Management regulations for odontogenic keratocyst: a case report and review of the literature.

BACKGROUND: Reconstruction of the entire dentition with odontogenic keratocyst is a very challenging quandary. Most cases of odontogenic keratocyst are often reported to be benign, resulting in severe occlusal discrepancies with the maxillary and mandibular dentition. Dental radiographs occasionally reveal an uncommon, locally aggressive developing cyst termed as odontogenic keratocyst, which is typically located in the posterior jaw. When this cyst occurs in the anterior region, it is often misdiagnosed with other periapical lesions due to its lack of response to pulp vitality tests. CASE PRESENTATION: This clinical case scenario demarcates the endodontic management of a patient diagnosed with odontogenic keratocyst. A 37-year-old Indian male patient reported to the department with throbbing pain in the lower left posterior tooth requiring endodontic therapy. This patient also presented with odontogenic keratocyst in the anterior region of the jaw, for which he had undergone surgical rehabilitation. This case report highlights the clinical protocol for the endodontic therapy in patient diagnosed with ododntogenic keratocyst. Masticatory impairment was not visible after the follow-up period and the treatment outcome was successful. CONCLUSION: This case report details the presentation, characteristic radiographic findings, and endodontic management of a patient with an extremely rare condition of odontogenic keratocyst. The management involves multidisciplinary approach for the rehabilitation.

Recurrence of Glandular Odontogenic Cysts: A Systematic Review.

BACKGROUND: The glandular odontogenic cyst (GOC) is a benign developmental cyst of the jaws that is characterized by a high recurrence rate. METHODS: A systematic review is presented of reported cases, case series, and retrospective studies of recurrent cases of glandular odontogenic cysts, to determine the overall and detailed demographic features with documentation of the specific histologic features of the initial presentation of each cyst. Searches of detailed databases were carried out to identify articles published in the English language from 1988 to 2023. The variables were demographics, patient symptoms, cyst location, radiographic features, histopathological findings, type of treatment, and minimum eight months of follow-up. RESULTS: Eighteen cases were identified: with an equal gender presentation of 50% females and 50% males. The average age was 44.7. The mean size was 3.5 cm. The most common location was in the anterior mandible in 50% (n = 9) of cases, followed by the posterior mandible 27.8% (n = 5). Most patients were asymptomatic 55.6% (n = 10). The most common histologic features at first diagnosis were mucous cells in 88.9% (n = 16), variable thickness with 83.3% (n = 15), eosinophilic cuboidal cells 88.9% (n = 16), microcysts 83.3% (n = 15), and clear cells 77.8% (n = 14) cases. CONCLUSION: GOC has an aggressive behavior. Evidence was not conclusive to link any single or combination of histologic features to recurrence, and the strongest correlation for recurrence was the type of treatment. Since this is an uncommon cyst, more cases are needed. Follow-up should continue for at least five years, because recurrences were higher between years 3 and 5.

Assessment of MUC5AC and MUC2 Immunoexpression in Glandular Odontogenic Cysts, Dentigerous Cysts, and Mucoepidermoid Carcinomas.

Glandular odontogenic cysts (GOCs) and dentigerous cysts may show mucous metaplasia. Central mucoepidermoid carcinoma is very rare and mostly associated with dental cysts. It is hypothesized that odontogenic cysts showing mucus differentiation in their lining, have a propensity to transform into MEC. The present study is the first attempt to explore the relationship between odontogenic cysts [GOCs and dentigerous cysts with mucus metaplasia (DCMM)] and MEC by evaluating immunoexpression of MUC5AC and MUC2. Immunoexpression of MUC5AC and MUC2 was evaluated semiquantitatively in GOCs (20 cases), DCMMs (20 cases), and MECs (20 cases). The percentage of positive cells, intensity, and localization of immunoexpression were assessed for each marker in all cases. Of GOCs, DCMMs, and MECs cases, 85%, 70%, and 80%, respectively, were immunopositive for MUC5AC. Strong cytoplasmic immunoreactivity for MUC5AC was noted, particularly in mucous cells present diffusely within MECs. However, the immunoreactivity was limited to the epithelial lining of GOCs and DCMMs. Most of the MECs (60%) showed more than 25% positivity for MUC5AC, followed by GOCs, and the least in DMMCs. Mild cytoplasmic and nuclear positivity of MUC2 was noted only in epithelial lining cells of 70% GOCs and 45% DCMMs. Whereas, 55% of MECs displayed moderate to strong cytoplasmic and membranous immunopositivity for MUC2 exclusively within mucous cells. As MECs showed strong MUC5AC immunoreactivity in mucous cells, immunoexpression of MUC5AC in odontogenic cysts with mucus cells can possibly explain the pathogenesis of MEC from cysts. However, the variable expression of MUC2 did not give any strong evidence regarding its role as a marker.

In Silico Analysis of Genes Associated with the Pathogenesis of Odontogenic Keratocyst.

Odontogenic keratocyst (OK) is a benign intraosseous cystic lesion characterized by a parakeratinized stratified squamous epithelial lining with palisade basal cells. It represents 10-12% of odontogenic cysts. The changes in its classification as a tumor or cyst have increased interest in its pathogenesis. OBJECTIVE: Identify key genes in the pathogenesis of sporadic OK through in silico analysis. MATERIALS AND METHODS: The GSE38494 technical sheet on OK was analyzed using GEOR2. Their functional and canonical signaling pathways were enriched in the NIH-DAVID bioinformatic platform. The protein-protein interaction network was constructed by STRING and analyzed with Cytoscape-MCODE software v 3.8.2 (score > 4). Post-enrichment analysis was performed by Cytoscape-ClueGO. RESULTS: A total of 768 differentially expressed genes (DEG) with a fold change (FC) greater than 2 and 469 DEG with an FC less than 2 were identified. In the post-enrichment analysis of upregulated genes, significance was observed in criteria related to the organization of the extracellular matrix, collagen fibers, and endodermal differentiation, while the downregulated genes were related to defensive response mechanisms against viruses and interferon-gamma activation. CONCLUSIONS: Our in silico analysis showed a significant relationship with mechanisms of extracellular matrix organization, interferon-gamma activation, and response to viral infections, which must be validated through molecular assays.

[Three-dimensional radiographic features of calcifying odontogenic cyst and calcifying epithelial odontogenic tumor].

OBJECTIVE: To analyze the three-dimensional radiographic characteristics of calcifying odontogenic cyst and calcifying epithelial odontogenic tumor using spiral computed tomography (CT) and cone-beam computed tomography (CBCT). METHODS: Clinical records, histopathological reports, and CBCT or non-enhanced spiral CT images of 19 consecutive patients with calcifying odontogenic cyst (COC) and 16 consecutive patients with calcifying epithelial odontogenic tumor (CEOT) were retrospectively acquired, and radiographic features, including location, size, expansion, internal structure and calcification, were analyzed. RESULTS: Among the 19 COC cases (12 males and 7 females, with an average age of 27 years), 89.5% (17/19) of the lesions originated from the anterior and premolar areas, 100.0% of them exhibited cortex expansion, and 78.9% had discontinued cortex. Among the 16 CEOT cases (3 males and 13 females, with an average age of 36 years), 81.3% (13/16) of the lesions were in the premolar and molar areas, 56.3% of them exhibited cortex expansion, and 96.8% had discontinued cortex. According to the distribution of internal calcifications, these lesions were divided into: Ⅰ (non-calcification type): absence of calcification; Ⅱ (eccentric marginal type): multiple calcifications scattered along one side of the lesion; Ⅲ (diffused type): numerous calcifications diffusely distributed into the lesion; Ⅳ (plaque type): with a ≥ 5 mm calcified patch; Ⅴ (peri-coronal type): multiple calcifications clustered around impacted teeth. Calcifications were present in 73.7% of COC lesions, including 9 type Ⅱ, 3 type Ⅲ and 2 type Ⅳ lesions, and 42.8% of CEOT lesions had calcification images, including 2 type Ⅲ and 5 type Ⅴ lesions. Six COC lesions had odontoma-like images. Moreover, 8 of 9 type Ⅰ CEOTs were histologically Langerhans cell-rich subtype, which had a smaller size (with an average mesiodistal diameter of 17.8 mm) and were not associated with impacted teeth. CONCLUSION: COC lesions tended to originate from the anterior part of the jaw and exhibit cortex expansion, and were sometimes associated with odontoma. CEOT commonly occurred in the posterior jaw and had discontinued cortex. Two lesions had significantly different calcification map. Over 70% of COC lesions had calcification images, which were mostly scattered along one side of the cysts, far from the impacted teeth. Approximately 60% of CEOT lesions exhibited smaller size and non-calcification, and the remaining CEOT cases often had calcification images clustered around the impacted teeth.

Immunohistochemical expression of SPARC in odontogenic keratocysts: a comparative study with other odontogenic cysts.

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) has been shown to modulate aggressive behavior in several benign and malignant tumors. Little is known about SPARC expression in odontogenic keratocyst (OKC), an odontogenic cyst with an aggressive nature. To the best of our knowledge, only one study has been investigated the expression of this protein in OKCs. This study aimed to characterize SPARC expression in OKCs. Additionally, to determine whether SPARC is associated with aggressive behavior in OKCs, SPARC expression in OKCs was compared with radicular cysts (RCs), dentigerous cysts (DCs) and calcifying odontogenic cysts (COCs). These odontogenic cysts showed no or less aggressive behavior. METHODS: SPARC expression was evaluated in 38 OKCs, 39 RCs, 35 DCs and 14 COCs using immunohistochemistry. The percentages of positive cells and the intensities of immunostaining in the epithelial lining and the cystic wall were evaluated and scored. RESULTS: Generally, OKCs showed similar staining patterns to RCs, DCs and COCs. In the epithelial lining, SPARC was not detected, except for ghost cells in all COCs. In the cystic wall, the majority of positive cells were fibroblasts. Compared between 4 groups of odontogenic cysts, SPARC expression in OKCs was significantly higher than those of RCs (P < 0.001), DCs (P < 0.001) and COCs (P = 0.001). CONCLUSIONS: A significant increase of SPARC expression in OKCs compared with RCs, DCs and COCs suggests that SPARC may play a role in the aggressive behavior of OKCs.

The IL-1ß-p65 axis stimulates quiescent odontogenic epithelial cell rests via TGF-ß signalling to promote cell proliferation of the lining epithelia in radicular cysts: A laboratory investigation.

AIM: Cyst formation of the jaws is frequently accompanied by the proliferation of odontogenic epithelial cells located in the periodontal ligament (PDL), which consists of heterozygous cells and includes the most fibroblasts. The lining epithelium of radicular cyst, an odontogenic cyst of inflammatory origin, is derived from the proliferation of the remnants of the Hertwig epithelial root sheath (odontogenic epithelial cell rests of Malassez; ERMs) in the PDL. ERMs are maintained at a lower proliferative state under physiological conditions, but the regulatory mechanisms underlying the inflammation-dependent enhanced-proliferative capabilities of ERMs are not fully understood. The aim of this study was to evaluate the effects of cytokine pathway association between TGF-ß signalling and IL-1ß signalling on the regulation of odontogenic epithelial cell proliferation using radicular cyst pathological specimens and odontogenic epithelial cell lines. METHODOLOGY: Immunofluorescence analyses were performed to clarify the expression levels of Smad2/3 and Ki-67 in ERMs of 8-week-old mouse molar specimens. In radicular cyst (n = 52) and dentigerous cysts (n = 6) specimens from human patients, the expression of p65 (a main subunit of NF-κB), Smad2/3 and Ki-67 were investigated using immunohistochemical analyses. Odontogenic epithelial cells and PDL fibroblastic cells were co-cultured with or without an inhibitor or siRNAs. Odontogenic epithelial cells were cultured with or without TGF-ß1 and IL-1ß. The proliferative capabilities and Smad2 phosphorylation levels of odontogenic epithelial cells were examined. RESULTS: Immunohistochemically, Smad2/3-positivity was increased, and p65-positivity and Ki-67-positivity were decreased both in ERMs and in the epithelial cells in dentigerous cysts, a non-inflammatory developmental cyst. In contrast, p65-positive cells, along with the expression of Ki-67, were increased and Smad2/3-positive cells were decreased in the lining epithelia of radicular cysts. Co-culture experiments with odontogenic epithelial cells and PDL fibroblastic cells revealed that PDL cells-derived TGF-ß1/2 and their downstream signalling suppressed odontogenic epithelial cell proliferation. Moreover, TGF-ß1 stimulation induced Smad2 phosphorylation and suppressed odontogenic epithelial cell proliferation, while IL-1ß stimulation reversed these phenotypes through p65 transactivation. CONCLUSIONS: These results suggest that IL-1ß-p65 signalling promotes odontogenic epithelial cell proliferation through suppressing TGF-ß-Smad2 signalling, which would be involved in the pathogenesis of radicular cysts.

Utility of BRAF V600E immunohistochemistry in the diagnosis of mandibular ameloblastomas.

Ameloblastoma, odontogenic keratocyst (OKC), and dentigerous cyst (DC) can have similar radiographic and histological appearances. The purpose of this study was to determine the utility of BRAF immunohistochemistry in discerning mandibular ameloblastomas from OKCs and DCs. This retrospective cohort study included patients treated between 1998 and 2018. Inclusion criteria include incisional biopsy-proven mandibular ameloblastoma, OKC, or DC, and sufficient tissue for immunohistochemistry. The primary predictor variable was the type of lesion. The primary outcome variable was the presence/absence of BRAF V600E immunoreactivity. The cohort consisted of 43 patients (19 female, 24 male; mean age 48 ± 17 years). There were 22 ameloblastomas, 11 OKCs, and 10 DCs. Among ameloblastomas, 68.2% (15/22) stained positive for BRAF V600E; no OKC or DC was positive (P < 0.001). By subtype, the majority of the follicular (83.3%), unicystic (83.3%), desmoplastic (66.7%), and acanthomatous (100%) subtypes were positive, but only 33.3% of the plexiform subtype were positive. BRAF immunohistochemistry may be a useful adjunct in the differentiation of ameloblastoma from OKCs and DCs on incisional biopsies. It may be particularly useful for small samples with a prominent cystic component or equivocal histopathology. Mandibular lesions that are BRAF immunohistochemistry positive are unlikely to be DCs or OKCs.

Mandibular primary intraosseous carcinoma arising from long-standing odontogenic keratocyst.

Primary intraosseous carcinoma (PIOC) of the jaw is a rare neoplasm arising from the lining epithelium of odontogenic cysts or de novo from odontogenic epithelial rests that has no communication with the surrounding mucosa of the upper aerodigestive tract. We present a case of PIOC ex-odontogenic keratocyst (PIOC ex-OKC) in a 35-year-old male. Histopathologic examination revealed a cystic lesion with a fibrous capsule lined by corrugated parakeratinized stratified squamous epithelium resting on a basal cell layer composed of columnar cells exhibiting palisaded hyperchromatic nuclei, features consistent with OKC. Surgical treatment consisted of bilateral crestal and crevicular incision, a reflection of the flap, breaking of all OKC locules, creation of a continuous cavity, and fitting of a decompression mold around the mandibular teeth. This case highlights the importance of knowing the features of PIOC and considering PIOC in the differential diagnosis of malignant tumors of odontogenic epithelium for timely surgical treatment.

[Surgical removal of an atypically large extensive radicular cyst in the mandible: a case report.] / Atypisch grosse radikuläre Zyste. Operative Entfernung einer atypisch grossen ausgedehnten radikulären Zyste im Unterkiefer, ein Fallbericht.

The radicular cyst is the most common odontogenic cyst and is caused by inflammation. It can become atypically large, although the size of the radiographic osteolysis says nothing about the entity of the lesion. This case shows an unusually large multilocular radicular cyst expanding buccally from tooth 46 in a patient with severe autism who can only be treated under general anesthesia. The clinical and radiological picture as well as the intraoperative situation was more indicative of an aggressive cyst or benign tumor. The lesion was surgically completely removed and the teeth 46, 47 and 48 were extracted because of poor compliance and prognosis. Histopathology revealed a radicular cyst. There were no postoperative complications. After eight months, the lesions had almost completely reossified.

Detection and Segmentation of Radiolucent Lesions in the Lower Jaw on Panoramic Radiographs Using Deep Neural Networks.

Background and Objectives: The purpose of this study was to develop and evaluate a deep learning model capable of autonomously detecting and segmenting radiolucent lesions in the lower jaw by utilizing You Only Look Once (YOLO) v8. Materials and Methods: This study involved the analysis of 226 lesions present in panoramic radiographs captured between 2013 and 2023 at the Clinical Hospital Dubrava and the School of Dental Medicine, University of Zagreb. Panoramic radiographs included radiolucent lesions such as radicular cysts, ameloblastomas, odontogenic keratocysts (OKC), dentigerous cysts and residual cysts. To enhance the database, we applied techniques such as translation, scaling, rotation, horizontal flipping and mosaic effects. We have employed the deep neural network to tackle our detection and segmentation objectives. Also, to improve our model's generalization capabilities, we conducted five-fold cross-validation. The assessment of the model's performance was carried out through metrics like Intersection over Union (IoU), precision, recall and mean average precision (mAP)@50 and mAP@50-95. Results: In the detection task, the precision, recall, mAP@50 and mAP@50-95 scores without augmentation were recorded at 91.8%, 57.1%, 75.8% and 47.3%, while, with augmentation, were 95.2%, 94.4%, 97.5% and 68.7%, respectively. Similarly, in the segmentation task, the precision, recall, mAP@50 and mAP@50-95 values achieved without augmentation were 76%, 75.5%, 75.1% and 48.3%, respectively. Augmentation techniques led to an improvement of these scores to 100%, 94.5%, 96.6% and 72.2%. Conclusions: Our study confirmed that the model developed using the advanced YOLOv8 has the remarkable capability to automatically detect and segment radiolucent lesions in the mandible. With its continual evolution and integration into various medical fields, the deep learning model holds the potential to revolutionize patient care.

Psammomatoid ossicles in odontogenic keratocyst: A rare and unusual phenomenon.

The Odontogenic Keratocyst (OKC) is characterized by pathognomonic histomorphological features and rarely exhibits significant deviations. We present a case of OKC of mandibular posterior region in a 25-year-old female patient. In addition to the classical histopathological characteristics of OKC, the connective tissue near the juxta-epithelial area displayed numerous small round basophilic calcifications resembling psammomatoid ossicles. These calcifications displayed a focal distribution pattern, with round calcifications evenly spaced from each other. Some of these round calcified bodies bore a resemblance to Liesegang ring calcifications. The presence of psammomatoid ossicles in this specific OKC challenges established knowledge, emphasizing the necessity for more comprehensive investigations into these cystic variants especially related to their biological behavior.

Multiple odontogenic keratocysts in a patient with Lowe syndrome: a first case report and literature review.

Lowe syndrome (LS) is a rare disease (1:500,000) with X-linked recessive inheritance involving the kidneys, eyes, and nervous system. A Mexican 25-year-old male patient presented for diagnosis of multiple radiolucent lesions observed on routine radiographic examination. General aspects revealed cognitive delay, eye alterations, and kidney involvement, which support the diagnosis of LS. Radiolucent well-delimited lesions were observed in both mandibular angle and symphysis. Under general anesthesia, incisional biopsy and decompression were performed. Histological aspects led to diagnosing odontogenic keratocyst (OKC) for all lesions. The lesions in the right and left mandibular angles were decompressed, and the symphyseal lesion was enucleated. A 2-month follow-up shows the bone healing process. There are few reports detailing oral findings in LS. Here, we reported the first case of multiple OKC in a patient with LS. In addition, we performed a literature review on odontogenic lesions in patients affected by LS.

Sociodemographic and clinical characterization of cases of 1,103 non-syndromic and 66 syndromic odontogenic keratocyst: a Brazilian multicenter study.

OBJECTIVES: This multicenter study aimed to evaluate cases of non-syndrome and syndromic odontogenic keratocyst, as well as cases of recurrence within these two groups. METHODS: This descriptive, analytical, retrospective cross-sectional study evaluated the sex, age and presence of multiple lesions in 1,169 individuals seen at 10 Brazilian oral and maxillofacial pathology centers. Of these, 1,341 odontogenic keratocysts were analyzed regarding clinical diagnosis, size, site, imaging appearance, signs and symptoms, type of biopsy, treatment, and recurrence. RESULTS: There was a similar distribution by sex. The median age of non-syndromic and syndromic patients was 32 and 17.5 years, respectively. The posterior mandible was the site most affected by small and large lesions in both groups and in recurrent cases. Unilocular lesions were more frequent, also in recurrent cases. Mainly small lesions showed this imaging appearance. Signs and symptoms were absent in most cases. Conservative treatment was the most frequent modality in all age groups, regardless of the patient's condition and recurrence. Recurrences were uncommon. CONCLUSION: This study showed a higher frequency of non-syndromic keratocysts in the population. Clinicopathological features related to the involvement of multiple sites, age, and recurrence may differ between syndromic and non-syndromic cases. Furthermore, we found an association between lesion size and some clinical features and between the time interval to recurrence and the syndromic spectrum. CLINICAL RELEVANCE: To contribute to a better understanding of the distribution and association between clinical, imaging, and sociodemographic characteristics in each spectrum of the lesion.

Appearance and recurrence of odontogenic keratocysts.

OBJECTIVE: The purpose of this study was to evaluate the appearance, histopathological features, and recurrence of odontogenic keratocysts (OKCs) from a large single institute registry over a 36-year period. MATERIALS AND METHODS: A total of 226 cases of OKC were identified in 174 patients over a 36-year period in a single institute in Southwestern Finland. Histological specimens were re-evaluated. The patient's age, sex, location, recurrence, and histopathological features of the OKC were the study variables. RESULTS: OKCs occurred more frequently in men, the mean age was 46 years, and the most frequent site was the lower jaw. Recurrence rate was 21%. Histopathologically, inflammation was present in 95% and satellite cysts in 10% of cases. In patients diagnosed with satellite cysts, OKC recurred in 50% of cases, while the corresponding figure for patients without satellite cysts was 17%. CONCLUSIONS: Compared with the literature, patients were older and inflamed cysts were found more frequently. Satellite cysts occurred only in association with chronic inflammation. Based on the results, regular radiographic evaluation is important among patients aged 10-29 years to detect OKCs and to treat them before enlargement, infection, and inflammation. Satellite cysts should be reported and may be a sign of increased risk of OKC recurrence.

Identification of ferroptosis-related proteins in ameloblastoma based on proteomics analysis.

PURPOSE: We used proteomic sequencing and experimental verification to identify the potential ferroptosis-related proteins in ameloblastoma. METHODS: Samples of ameloblastoma (n = 14) and normal gingival tissues (n = 5) were collected for proteomic sequencing to identify differentially expressed proteins (DEPs) in ameloblastoma. Ferroptosis-related genes were downloaded from FerrDb V2, which were then compared with DEPs to obtain ferroptosis-related DEPs (FR-DEPs). A functional enrichment analysis was performed, and a protein-protein interaction network was built. The hub proteins were screened using the Cytoscape software, and potential drugs targeting them were retrieved from the DrugBank database. A hub protein was selected for immunohistochemical validation, and its expression was assessed in ameloblastomas, odontogenic keratocysts, dentigerous cysts, and normal gingival tissues. The primary ameloblastoma cells were cultured to explore the effect of the protein on the migratory properties of the tumour cells. RESULTS: A total of 58 FR-DEPs were screened, and six hub proteins were identified: mTOR, NFE2L2, PRKCA, STAT3, EGFR, and CDH1. Immunohistochemical analysis showed that mTOR expression was upregulated in ameloblastomas compared with that in odontogenic keratocysts, dentigerous cysts, and normal gingival tissues. p-mTOR was highly expressed in ameloblastomas, with a positivity rate of 83.3%. In addition, rapamycin, an inhibitor of mTOR, can inhibit the migratory capacity of primary cultured ameloblastoma cells. CONCLUSION: Our results revealed the ferroptosis-related proteins in ameloblastomas and their underlying biological processes. Additionally, mTOR was overexpressed and was found to be associated with the aggressiveness of ameloblastomas, which may be a potential target for future treatments.

Differential expression of PEA3 in odontogenic cysts and tumors.

BACKGROUND: PEA3 transcription factor has been identified as a downstream target of the MAPK and PI3K pathways, and PEA3 overexpression has been observed in a variety of tumor types. We aimed to evaluate PEA3 expression in odontogenic cysts and tumors and compare the expression among odontogenic lesions. In addition, the correlations between PEA3 expression and clinicopathological characteristics of conventional ameloblastoma and unicystic ameloblastoma were investigated. METHODS: This study was performed on 165 samples of odontogenic cysts and tumors including 20 dentigerous cysts, 20 odontogenic keratocysts, 16 adenomatoid odontogenic tumors, 5 ameloblastic fibromas, 45 unicystic ameloblastomas, and 59 conventional ameloblastomas. The sections were immunohistochemically stained with mouse monoclonal anti-PEA3 antibody and PEA3 expression was evaluated as the immunoreactive score. RESULTS: PEA3 expression was absent in all dentigerous cysts (DCs) and odontogenic keratocysts, while all adenomatoid odontogenic tumors showed either no (75%) or low (25%) expression of PEA3. Most of the ameloblastic fibromas (60%) displayed no PEA3 expression. A high expression of PEA3 was observed in a substantial number of unicystic ameloblastomas (48.9%) and conventional ameloblastomas (49.2%) in our study. PEA3 expression in DCs, odontogenic keratocysts and adenomatoid odontogenic tumors were significantly different from that in conventional ameloblastomas and that in unicystic ameloblastomas (p < 0.05). The expression of PEA3 was significantly different in the age groups of unicystic ameloblastomas and histological subtypes of conventional ameloblastomas (p < 0.05). CONCLUSION: PEA3 overexpression is predominant in unicystic ameloblastomas and conventional ameloblastomas compared to other odontogenic lesions, indicating a pivotal role of PEA3 as a downstream effector of MAPK pathway in these two odontogenic lesions.

Imunoexpressão de clic4, α-sma, e-caderina e vimentina em lesões odontogênicas epitelias benígnas / Immunoexpression of clic4, α-sma, e-cadherin and vimentin in benign epithelial odontogenic lesions

As lesões odontogênicas epiteliais benignas constituem um grupo heterogêneo de lesões. A proteína CLIC4 atua na regulação dos processos de parada de crescimento e apoptose, participando também do processo de transdiferenciação dos fibroblastos em miofibroblastos que passam a expressar α-SMA. Além disso, a expressão de CLIC4 pode interferir no processo de transição epitélio-mesenquima (TEM) em neoplasias. Este trabalho avaliou a imunoexpressão de CLIC4, α-SMA, E-caderina e Vimentina em ameloblastomas (AM) (n = 16), ceratocistos odontogênicos (n = 20) e tumores odontogênicos adenomatóides (TOA) (n = 8). A análise da expressão imunoistoquímica das proteínas CLIC4, E-caderina e vimentina no componente epitelial das lesões e de CLIC4 e α-SMA no tecido conjuntivo foi realizada de forma semi-quantitativa por um avaliador previamente calibrado. A expressão no componente epitelial de CLIC4 foi analisada separadamente no núcleo e no citoplasma, bem como a marcação de E-caderina que foi avaliada na membrana e no citoplasma. As comparações dos percentuais de imunorreatividade em relação aos grupos estudados foram realizadas por meio dos testes não paramétricos de Kruskal-Wallis e Mann-Whitney. Possíveis correlações entre a expressão de CLIC4, α-SMA, E-caderina e Vimentina foram avaliadas por meio do teste de correlação de Spearman. O nível de significância foi estabelecido em 5% (p < 0,05). Foram observados diferentes padrões de marcação entre os grupos analisados, observando-se que a imunoexpressão exclusivamente citoplasmática da CLIC4 no componente epitelial dos AM (p < 0,001) e TOA (p < 0,001) foi significativamente superior a dos CO, não demonstrarando significância estatística entre os AM e TOA. A imunoexpressão (nuclear e citoplasmática) da CLIC4 no revestimento epitelial CO foi significativamente superior à encontrada no componente epitelial dos AM (p < 0,001) e dos TOA (p < 0,001). A imunoexpressão estromal de CLIC4 foi significativamente superior nos AM (p = 0,009) e CO (p = 0,004) quando comparados aos TOA. A imunoexpressao de α-SMA significativamente maior em AM (p = 0,016) e CO (p = 0,034) quando comparados aos TOA. Para a imunoexpressão membranar da E-caderina em CO foi significativamente superior em comparação à encontrada nos AM (p = 0,009) e nos TOA (p = 0,024). Foi observada maior imunoexpressão de E-caderina (membranar e citoplasmática) nos COs, quando comparados aos AM (p < 0,001) e aos TOAs (p < 0,001). A expressão de Ecaderina citoplasmática foi significativamente maior nos AM e TOA (p < 0,001) quando comparados aos CO. Observou-se diferença estatisticamente significativa na imunoexpressão de vimentina entre os casos de AM e os casos de TOA (p = 0,038) e CO (p < 0,001), bem como entre o TOA e CO (p < 0,001). As correlações testadas entre os escores das proteínas estudadas evidenciou que no grupo dos AM foi possível evidenciar moderada correlação positiva e estatisticamente significativa (r = 0,527; p = 0,036) entre a expressão citoplasmática da CLIC4 e a expressão citoplasmática da E-caderina. Também foi verificada fraca correlação negativa e estatisticamente significativa (r = -0,499; p = 0,049) entre a expressão núcleo-citoplasmática da CLIC4 e a expressão citoplasmática da E-caderina nos AM. Além disso, uma moderada correlação positiva e estatisticamente significativa entre a expressão estromal da CLIC4 e a expressão da α-SMA nos AM (r = 0,648; p = 0,007) e nos CO (r = 0,541; p = 0,014). Foi observada forte correlação negativa e estatisticamente significativa (r = -0,813; p < 0,001) entre a expressão da E-caderina e a expressão da vimentina nos AM. Os resultados deste estudo sugerem um potencial envolvimento de CLIC4 no processo de transdiferenciação de miofibroblastos, e que a presença destas células é mais frequentemente associada a lesões de comportamento biológico mais agressivo como os AM e CO, além de uma possível atuação desta proteína na regulação do ciclo celular e na TEM nas lesões estudadas (AU).

Benign epithelial odontogenic lesions constitute a heterogeneous group of lesions. the CLIC4 protein acts in the regulation of growth arrest and apoptosis processes, also participating in the process of transdifferentiation of fibroblasts Into myofibroblasts that begin to express α-SMA. Furthermore, CLIC4 expression can interfere with the epithelialmesenchymal transition (EMT) process in neoplasms. This work evaluated the immunoexpression of CLIC4, α-SMA, e-cadherin and vimentin in ameloblastomas (AM) (n = 16), odontogenic keratocysts (OK) (n = 20) and adenomatoid odontogenic tumors (AOT) (n = 8). The analysis of the immunohistochemical expression of the proteins CLIC4, ecadherin and vimentin in the epithelial component of the lesions and of CLIC4 and α-SMA in the connective tissue was carried out in a semi-quantitative way by a previously calibrated evaluator. Expression in the epithelial component of CLIC4 was analyzed separately in the nucleus and cytoplasm, as well as e-cadherin labeling, which was evaluated in the membrane and cytoplasm. Comparisons of the percentages of immunoreactivity in relation to the studied groups were carried out using the nonparametric kruskal-wallis and mann-whitney tests. Possible correlations between the expression of CLIC4, α-SMA, e-cadherin and vimentin were evaluated using the spearman correlation test. The significance level was set at 5% (p < 0.05). Different staining patterns were observed between the groups analyzed, observing that the exclusively cytoplasmic immunoexpression of CLIC4 in the epithelial component of AM (p < 0.001) and AOT (p < 0.001) was significantly higher than that of OK, not demonstrating statistical significance between the AM and AOT. The immunoexpression (nuclear and cytoplasmic) of CLIC4 in the co epithelial lining was significantly higher than that found in the epithelial component of AM (p < 0.001) and AOT (p < 0.001). Stromal CLIC4 immunoexpression was significantly higher in AM (p = 0.009) and OK (p = 0.004) when compared to AOT. The immunoexpression of α-SMA is significantly higher in AM (p = 0.016) and OK (p = 0.034) when compared to AOT. For e-cadherin membrane immunoexpression in co was significantly higher compared to that found in AM (p = 0.009) and AOT (p = 0.024). Greater immunoexpression of e-cadherin (membrane and cytoplasmic) was observed in OK, when compared to AM (p < 0.001) and AOT (p < 0.001). Cytoplasmic ecadherin expression was significantly higher in AM and AOT (p < 0.001) when compared to OK. A statistically significant difference in vimentin immunoexpression was observed between cases of AM and cases of AOT (p = 0.038) and OK (p < 0.001), as well as between AOT and OK (p < 0.001). The correlations tested between the scores of the proteins studied showed that in the am group it was possible to demonstrate a moderate positive and statistically significant correlation (r = 0.527; p = 0.036) between the cytoplasmic expression of clic4 and the cytoplasmic expression of e-cadherin. A weak and statistically significant negative correlation (r = -0.499; p = 0.049) was also found between the nucleus-cytoplasmic expression of clic4 and the cytoplasmic expression of e- cadherin in AM. Furthermore, a moderate positive and statistically significant correlation between the stromal expression of CLIC4 and the expression of α-SMA in AM (r = 0.648; p = 0.007) and OK (r = 0.541; p = 0.014). Additionally, a strong negative and statistically significant correlation (r = -0.813; p < 0.001) was observed between the expression of ecadherin and the expression of vimentin in AM. The results of this study suggest a potential involvement of CLIC4 in the myofibroblast transdifferentiation process, and that the presence of these cells is more frequently associated with lesions with more aggressive biological behavior such as AM and OK, in addition to a possible role of this protein in the regulation of cell cycle and EMT in the lesions studied (AU).

Comprehensive cornified envelope protein profile of odontogenic keratocysts clarifies the characteristics of non-keratinized oral epithelium.

BACKGROUND: Odontogenic keratocysts constitute 10%-20% of odontogenic cysts and exhibit a distinctive corrugated parakeratinized lining epithelium. Considering that cornified envelope formation is an important phenomenon during keratinocyte differentiation, this study aimed to clarify the characteristics of cornified envelope formation in odontogenic keratocysts. METHODS: We investigated the cellular distribution of cornified envelope-related proteins (transglutaminases and their substrates), as well as the upstream regulatory protein c-Fos, by immunohistochemical analysis of the lining epithelium of 20 odontogenic keratocysts. We examined the corresponding mRNA levels by quantitative polymerase chain reaction. Ten dentigerous cysts served as control non-keratinized cysts. RESULTS: The distributions of transglutaminase and their substrates except loricrin and small protein-rich protein 1a significantly differed between odontogenic keratocysts and dentigerous cysts. There was no significant difference in c-Fos expression between odontogenic keratocysts and dentigerous cysts. The mRNA levels of transglutaminases and their substrates were significantly higher in odontogenic keratocysts than in dentigerous cysts. However, c-Fos mRNA levels did not significantly differ between groups. CONCLUSION: Surprisingly, the overall appearance of cornified envelope-related proteins of odontogenic keratocysts was consistent with the characteristics of non-keratinized oral mucosa identified in previous studies. These findings indicate that the contribution of cornified envelope-related molecules in odontogenic keratocysts is similar to that in non-keratinized oral epithelium, rather than keratinized oral epithelium, suggesting that odontogenic keratocysts are not genuine keratinized cysts. The upregulation of cornified envelope-related genes in odontogenic epithelium could be an important pathognomonic event during odontogenic keratocyst development.

Significance of EGFR investigation in odontogenic keratocyst: a narrative review.

BACKGROUND: The recent classification of odontogenic keratocysts (OKSs) recognized them as benign neoplasms, although previous findings have revealed their aggressive nature. Immunohistochemical and molecular analyses have investigated OKSs, but the role of epidermal growth factor receptor (EGFR) has not been fully investigated, despite the importance of this oncogene in the process of carcinogenesis in tumors of epithelial origin. The EGFR protein is usually overexpressed, and the EGFR gene is mutated or amplified. AIMS OF STUDY: This brief review aims to emphasize the importance of EGFR detection in these types of cysts. METHODS AND RESULTS: It was revealed that the majority of the studies examined EGFR protein expression using immunohistochemical methods; however, considering EGFR gene variants, mutations were less explored in the previous period from 1992 to 2023. Although EGFR gene polymorphisms are clinically important, they were not identified in the present study. CONCLUSIONS: In light of the current significance of EGFR variants, it would be beneficial to examine them in odontogenic lesions. This would enable resolving of discrepancies about their nature, and potentially enhance classifications OKCs in the future.