeth and is the most abundant enamel matrix protein aside from amelogenin. It is highly expressed during the secretory stage of enamel formation but decreases in expression during the maturation stage. While Ameloblastin is also found in dentin matrix and Hertwig's epithelial root sheath cells, its exact role in dentin and cementum formation has not been fully understood. Notably, AMBN is primarily located near the cell surface rather than deep within the enamel matrix layer [15].

Perdigao and colleagues research findings indicate that mutations in the AMBN gene are linked to the development of certain epithelial odontogenic tumours, including Ameloblastoma, Adenomatoid Odontogenic Tumour (AOT), Squamous Odontogenic Tumour (SOT), and Calcifying Epithelial Odontogenic Tumour (CEOT). Their findings suggest that mutations in the AMBN gene play a role in the tumorigenesis of these tumours, particularly those that arise from epithelial tissues without involvement of odontogenic ectomesenchyme, highlighting the genetic foundations of these specific types of tumors [16].

5.2 Amelogenin

Amelogenin is one of the key enamels—matrix proteins that plays a crucial role in the formation of dental enamel, which is the hard, outermost layer of teeth. It is primarily produced by secretory ameloblast cells during the secretory phase, which is essential for organizing and mineralizing developing enamel. The human amelogenin gene is found on both the X and Y chromosomes, specifically on Xp22.1–p22.3 and Yp11.2. Approximately 90% of amelogenin transcripts are produced from the X chromosome, while the remaining 10% originate from the Y chromosome [17].

Amelogenin diverse roles in enamel formation, genetics, forensics, and its potential applications in dental and regenerative medicine highlight its significance in various scientific and clinical fields as shown in Table 4.

Table 4 Key points about the role of Amelogenin

Mori and colleagues conducted a study where they found that amelogenin expression showed positive results in various types of lesions, including Ameloblastoma, Adenomatoid Odontogenic Tumor (AOT), Calcifying Epithelial Odontogenic Tumor (CEOT), Ameloblastic Fibroma (AF), Malignant Ameloblastoma, and Ameloblastic Carcinoma. Notably, the highest intensity of amelogenin expression was observed in the reduced ameloblasts within odontoma [18]. Consequently, the use of amelogenin as a marker proves to be a valuable tool for distinguishing and categorizing various types of epithelial lesions that may arise in the oral and maxillofacial regions. This marker aids in the differentiation of these lesions, enhancing the accuracy of diagnoses and facilitating appropriate clinical management [3, 19]. In a study by Kumamoto et al., samples of squamous cell carcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, and basal cell carcinoma did not exhibit expression of amelogenin [19]

5.3 Basement membrane proteins

Basement membrane proteins are a group of specialized proteins that play a crucial role in the formation and maintenance of the basement membrane, a thin, sheet-like structure that separates and supports epithelial and endothelial tissues from underlying connective tissues. Basement membrane proteins collectively provide structural support, facilitate cell adhesion and migration, regulate the passage of molecules, and contribute to various biological functions within tissues as shown in Table 5 [20].

Table 5 Key biological functions of basement membrane proteins

The study conducted by Poomsawat and colleagues revealed the expression of several basement membrane proteins, including laminins 1 and 5, collagen type IV, and fibronectin, in different types of odontogenic tumors such as ameloblastomas, and adenomatoid odontogenic tumors (AOTs). Interestingly, they found that laminin 1 expression was specifically observed in odontogenic epithelium but not in mucosal epithelium., highlighting the diagnostic significance of laminin 1 in characterizing and differentiating various odontogenic tumors and related oral lesions [21].

5.4 Bone morphogenic protein

Bone morphogenic proteins (BMPs) are a group of multifunctional growth factors belonging to a subset of the transforming growth factor-beta (TGF-β) superfamily of proteins that play pivotal roles in various biological processes, particularly in bone and cartilage formation, promote tissue regeneration and repair, and play roles in embryonic development as summarized in Table 6 [20]. Bone morphogenic proteins are critical regulators of tissue development and regeneration, making them essential players in both normal physiology and clinical medicine.

Table 6 Key roles of BMP in biological processes

In a study conducted by Gao YH and colleagues, it was observed that cementoblastoma, odontogenic fibroma, and odontoma exhibited positive expression of BMP. Conversely, ameloblastoma, adenomatoid odontogenic tumor (AOT), and calcifying epithelial odontogenic tumor (CEOT) did not express BMP. This suggests that BMP likely plays a significant role in the formation of calcified dental tissues and the development of odontogenic tumors that contain such tissues [23].

In the study conducted by Kumamoto and colleagues, they observed BMP expression in tooth germs and epithelial odontogenic tumors. This observation suggests that these regulatory proteins, which are involved in developmental processes, may have a role in influencing the cytodifferentiation of both normal and neoplastic odontogenic epithelium through interactions between epithelial and mesenchymal cells. In essence, BMPs may contribute to the processes that guide the development and differentiation of dental tissues, including those involved in odontogenic tumors [24].

5.5 Calretinin

Calretinin is a calcium-binding protein that plays important roles in various cellular processes, particularly in calcium signalling pathways within cells, which are crucial for various cellular processes, including neurotransmission and muscle contraction. In the nervous system, calretinin is commonly found in specific populations of neurons, including some interneurons in the central nervous system (CNS) and neurons in the peripheral nervous system (PNS). It is involved in modulating neuronal excitability and synaptic transmission [25]. It is also utilized as a valuable marker in some cancer types, including mesothelioma, where it can help differentiate between malignant and benign tissues [26].

In a study conducted by Alaeddini and colleagues, they observed that calretinin immunoreactivity was only positive in cases of ameloblastoma when compared to other odontogenic tumors such as calcifying epithelial odontogenic tumor, adenomatoid odontogenic tumor, ameloblastic fibroma, and odontogenic myxoma. They proposed that calretinin might be involved in the transition of dental lamina remnants into ameloblastoma, implying its potential relevance in the development and aggressive nature of this neoplasm. This observation highlights the potential significance of calretinin as a biomarker in distinguishing ameloblastoma from other similar lesions [27].

Chitra Anandani and colleagues suggested that calretinin could serve as a valuable immunohistochemical marker for identifying neoplastic ameloblastic epithelium. They observed that calretinin positivity was exclusively found in cases of ameloblastomas. Therefore, it can be utilized as an important diagnostic tool when distinguishing ameloblastomas from other dental lesions. The expression of calretinin in these neoplastic lesions may mirror the processes involved in normal tooth development, adding to its significance in ameloblastic tumors. Consequently, calretinin can be considered a specific immunohistochemical marker for neoplastic ameloblastic epithelium, demonstrating its presence exclusively in solid and unicystic ameloblastomas and not in any other types of odontogenic cysts or tumors. This highlights its diagnostic utility in the differential diagnosis of ameloblastomas [28].

5.6 Cytokeratin

Cytokeratins (CK) are a diverse group of intermediate filament proteins in epithelial cells, contributing to cell structure and function. Their tissue-specific expression and changes in expression patterns are valuable in diagnostics and cancer research. They also have emerging roles in cellular signalling and tissue repair processes. Cytokeratins are classified into two types: acidic and basic as shown in Table 7 [29]. They are numbered based on their molecular weight, with acidic cytokeratins having lower molecular weights and basic cytokeratins having higher molecular weights.

Table 7 Classification of cytokeratin

The expression of cytokeratins in odontogenic tumors as summarized in Table 8 can vary, and the presence of specific cytokeratins may aid in the diagnosis and classification of these tumors [30,31,32]. The expression patterns of cytokeratins can provide valuable information for pathologists and clinicians in understanding the nature of the tumor and distinguishing it from other lesions.

Table 8 Expression of cytokeratin’s in odontogenic tumors5.7 CD147

CD147, also known as Basigin (BSG) or EMMPRIN, M6 antigen, neurothelin (Extracellular Matrix Metalloproteinase-Inducer), is a type I transmembrane glycoprotein composed of two immunoglobulin-like domains (extracellular domain) and a short cytoplasmic tail and belongs to the immunoglobulin superfamily. It is primarily localized on the cell surface, where it functions as a receptor and cell adhesion molecule. It is widely distributed in various tissues and cell types, including leukocytes, red blood cells, endothelial cells, fibroblasts, and some epithelial cells. CD147 is well-known for its role in cancer progression. It promotes tumor invasion and metastasis by interacting with extracellular matrix proteins and facilitating the secretion of matrix metalloproteinases (MMPs), which degrade the extracellular matrix [33].

CD147 has been identified in ameloblastoma, or their precursor cells (dental lamina, remnants of dental lamina). Cairns et al. reported that CD147 expression was restricted to the cell membranes of columnar ameloblast-like cells and localized to the outer edges of epithelial cell clusters and the epithelial chords seen in Solid Multicystic Ameloblastoma. Its expression in ameloblastoma suggests a potential involvement in the local invasive behaviour of this tumor. CD147 may contribute to the breakdown of the extracellular matrix, facilitating tumor cell invasion into surrounding tissues [34]. CD147 has been implicated in the pathogenesis of various odontogenic tumors beyond ameloblastomas, including calcifying cystic odontogenic tumors and adenomatoid odontogenic tumors. Its role in these tumors may involve stimulating the production of matrix metalloproteinases (MMPs), which are associated with tumor invasiveness and aggressiveness [3].

5.8 Claudin

Claudins are a family of integral membrane proteins that play a crucial role in forming tight junctions between cells in various tissues. Tight junctions are specialized structures that seal the intercellular space between adjacent epithelial or endothelial cells, regulating the passage of ions, solutes, and macromolecules across cell layers [35].

The specific types of claudins recognized in odontogenic tumors can vary. The presence of these claudins in ameloblastoma, in particular, suggests their involvement in cell adhesion, tight junction formation, and potentially tumor behaviour as shown in Table 9 [36].

Table 9 Types of Claudins expressed in odontogenic tumors

Bello et al. noted a strong immunoreactivity of claudins 1, 4, and 7, particularly in stellate reticulum-like cells within ameloblastomas, suggesting their role in promoting cell–cell adhesion. Conversely, the expression of these claudins is typically weaker or moderate in ameloblastic carcinomas, possibly indicating a correlation with the aggressive behavior characteristic of these carcinomas. Abnormality in the permeability of tight junctions allows diffusion of the factors which has role in promoting tumor growth. Decreased expression of claudin is associated with dismantle of tight junction that can promote tumor invasion and has also been observed in oral squamous cell carcinoma [36]. Other odontogenic tumors, like adenomatoid odontogenic tumors (AOT), ameloblastic fibroma and ameloblastic carcinoma also exhibit expression of claudins.

5.9 High-mobility group A protein 2 (HMGA2)

High Mobility Group A Protein 2 (HMGA2) is a protein encoded by the HMGA2 gene in humans. It belongs to the high mobility group (HMG) protein family, which consists of non-histone chromosomal proteins involved in DNA binding, chromatin structure, and gene regulation, cell proliferation and tumorigenesis. Sato et al. proposed that alterations in the HMGA2 gene, such as rearrangements, and the increased expression of HMGA2 protein could potentially be linked to the development of odontogenic tumors, including odontogenic myxoma and odontogenic myxofibroma. Therefore, they suggest that these HMGA2 protein and gene characteristics are associated with odontogenic mesenchymal tumors [37].

5.10 Integrins

Integrins are a family of cell adhesion receptors that play a pivotal role in cell–cell and cell-extracellular matrix (ECM) interactions. These transmembrane proteins are crucial for various cellular processes, including cell adhesion, signalling, migration, and tissue organization.

As per the findings of Andrade ES et al., α5β1 integrin expression is notably higher in ameloblastomas compared to other odontogenic tumors such as AOT. This heightened expression implies a probable involvement of α5β1 integrin in the invasion mechanism of tumors. By binding to fibronectin, it potentially augments the secretion and presence of metalloproteinases, which are known to facilitate tumor invasion. Conversely, α3β1 integrin focal expression might induce disorganization of the basement membrane in certain areas of ameloblastomas, contributing to their invasive nature [38].

Increased expression of specific integrins, such as α5β1, indicates an enhanced interaction between tumor cells and the extracellular matrix (ECM). This upregulation may facilitate tumor invasiveness by strengthening cell adhesion, migration, and the release of matrix-degrading enzymes like metalloproteinases. Such elevation could signify a more aggressive tumor phenotype, predisposing to local invasion and metastasis. On the contrary, reduced levels of integrins observed in ameloblastomas, notably α3β1, might induce changes in cell—ECM interactions, resulting in impaired adhesion. This reduction could disturb the structural integrity of the basement membrane, potentially enabling tumor cells to detach and migrate towards adjacent tissues.

The absence of integrin α3β1 detection in tooth germs indicates its potential utility as a marker for neoplastic transformation in odontogenic tissues. Additionally, considering the heightened expression of integrins α2β1 and α5β1 in ameloblastomas, targeting these integrins may emerge as a significant therapeutic approach to manage or mitigate the local invasiveness of this tumor [38].

5.11 Matrix metalloproteinases

Matrix metalloproteinases (MMPs) are a family of enzymes that play a crucial role in tissue remodelling and degradation of the extracellular matrix (ECM). These enzymes are involved in various physiological processes like embryogenesis, angiogenesis, immune response and are also associated with several pathological conditions such as cancer, arthritis, atherosclerosis and neurological disorders.

MMPs particularly MMP-2 (gelatinase A) and MMP-9 (gelatinase B), are crucial in facilitating the invasion and metastasis of odontogenic tumors such as ameloblastoma and ameloblastic carcinoma, as they participate in breaking down the extracellular matrix (ECM). Their role in breaking down components of the extracellular matrix (ECM), such as collagen and gelatin, may facilitate tumor cell invasion. The presence and activity of various MMPs, including MMP-1, MMP-2, MMP-7, MMP-9, and MMP-26, within ameloblastomas (AB) showed significant correlations with several clinicopathologic features of these tumors. These characteristics encompassed aspects like the rate of growth, invasive behavior, and the potential for metastasis. This suggests that the expression of these MMPs may be associated with the aggressive behavior and clinical characteristics of ameloblastomas [39, 40]. Other odontogenic tumors, like odontogenic myxoma, adenomatoid odontogenic tumors (AOT), and ameloblastic fibroma, also exhibit expression of MMPs.

5.12 Nestin

Nestin is an intermediate filament protein that is commonly associated with stem cells, particularly neural stem cells, and is involved in various aspects of cellular processes, including cytoskeletal organization, cell division, and differentiation. It has been found in other tissues and organs, including muscle, pancreas, and blood vessels.

The expression of nestin in odontogenic tumors is associated with the ectomesenchymal tissue's origin from the neural crest. However, a study conducted by Fujita et al. revealed that nearly all cases of ameloblastomas and malignant ameloblastomas did not exhibit nestin expression. In contrast, in mixed tumors like ameloblastic fibroma (AF) and Ameloblastic fibro—sarcoma, the odontogenic ectomesenchyme displayed robust nestin expression, particularly in the vicinity of the neoplastic follicular odontogenic epithelium [41]. Hence, it can be inferred that nestin may serve as a valuable marker for tumors originating from odontogenic ectomesenchymal tissues.

5.13 Podoplanin

Podoplanin, also known as PDPN, is a transmembrane glycoprotein that plays important roles in lymphangiogenesis, cancer metastasis, platelet aggregation, and tissue regeneration. Podoplanin can also enhance cancer cell invasiveness and migration. As reported by Gonzalez-Alva et al., strong expression of podoplanin was observed in the peripheral columnar cells of ameloblastomas, with a relatively weaker expression noted in the central stellate reticulum-like cells of these tumors [42]. Ganvir et al. observed robust expression of Podoplanin at the invasive front, particularly in the peripheral odontogenic epithelial cells of the majority of tumors and dental follicles. In cases of ameloblastomas, the membranous expression of Podoplanin was more intense in instances displaying aggressive behavior compared to non-aggressive ameloblastomas. The presence of podoplanin at the invasive front, particularly in peripheral cells, of odontogenic tumors suggests its association with neoplastic odontogenic tissues. This molecule is believed to potentially contribute to the progression and local invasion of odontogenic tumors which may be linked to its ability to induce cytoskeletal reorganization within the cells [43].

5.14 SOX 2 and OCT 4

SOX2 (SRY-Box Transcription Factor 2) and OCT (Octamer-Binding Transcription Factor) are transcription factors that play crucial roles in the regulation of gene expression and cell differentiation, stem cell maintenance, pluripotency, and development. Both are highly expressed in embryonic stem cells, neural stem cells, germ cells and various adult stem cell populations. In the odontogenic tumors, stem cell populations within these tumors may express SOX2, potentially contributing to their growth and maintenance. SOX2, in collaboration with the transcription factors OCT4 (Octamer binding protein 4) and Nanog, plays a crucial role in maintaining the stemness properties of pluripotent stem cells, including their ability to self-renew and differentiate into various cell types. Furthermore, when expressed in unusual locations, SOX2, together with OCT4 and KLF4, can reprogram differentiated cells into induced pluripotent stem cells (iPSCs) [44].

5.15 Syndecan

Syndecans are a family of transmembrane heparan sulfate proteoglycans (HSPGs) that play essential roles in various cellular processes. These cell surface molecules are involved in cell–cell communication, adhesion, and signaling. Bologna-Molina et al. observed that solid ameloblastoma (SA) exhibited lower levels of syndecan-1 (SDC1) expression compared to unicystic ameloblastoma (UA). This reduced syndecan-1 expression in SA suggests that SA may exhibit a more aggressive biological behavior in comparison to UA [45]. Syndecan-1 appears to play a role in the development of ameloblastoma, ameloblastic fibroma (AF), and adenomatoid odontogenic tumor (AOT). According to the findings of Al-Otaibi et al., the presence of syndecan-1 (SD1) expression in stromal cells and the extracellular matrix (ECM) is an important factor contributing to the development of intra-osseous ameloblastomas and their ability to locally invade surrounding tissues [46].

Syndecans have been detected in various odontogenic tumors like ameloblastic carcinoma, adenomatoid odontogenic tumors (AOTs), and ameloblastic fibromas. Research indicates distinct syndecan expression patterns in these tumors compared to normal tissues, suggesting their probable role in tumor progression and development. Particularly, the expression of syndecan-1 (SDC1) varies among different odontogenic tumors, with some tumors showing reduced SDC1 levels. This variation in expression might mirror differences in tumor aggressiveness and behavior. Overall, syndecan expression in odontogenic tumors highlights its potential as a diagnostic marker and its involvement in tumor pathogenesis [46].

5.16 Tenascin

Tenascin is a family of extracellular matrix (ECM) glycoproteins that play significant roles in various biological processes, including tissue development, wound healing, and immune responses. There are four major members of the tenascin family: tenascin-C, tenascin-R, tenascin-X, and tenascin-W. Tenascins can influence cell behavior and tissue structure through their interactions with other ECM components, cell surface receptors, and signaling pathways. Nagai et al. conducted a study to investigate the expression of tenascin in different dental tissues, including ameloblastomas, ameloblastic fibromas, ameloblastic carcinomas, and tooth germs. Their findings revealed varying levels of tenascin expression: Ameloblastic fibromas showed high tenascin expression in both the basement membrane and stromal areas, Follicular ameloblastomas displayed tenascin positivity primarily in the basement membrane zone, displaying an uneven linear pattern and Ameloblastic carcinomas exhibited an irregular and robust response to tenascin in both stromal and basement membrane regions. To sum up, the presence of tenascin can indicate interactions between epithelial and mesenchymal components in tooth development, and its expression varies among different dental tissues. Additionally, it serves as a valuable marker for distinguishing odontogenic tumors such as CEOT & odontomas that form calcifying masses from those that do not [47].

5.17 Wingless type 1 glycoprotein (Wnt 1)

Wingless type 1 glycoprotein, often referred to as Wnt-1, is a member of the Wnt family of signaling proteins. Wnt proteins are secreted glycoproteins that play crucial roles in various developmental processes, including embryogenesis, tissue regeneration, odontogenesis, regulation of cell fate and aberrant Wnt signaling can promote tumor growth, invasion, and metastasis. According to the findings reported by Chuah et al., a significant majority of primary conventional ameloblastomas, specifically 76.9%, exhibited robust Wnt1 immunoreactivity. In contrast, a lower percentage, specifically 42.9%, of primary unicystic ameloblastomas demonstrated strong Wnt1 immunoreactivity. These differences in Wnt1 expression patterns suggest potential variations in the molecular characteristics and behavior of these two types of ameloblastomas [48]. As reported by Siar CH et al., changes in the expressions of Wnt signaling molecules, specifically Wnts 1, 2, 5a, and 10a, have been observed in ameloblastomas. Among these, Wnt 1 appears to be a critical signaling molecule that may play a central role in the tumorigenesis of ameloblastomas. These findings suggest that aberrations in the Wnt signaling pathway contribute to the development of ameloblastomas by impacting cell proliferation and influencing the oncogenesis and cytodifferentiation of odontogenic epithelium [49].

5.18 Ki—67

Ki-67 is a 319—385 KDa protein marker that is commonly used as a proliferation marker in various tumors, including odontogenic tumors and indicates the proliferation or growth fraction of cells within a tumor. Ki-67 is expressed during the active phases of the cell cycle (G1, S, G2, and mitosis) but is absent in the resting phase (G0). In the context of odontogenic tumors, Ki-67 expression can provide valuable information about the tumor’s growth potential and aggressiveness. High Ki-67 labelling index (percentage of positively stained cells) may suggest a more rapidly proliferating and potentially more aggressive tumor [50].

Carreón-Burciaga et al. showed that Ki-67 expression is elevated in ameloblastic carcinomas (AC) compared to ameloblastomas (AM). This heightened expression was found to be associated with the aggressiveness of AC tumors, including features such as invasion and the presence of metastatic neoplasms [51]. Although it is beneficial, this immunomarker does not provide a clear distinction between benign and malignant tumors.

5.19 Glypican

Glypican (GPCs) is a family of cell surface heparan sulfate proteoglycans (HSPGs) that play crucial roles in various cellular processes, including cell signaling, growth, and differentiation. These proteoglycans are anchored to the cell membrane by a glycosylphosphatidylinositol (GPI) anchor and consist of a core protein linked to heparan sulfate chains. The GPC (Glypican) gene family comprises six members (GPC1-6), and Glypican 3 is recognized for its interactions with various signaling pathways. These pathways encompass those integral to embryonic development, tissue morphogenesis, and the control of cell growth. Glypicans can influence signaling pathways such as Wnt, Hedgehog (Hh), and FGF, which are essential for normal development but can also be dysregulated in cancer such as hepatocellular carcinoma, malignant melanoma, neuroblastoma, and colon cancer [52, 53].

According to Mendes et al. and Chaturvedi et al., the studies concluded that GPC3 plays a role in odontogenic tumors by differentiating between aggressive—ameloblastomas & unicystic ameloblastoma and nonaggressive odontogenic tumors—AOT. The expression of molecules associated with the Sonic Hedgehog (SHH) signaling pathway, including SHH, PTC, smoothened, and GLI1, has been identified in various odontogenic tumors. This suggests that the SHH signaling pathway contributes to epithelial–mesenchymal interactions and cell proliferation in the growth of odontogenic tumors, as well as during tooth development [52, 53]. Bologna-Molina et al. revealed the existence of GPC-1, another member of the GPC family, in various types of ameloblastomas. However, they did not observe any distinctions between solid and unicystic cases [54].

The exact significance of glypicans in diagnosing or predicting the prognosis of odontogenic tumors remains unclear. However, studies propose that glypicans, specifically glypican-3, might participate in diverse cellular signaling pathways linked to tumor development and advancement. Elevated levels of GPC3 correlate with the aggressive clinical nature of odontogenic tumors and an increased likelihood of recurrence. Analyzing the expression patterns of glypicans in odontogenic tumors could potentially offer understanding into their biological characteristics and clinical implications. Therefore, this marker shows potential for assessing the prognosis of odontogenic tumors [52, 53].

5.20 PITX 2

PITX2 (Pituitary homeobox 2) is a gene that codes for a transcription factor belonging to the homeobox family. Its expression is regulated by the Wnt cell signaling pathway, and it plays a vital role in embryonic development, as well as in processes such as cell proliferation and migration. It is involved in the regulation of various developmental processes, including the development of the pituitary gland, eyes, and other facial structures. Pitx2, identified as the initial transcriptional marker for tooth development, governs the embryonic establishment and arrangement of epithelial signaling centres throughout incisor development [55]. During the process of odontogenesis, PITX2 exhibits selective expression in the initial stages of morphogenesis within the oral ectoderm and epithelial cells. Disruptions in PITX2 expression during embryonic development can result in developmental irregularities, including conditions like enamel hypoplasia and anodontia [56].

García-Muñoz and colleagues propose a hypothesis suggesting that PITX2 serves as a significant transcription factor in odontogenic tumors, particularly in Ameloblastic carcinoma (AC) and to a lesser extent in unicystic ameloblastoma (UA). In Ameloblastic Carcinoma and to a lesser extent in benign ameloblastomas, akin to its roles in pituitary or colorectal cancer, PITX2 could potentially function as an activator of downstream oncogenes in the course of tumor progression. This association may be linked to tumor behavior, including factors such as aggressiveness, recurrence, and metastasis [56].

5.21 Wilms tumor (WT—1) gene

WT1 (Wilms tumor 1) is a gene that encodes a transcription factor involved in normal kidney development and function. Mutations or dysregulation of the WT1 gene have been implicated in the development of Wilms tumor, a Pediatric kidney cancer.

In the research conducted by Mukhopadhyay et al., their conclusion emphasized that the upregulation or overexpression of WT-1 is linked to tumorigenesis, proliferation, and localized aggressiveness in Ameloblastoma. The study also demonstrated that WT-1, typically a cytoplasmic marker, exhibited positivity in both the nucleus and nucleolus across various cell types, particularly in ameloblast-like cells [57]. In research conducted by Bologna-Molina et al., it was observed that none of the tooth germs exhibited WT-1 expression, while over half of the Ameloblastoma tissue samples displayed an overexpression of WT-1. These results indicate a potential oncogenic role for WT-1 in these lesions [58]. Research in the field of odontogenic tumors is ongoing, and molecular markers like WT1 may be explored in the future to understand their potential involv