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Objective: This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with impacted third molars. Materials and Methods: A comprehensive search strategy was employed across major databases including MEDLINE/PubMed, EMBASE, and Web of Science, from the inception of the databases to March 2024. Keywords and Medical Subject Heading (MeSH) terms such as "dentigerous cysts", "odontogenic keratocysts", "immunohistochemistry", "Ki-67", and "p53" were used. The PRISMA 2020 guidelines were followed to ensure methodological rigor. Inclusion criteria encompassed studies on humans and animals providing definitive diagnoses or specific signs and symptoms related to DCs and OKCs, with results on protein expression derived from immunohistochemistry, immune antibody, proteomics, or protein expression methods. Results: Of the 159 studies initially identified, 138 met the inclusion criteria. Our analysis highlighted significantly higher expressions of Ki-67 (22.1% ± 4.7 vs. 10.5% ± 3.2, p < 0.001), p53 (15.3% ± 3.6 vs. 5.2% ± 1.9, p < 0.001), and Bcl-2 (18.4% ± 3.2 vs. 8.7% ± 2.4, p < 0.001) in OKCs compared to DCs, indicating a higher proliferative index, increased cellular stress, and enhanced anti-apoptotic mechanisms in OKCs. Additionally, PCNA levels were higher in OKCs (25.6% ± 4.5 vs. 12.3% ± 3.1, p < 0.001). Genetic mutations, particularly in the PTCH1 gene, were frequently observed in OKCs, underscoring their aggressive behavior and potential malignancy. Conclusions: The findings emphasize the significant role of immunohistochemical markers in distinguishing between DCs and OKCs, with elevated levels of Ki-67, p53, Bcl-2, and PCNA in OKCs suggesting a higher potential for growth and recurrence. Genetic insights, including PTCH1 mutations, further support the need for personalized treatment approaches. These markers enhance diagnostic accuracy and inform targeted therapeutic strategies, potentially transforming patient management in oral and maxillofacial surgery. [ABSTRACT FROM AUTHOR]

Background: Condylar hyperplasia (CH) is a rare condition characterised by excessive unilateral growth of the mandibular condyle after cessation of growth on the contralateral side causing facial asymmetry, being more prevalent in the second and third decades. Objective: The aim of this study was to determine the utility of vascular endothelial growth factor (VEGF‐A) as a diagnostic and prognostic factor in condylar hyperplasia, and to determine its potential viability as a therapeutic target. Methods: This is a case–control study, where 17 mandibular condyles specimens were collected from 17 patients treated for active mandibular condyle hyperplasia and three unaffected human mandibular condyles from cadavers will serve as the control group. The samples were immunostained with VEGF‐A antibody and evaluated on both quantity and intensity of staining. Results: VEGF‐A was qualitatively found to be greatly upregulated in patients with condylar hyperplasia. Conclusion: VEGF‐A was qualitatively found to be upregulated in patients affected by CH, validating VEGF‐A as a potential diagnostic, prognostic and therapeutic target. [ABSTRACT FROM AUTHOR]

Temporomandibular disorders (TMD) are a group of internal derangements encompassing dysfunction, displacement, degeneration of the temporomandibular joints and surroundings muscles of mastication, often accompanied by pain. Relationships between TMD and various chemical biomarkers have been examined throughout the years. This paper aims to gather evidence from the literature regarding other biomarkers and presenting them as one systematic review to investigate the potential links between TMD and different biochemical activity. To identify relevant papers, a comprehensive literature search was carried out in MEDLINE/PubMED, EMBASE, Web of Science and a manual search was performed in the International Journal of Oral and Maxillofacial Surgery, Journal of Oral and Maxillofacial surgery, and Journal of Cranio-Maxillo-Facial Surgery. The literature review produced extensive results relating to the biochemical and immunohistochemical markers of TMD. Many enzymes, inflammatory markers, proteoglycans, and hormones were identified and organized in tables, along with a brief description, study design, and conclusion of each study. Through this review, recurring evidence provides confidence in suggesting involvement of certain biomarkers that may be involved in this complex pathogenesis, in addition to pointing to differences in gender prevalence of TMD. However, more organized research on large human samples needs to be conducted to delve deeper into the understanding of how this disease develops and progresses. [ABSTRACT FROM AUTHOR]

Objective: MMP-13 performs digestion of collagen, which is a primary component of the temporomandibular joint (TMJ) articular disc. This study evaluated the expression of MMP-13 in patients with anterior disc displacement with (ADDwR) and without reduction (ADDwoR), and in the presence of TMJ osteoarthrosis.Methods: Thirty-nine human temporomandibular joint disc samples were collected and divided in two ways: ADDwR (21 samples), ADDwoR (10 samples), and a control group (8 samples); and with osteoarthrosis (10 samples) and without osteoarthrosis (29 samples). Immunostaining of the TMJ discs was statistically compared between the groups.Results: There was no statistically significant difference for the area of MMP-13 immunostaining between the control group, ADDwR, and ADDwoR, nor between groups with and without osteoarthrosis.Conclusion: This study suggests MMP-13 is not significantly involved in collagen degradation in human TMJ disc displacement or osteoarthrosis. [ABSTRACT FROM AUTHOR]

Purpose: Interleukin-1 beta (IL-1β) is a cytokine that participates in the regulation of immune responses and inflammatory reactions. It is hypothesized that IL-1 levels may be elevated in patients suffering from temporomandibular joint dysfunction. The purpose of this study was to determine the association of IL-1β expression with TMD using an immunohistochemical approach to evaluate the joint disc.Materials and Methods: A total of 39 human temporomandibular joint disc samples were collected, with 31 samples in the test group. Nineteen of the test group samples were from discs of patients with anterior disc displacement with reduction, and 12 of the samples were from patients with anterior disc displacement without reduction. Eight control samples were used in the control group. The samples were immunostained and evaluated on both quantity and intensity of staining.Results: There was a statistically significant difference (p < 0.05) between the control and test groups for both quantity and intensity of staining.Conclusion: IL-1β plays a role in the inflammatory process and degradation of TMJ discs in patients with TMJ dysfunctions. [ABSTRACT FROM AUTHOR]

Temporomandibular joint (TMJ) internal derangement (ID) is one of the most common form of temporomandibular disorders. There is evidence showing the increased expression of matrix metalloproteinases (MMPs) in the cells from degenerated TMJ disc. ADAMTS are a large family of metalloproteases which are responsible for proteoglycans degradation. The present study aimed to evaluate ADAMTS-4 and ADAMTS-5 immunohistochemical expression in human TMJ discs from patients affected by ID, and to find out if there is any correlation with the degree of histopathological changes. Eighteen temporomandibular displaced disc specimens and sixteen TMJ disc control were used for the present study. Specimens were immunohistochemically processed and ADAMTS-4 and ADAMTS-5 expression were obtained respectively for the anterior (AB), intermediate (IB) and posterior (PB) bands and compared to the histopathological degeneration score (HDS). Immunoreactivity for ADAMTS-4 and -5, was observed in both not degenerated and degenerated human TMJ discs. Both the percentage of ADAMTS-4 and -5 immunostained cells (ES) and the intensity of staining (IS) were significantly greater in affected specimens compared with those in control discs. The ADAMTS-5 ES and IS of the 3 bands of the disc correlated to the TMJ disc HDS (0.001 < P < 0.05), on the other hand only AB and IB, ADAMTS-4 immunostaining scores correlated to HDS. According to these findings it can be assumed in that the more histopathological changes in the disc are detected, the higher levels of ADAMTS are produced. This in turn can lead to ECM breakdown and in turn to a more advanced disc displacement. [ABSTRACT FROM AUTHOR]

Purpose Matrix metalloproteases ( MMPs) are tissue-remodeling enzymes that function during the remodeling process, such as in immune-inflammatory diseases. Metalloprotease-2 ( MMP-2) and metalloprotease-9 ( MMP-9) are gelatinases that degrade several types of extracellular matrix collagen. It is hypothesized that in temporomandibular joint ( TMJ) dysfunction, MMP-2 and MMP-9 expression levels may be elevated. Therefore, the objective of this study is to determine the association of MMP-2 and MMP-9 expression with temporomandibular joint dysfunction using an immunohistochemical approach to evaluate the joint disk. Material and Methods A total of 45 human temporomandibular joint samples were collected, with 36 samples in the test group (patients with anterior disk displacement with reduction ( n = 29) and without reduction ( n = 7)) and nine samples in the control group. The immunostaining of the TMJ disks was statistically compared between the groups ( P < 0.05). Results There was a statistically significant difference for the area of MMP-2 immunostaining between the control group and the displacement disks with reduction group ( ADDwR) ( P = 0.048) and between the groups with disk displacement and without reduction ( ADDwoR) ( P = 0.029). The expression of MMP-2 was significantly elevated in the ADDwoR group. Conclusion No statistically significant difference was found between the variable area of MMP-9 expression in the disk with and without disk displacement, as determined by immunohistochemical analysis. However, there was an elevation of MMP-2 expression in the disks of patients with displacement and without reduction (more severe alteration). [ABSTRACT FROM AUTHOR]

Background Apoptosis is a programme of cell death which does not induce an inflammatory response. Recent previous research has suggested a correlation between temporomandibular internal derangement and apoptosis. Fas ligand (Fas L) is an apoptosis-inducing factor, known to trigger apoptosis through distinct signal pathways. This study aims to examine, by immunohistochemistry, the expression of Fas L in temporomandibular joint ( TMJ) articular discs of patients with anterior disc displacement with reduction ( ADDwR) and without reduction ( ADDwoR) in patients with and without osteoarthrosis ( OA). Methods Forty-two ( n = 42) TMJ articular discs were divided into two cut-offs: (i) 8 control, 17 ADDwR, 17 ADDwoR, and (ii) without OA ( n = 25) and with OA ( n = 17). The area of immunostaining was compared statistically between groups ( P < 0.05). Results Statistically significant differences were found in the expression of Fas L in TMJ discs between the three groups ( P = 0.001). ADDw R presented significant higher Fas L expression when compared with ADDwo R ( P < 0.001). Significant higher Fas L expression was observed in the group without OA ( P = 0.001). All patients without OA presented ADDw R, while all the patients with OA presented ADDwo R. Conclusion A higher area of in situ immunostaining of Fas L was found in temporomandibular discs with reduction, which is the less severe condition. Moreover, a reduced expression of Fas L in the discs of patients with osteoarthrosis was found, suggesting that some aspects of apoptosis might underlie the progression of TMJ disorders. [ABSTRACT FROM AUTHOR]

Objective. Two main apoptosis pathways have been identified: an extrinsic (or death receptor-mediated) and an intrinsic (or mitochondrial) pathway. Apoptotic cell death through the extrinsic pathway has just been described in temporomandibular joint disc (TMJ) with internal derangement (ID); in contrast, no data are available on the involvement of the intrinsic pathway in this tissue. The aim of this work was to investigate whether the intrinsic pathway participates in apoptosis activation in patients with TMJ ID and anterior disc displacement without reduction. Materials and methods. Apoptosis activation was studied in TMJ discs from 15 patients with ID and in six unaffected discs using bcl-2-associated X protein (bax), B-cell lymphoma 2 (bcl-2), cytochrome c and caspase 9 immunohistochemistry. A correlation was sought between immunohistochemical findings and degree of disc damage. Results. None of the pathological TMJ disc sections were immunopositive for bcl-2; negative bcl-2 immunostaining was detected in affected discs; cytochrome c and caspase 9 immunoreactivity was greater in pathological compared to unaffected discs; the difference was significant and correlated with histopathological degeneration score data (Spearman's rho = 0.617). Conclusion. The present findings suggest that in-human TMJ with ID and anterior disc displacement without reduction of cell apoptosis occurs, at least partly, via the mitochondrial pathway, which contributes to the subsequent disc degeneration. These data may have clinical implications and could help devise improved treatment strategies. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2012) 41: 642-647 Background: Internal derangement is the most frequent arthropathy affecting the temporomandibular joint, where its commonest form is anterior disc displacement with or without reduction. Despite the frequency of the disorder, the biochemical features of displaced discs are still unclear. Methods: We investigated the expression pattern and localization of aquaporin-1, an important channel protein involved in plasma membrane water permeability, in patients with anterior disc displacement (both with and without reduction), with a view to assessing the characteristics of local tissue responses to the microenvironmental changes induced by abnormal mechanical loading of the displaced disc. Protein expression was studied by immunohistochemistry in different areas of discs from 18 patients with anterior disc displacement with or without reduction and in four normal controls. Results: A greater proportion of cells immunopositive for aquaporin-1 were detected in diseased than in normal discs. Whereas protein expression was substantially similar in the different areas of normal discs, a significantly larger number of immunopositive cells were detected in the posterior band of displaced discs without reduction and in the anterior and intermediate bands of those with reduction. Conclusions: These findings suggest that aquaporin-1 is expressed and upregulated in temporomandibular joint with anterior disc displacement (both with and without reduction). [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2011) 40: 587–592 Lubricin is a chondroprotective, mucinous glycoprotein which contribute to joint lubrication, especially to boundary lubrication and maintains joint integrity. The present investigation aimed to study the immunolocalization of lubricin in TMJ discs from patients affected by anterior disc displacement with reduction (ADDwR) ADDwoR. Eighteen TMJ displaced disc affected by ADDwoR were processed immunohistochemically, with a polyclonal anti‐lubricin antibody, used at 1:50 working dilution. The percentage of lubricin immunopositive cells (extent score = ES) and the extent of lubricin staining of the disc extracellular matrix (ECM), were evaluated. Each sample was scored for histopathological changes. Percentage of immunostained surface disc cells was the same (ES = 4) in both control and ADDwOR cells, being this data not statistically significant (P < 0.05). In pathological specimens the percentages of lubricin‐stained cells was very high with an ES of 4 respect to control specimen, and this difference was statistically significant different (P > 0.05). The extracellular matrix (ECM) of discs at the disc surfaces of both pathological and normal specimens was very heavily stained (++++). Both the ES and ECM staining were not statistically correlated to the TMJ degeneration score according to the Spearman's rank correlation coefficient. According to our findings, a longstanding TMJ disc injury, affects lubricin expression in the TMJ disc tissue and not its surfaces, moreover, lubricin immunostaining is not correlated to TMJ disc histopathological changes. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2011) : 103-110 Internal derangement (ID) of the temporomandibular joint (TMJ) is due to an abnormal relationship of the articular disc to the mandibular condyle, glenoid fossa and articular eminence. The two most common types of internal derangement are anterior disc displacement with (ADDwR) and without reduction (ADDwoR). Disc displacement is associated with degenerative tissue changes. The histological features of discs from patients with TMJ ID reflect a general remodelling caused by abnormal loading. A correlation has been demonstrated between TMJ ID and apoptosis. Few investigations have addressed the role of apoptosis or caspase activity in TMJ ID. The apoptosis activation process was studied in different areas of discs from 18 patients with ID (both ADDwR and ADDwoR) and four cadavers (controls), with emphasis on the expression of caspase 3, whose activation makes the death process irreversible. The results showed a greater proportion of caspase 3-positive cells in ADDwR and ADDwoR than in control discs. Immunopositivity also varied between disc areas; in particular, in ADDwoR sections labelled cells were significantly more numerous ( P < 0.01) in the posterior disc attachment than in the anterior and intermediate bands. In addition, a significantly greater proportion of labelled cells was seen in the anterior (+) and intermediate (++) band of ADDwR compared with ADDwoR discs both bands ( P < 0.05). These data suggest the importance of programmed cell death in the progression of TMJ ID. [ABSTRACT FROM AUTHOR]