Does YAP influence cell proliferation and apoptosis in benign epithelial odontogenic lesions?

OBJECTIVE: To analyze the immunohistochemical expression of YAP and its correlation with markers involved in cell proliferation and apoptosis in benign epithelial odontogenic lesions. STUDY DESIGN: The sample consisted of 95 cases of odontogenic lesions (25 dentigerous cysts, 30 non-syndromic odontogenic keratocysts, 30 conventional ameloblastomas, and 10 unicystic ameloblastomas) and 10 dental follicles used as normal odontogenic tissue. The histological sections were submitted to immunohistochemistry with YAP, cyclin D1, Ki-67, and Bcl-2 antibodies. Immunoexpression was analyzed qualitatively and quantitatively using an adapted method. The collected data were analyzed descriptively and statistically (p ≤ 0.05). RESULTS: The highest YAP expression was observed in odontogenic keratocysts, followed by unicystic ameloblastomas and conventional ameloblastomas, which exhibited moderate immunoreactivity predominantly in peripheral cells. Furthermore, significant differences in YAP immunoexpression were observed between the groups analyzed, with significant positive correlations between YAP and cyclin D1 in dentigerous cysts and unicystic ameloblastomas and between YAP and Ki-67 in unicystic ameloblastomas (p < 0.05). However, there were no statistically significant correlations between YAP and Bcl-2 immunoexpression in the groups studied. CONCLUSION: YAP may influence epithelial cell proliferation in odontogenic cysts and tumors, suggesting its possible participation in the progression of the odontogenic lesions studied.

Automatic Classification and Segmentation of Multiclass Jaw Lesions in Cone-Beam Computed Tomography using Deep Learning.

OBJECTIVES: To develop and validate a modified deep learning (DL) model based on nnU-net for classifying and segmenting five-class jaw lesions using cone-beam computed tomography (CBCT). METHODS: A total of 368 CBCT scans (37 168 slices) were used to train a multi-class segmentation model. The data underwent manual annotation by two oral and maxillofacial surgeons (OMSs) to serve as ground truth. Sensitivity, specificity, precision, F1-score, and accuracy were used to evaluate the classification ability of the model and doctors, with or without artificial intelligence assistance. The dice similarity coefficient (DSC), average symmetric surface distance (ASSD) and segmentation time were used to evaluate the segmentation effect of the model. RESULTS: The model achieved the dual task of classifying and segmenting jaw lesions in CBCT. For classification, the sensitivity, specificity, precision, and accuracy of the model were 0.871, 0.974, 0.874 and 0.891, respectively, surpassing oral and maxillofacial radiologists (OMFRs) and OMSs, approaching the specialist. With the model's assistance, the classification performance of OMFRs and OMSs improved, particularly for odontogenic keratocyst (OKC) and ameloblastoma (AM), with F1-score improvements ranging from 6.2% to 12.7%. For segmentation, the DSC was 87.2% and the ASSD was 1.359 mm. The model's average segmentation time was 40 ± 9.9 s, contrasting with 25 ± 7.2 min for OMSs. CONCLUSIONS: The proposed DL model accurately and efficiently classified and segmented five classes of jaw lesions using CBCT. In addition, it could assist doctors in improving classification accuracy and segmentation efficiency, particularly in distinguishing confusing lesions (e.g., AM and OKC).

Dentigerous Cysts in Children: Clinical, Radiological, and Healing Aspects.

Background and Objectives: Dentigerous cysts are one of the most frequent pathologies associated with unerupted or impacted teeth. Such cysts show a male predilection and a preference for the mandibular region. Also, they commonly occur in the second and third decades of life, with only 9% occurring in the first decade. The aim of this work is to apply and study the therapeutic algorithms developed for dentigerous cysts and their outcomes, from the early diagnostic stage to the complete healing phase of pediatric patients diagnosed with this medical condition. Materials and Methods: The study included 19 pediatric patients diagnosed with dentigerous cysts who underwent the enucleation and extraction or conservative attitude of the associated tooth. The bony healing was also followed-up 9 months after the surgery. Results: A higher incidence in the posterior area of the mandible and maxilla was observed, as well as a higher incidence in boys. The 9 months postoperative radiographic assessment showed that the bony defects were completely healed. Conclusions: A thorough understanding of the nature of the lesion backed by a good clinical history and by state-of-the-art radiographic and radiologic examinations can go a long way in helping the surgeon to choose the correct therapeutic approach and to ameliorate the medical condition in the best long-term interest of the young patient. The considered dentigerous cyst cases demonstrated that an early diagnosis and treatment of this pathology is followed by a responsive treatment.

The molecular basis of odontogenic cysts and tumours.

The advances in molecular technologies have allowed a better understanding of the molecular basis of odontogenic cysts and tumours. PTCH1 mutations have been reported in a high proportion of odontogenic keratocyst. BRAF p.V600E are recurrent in ameloblastoma and KRAS p.G12V/R in adenomatoid odontogenic tumour, dysregulating the MAPK/ERK pathway. Notably, BRAF p.V600E is also detected in ameloblastic carcinoma, but at a lower frequency than in its benign counterpart ameloblastoma. Recently, adenoid ameloblastoma has been shown to be BRAF wild-type and to harbour CTNNB1 (ß-catenin gene) mutations, further suggesting that it is not an ameloblastoma subtype. CTNNB1 mutations also occur in other ghost-cell-containing tumours, including calcifying odontogenic cysts, dentinogenic ghost cell tumours and odontogenic carcinoma with dentinoid, but the link between CTNNB1 mutations and ghost cell formation in these lesions remains unclear. Regarding mixed tumours, BRAF p.V600E has been reported in a subset of ameloblastic fibromas, ameloblastic-fibrodentinomas and fibro-odontomas, in addition to ameloblastic fibrosarcoma. Such mutation-positivity in a subset of samples can be helpful in differentiating some of these lesions from odontoma, which is BRAF-wild-type. Recently, FOS rearrangements have been reported in cementoblastoma, supporting its relationship with osteoblastoma. Collectively, the identification of recurrent mutations in these aforementioned lesions has helped to clarify their molecular basis and to better understand the interrelationships between some tumours, but none of these genetic abnormalities is diagnostic. Since the functional effect of pathogenic mutations is context and tissue-dependent, a clear role for the reported mutations in odontogenic cysts and tumours in their pathogenesis remains to be elucidated.

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.

Glandular odontogenic cysts: A collaborative investigation of 22 cases and proteins related to invasiveness.

BACKGROUND: A glandular odontogenic cyst (GOC) has an intriguing, aggressive behaviour whose mechanisms have not yet been clarified. OBJECTIVE: To conduct a collaborative cross-sectional study on the clinical, demographic, microscopic and immunohistochemical characteristics of GOCs, emphasizing the histopathological characteristics and expression of proteins related to invasiveness. METHODS: Twenty-two cases of GOC from three oral and maxillofacial pathology services in Brazil were selected from 1988 to 2018. Clinical and demographic data were collected. Histopathological features were evaluated in detail. Sixteen cases of GOC were also submitted to immunohistochemistry to detect MT1-MMP, TKS4, TKS5 and cortactin, the key regulators of invadopodia formation. RESULTS: Glandular odontogenic cysts were primarily seen in men over 40 years of age, in the posterior mandible and the anterior maxilla as a unilocular, radiolucent lesion. All cases presented hobnail cells, clear cells and variable thickness of the lining epithelium, 3 of the 10 key histopathological parameters to be evaluated in GOCs. Immunohistochemistry revealed a greater expression of the studied proteins in the GOCs than in the controls (p < 0.0001). CONCLUSION: Overexpression of proteins that regulate cell invasiveness was identified, and the present study's findings suggest that invadopodia activity is a possible mechanism used by GOCs to promote local invasion, which could partly explain its intriguing biological behaviour.

Novel recurrence risk stratification of odontogenic keratocysts: A systematic review.

The aim of this study was to identify all clinical, radiological, histopathological, and immunohistochemical features associated with recurrence of odontogenic keratocysts (OKCs) in the literature and formulate a recurrence risk stratification based on these findings. A search was performed in PubMed/Medline, Scopus, Web of Science, Google Scholar and Cochrane databases for clinical and laboratory studies reporting on clinico-pathological features that led to OKC recurrences for the period 2000 to 2020. Twenty-three studies were identified and analyzed qualitatively. A total of 2064 OKCs were included of which 439 OKCs were recurrent with a mean follow-up period of 46.7 months. Significantly associated parameters with OKC recurrence included age (variable age categories), large (>4 cm), multilocular lesions with cortical perforation, association with dentition, presence of daughter cysts, and epithelial budding. Immunohistochemical markers including high Ki67 index and AgNOR count were also implicated. A recurrence risk stratification was formulated based on these findings. Although the level of evidence from the included studies was low, there was considerable evidence that the clinico-pathological parameters identified were linked with higher OKC recurrence. The surgeon, radiologist, and pathologist should aim to identify these features when making a diagnosis so as to determine the appropriate management regime and prevent recurrences.

Recurrence-free survival and prognostic factors of odontogenic keratocyst: a single-center retrospective cohort.

PURPOSE: The aim of the present study was to evaluate the 5-year recurrence-free survival and prognostic factors of odontogenic keratocyst (OKC) from a single-center retrospective cohort in the northeastern region of Brazil. METHODS: Forty cases of OKC comprised the study population. In the cohort analyzed, 18 (45%) cases were recurrent OKCs and 22 (55%) were non-recurrent OKCs. Recurrence-free survival was defined as the period from the release of the histopathological report to the occurrence of relapse or last visit to the service. RESULTS: Comparison of the clinicopathological variables between primary and recurrent OKC lesions revealed no differences in the frequency of epithelial thickness, presence of satellite cysts and cystic spaces, presence of an inflammatory infiltrate, locularity, and lesion borders. The frequency of symptoms was practically the same even after recurrence. Satellite cysts were more frequent in the group of recurrent lesions (n = 9, p = 0.002) and the presence of an inflammatory infiltrate was also significantly associated with recurrent lesions (n = 15, p = 0.006). Previous decompression or marsupialization was associated with recurrence of the lesion (p = 0.010). CONCLUSIONS: In conclusion, the most significant prognostic factors were previous decompression or marsupialization, as well as, morphological parameters associated with the recurrence cases were the presence of an inflammatory infiltrate and satellites cysts. The risk of recurrence is low but continues due to the particularities of epithelial proliferation in OKC.

Surgical Treatment of Voluminous Jaw Cysts with a Buccal Plate: A Study of 20 Clinical Cases.

AIM AND OBJECTIVE: The aim of this paper is to present, with a series of clinical cases, some advantages of a modified surgical technique using fixed bone flaps in an approach to voluminous maxillary or mandibular odontogenic cysts (excluding keratocysts) and highlight the positive impact on the healing of mucus and bone tissues. BACKGROUND: The surgical approach of the enucleation of voluminous maxillary cysts is generally realized with a subtractive osteoplasty. The major problem with this kind of procedure is frequent fibrous healing (or scar formation) of the cavity due to mucosal invagination, especially for large lesions more than 2 cm in diameter. Several techniques have been proposed to limit these side effects. Very contrasting results have been observed in the techniques with graft or exogenous materials, and the scarring effects on mucus and bone tissues are poorly described. In situations where a vestibular cortical bone remains, our modification of the former technique is the use of this bone like a repositioned flap. TECHNIQUE: The present study is a cases series and was carried out on 20 adult patients with maxillary or mandibular cystic lesions larger than 25 mm. For all the patients, our modified technique consisted of using a bone flap to expose more widely the site and to carry out the enucleation of the cyst. Repositioning the flap in the final stage of the operation with osteosynthesis material allowed controlled mucosal and bone healing confirmed by clinical and radiographic follow-up. CONCLUSION: In all cases of our study, no invagination of the soft tissues in the cystic cavity was observed and postoperative bone volumes were identical to the initial state. Only minor postoperative complications were observed in three cases. CLINICAL SIGNIFICANCE: A bone flap approach seems to allow a tissue interception, thus better control of mucosal and bone healing, which is borne out by the clinical and radiographic controls 24 months after surgery.

Retrospective evaluation of cone-beam computed tomography findings of odontogenic cysts in children and adolescents.

BACKGROUND: Odontogenic cysts develop from the epithelium of dental structures and generally grow slowly. In children and adolescents, cysts usually grow faster than adults and require much knowledge for diagnoses and treatments. AIMS: This study aimed to determine the diagnosis and treatment of odontogenic cysts in different age groups by evaluating the type of lesions, age, gender, and anatomical distribution of odontogenic cysts seen in children and adolescents by cone-beam computed tomography. MATERIALS AND METHODS: A total of 42 odontogenic cysts (radicular, dentigerous cyst, and odontogenic keratocyst) were determined in children and adolescents aged 7-18 years. Cone-beam computed tomography images of odontogenic cysts were analyzed in terms of types, age, sex, anatomical location, height, width, depth, scalloped borders, lesion shapes, tooth displacement, root resorption, and association with an unerupted tooth. RESULTS: There was a significant correlation between odontogenic cyst types and age groups, scalloped borders, lesion shape, tooth displacement, root resorption, and association with an unerupted tooth. CONCLUSION: When odontogenic cysts seen in children and adolescents are examined with cone-beam computed tomography, the radicular cyst was the most common form and was predominated in the 13-18 years age group and in boys. Differences in terms of scalloped borders, lesion shape, tooth displacement, root resorption, and association with unerupted teeth were noticed. The knowledge of the distribution and properties of odontogenic cysts in pediatric patients will help diagnose the lesions during clinical and radiological examinations and make appropriate treatment planning.

Prevalence of odontogenic cysts and tumors on turkish sample according to latest classification of world health organization: A 10-year retrospective study.

AIM: The aims of this study are to investigate the prevalence of odontogenic cysts and tumors occurred in a sample of Turkish population in the last 10 years and to compare the data with latest reports. METHODS AND MATERIAL: The present retrospective study was carried out at Gazi University, School of Dentistry (GUSD) in Ankara, Turkey. All the data was retrieved from the GUSD archive on patients treated for various oral and maxillofacial lesions between 2008 and 2018. Patients' demographical data, main clinical features of the lesions along with histopathological findings were retrieved from the dental files of the patients. The type of lesions was evaluated according to the latest Head and Neck Tumor (HNT) classification published by the World Health Organization (WHO) in 2017. Data was analyzed by descriptive statistics and Chi-square test using SPSS version 21.0 software. RESULTS: Among a total of 739 biopsy-conducted lesions, 467 (63.19%) were odontogenic cysts, 43 (5.82%) were benign odontogenic tumors, and 7 (0.95%) were malignant tumors. The rest of 222 cases were defined as others. CONCLUSIONS: The present study assessed the demographic and clinico-pathological characteristics of odontogenic cysts/tumors in a group of Turkish people, who visited GUSD for therapeutic purpose in the past 10 years. Results showed that male patients in their 5th-6th decades have the highest risk of odontogenic cyst/tumor, especially in the mandibular posterior region.

Expression of stem cell markers in stroma of odontogenic cysts and tumors.

BACKGROUND: The stroma of odontogenic cysts/tumors may confer them differential biological behavior. We aimed to investigate the immunoexpression of stem cell markers (Nanog, SOX2, Oct4, and CD34) in the stroma of odontogenic cysts and tumors. CD34 was investigated exclusively as a marker for stromal fibroblast/fibrocyte cells (CD34 + SFCs). CD34 + SFCs were also investigated ultrastructurally. METHODS: Ten cases each of primary odontogenic keratocyst (OKC), recurrent OKC, dentigerous cyst, ameloblastoma, unicystic ameloblastoma, odontogenic myxoma, and 7 syndromic OKC were included. Results were represented as the mean score (%) of positive cells/field for each marker for each study group. For CD34 + SFCs, results are presented as the mean number of cells/field for each type of lesion. Kruskal-Wallis and Spearman's correlation statistical tests were used; significance was set at P < .05. RESULTS: All markers except Oct4 were expressed by stromal cells in all lesions. Expression of SOX2 was significantly higher in tumors than in cysts (P < .05). CD34 + SFCs were more frequent in cysts than in tumors. Ultrastructurally, CD34 + SFCs were identified for the first time in odontogenic lesions and showed characteristic bipolar/dendritic morphology. CONCLUSION: Among examined stromal stem cell markers, only SOX2 distinguished tumors from cysts. CD34 + SFCs may also contribute to the biological behavior of odontogenic lesions.

p16INK4a as a proliferation marker unrelated to HPV expression in odontogenic cysts and tumors.

INTRODUCTION: p16INK4a is a tumor suppressor protein that retards cell cycle progression from G1 to S phase. Prior studies have evaluated p16INK4a expression in odontogenic keratocyst and ameloblastoma, but data regarding other odontogenic cysts and tumors have been sparse. METHODS: With IRB approval, cases from the following entities were identified from archives of the UF Oral Pathology Biopsy Service (2005-2015): benign incidental odontogenic rest, dentigerous cyst, lateral periodontal cyst, calcifying odontogenic cyst, glandular odontogenic cyst, odontogenic keratocyst, orthokeratinized odontogenic cyst, adenomatoid odontogenic tumor, calcifying epithelial odontogenic tumor, and ameloblastoma. All cases were submitted for p16INK4a immunohistochemical testing. RESULTS: Results were scored as follows: nuclear and cytoplasmic staining of <5% cells (score 0), 5%-25% (score 1), 25%-50% (score 2), >50% (score 3). No significant difference in p16INK4a staining was noted between odontogenic cysts and the listed odontogenic tumors (chi-square, P = .540). When comparing lesions with higher recurrence rates (over 25% as reported in the literature) versus lesions with low recurrence rates (under 25%), higher recurrence correlated to significantly higher p16INK4a positivity (chi-square, P = .001). Follow-up testing was performed on 18 cases with "2" or "3" p16INK4a expression scores for high-risk HPV strains through HPV in situ hybridization (ISH) messenger RNA testing with no cases exhibiting a positive result. CONCLUSION: This study exhibits an association between increased p16INK4a positivity and odontogenic lesions with higher recurrence rates and highlights the role of p16INK4a as a progression marker unrelated to HPV expression in this group of pathologic entities.

Diagnosis of cystic lesions using panoramic and cone beam computed tomographic images based on deep learning neural network.

OBJECTIVES: The aim of the current study was to evaluate the detection and diagnosis of three types of odontogenic cystic lesions (OCLs)-odontogenic keratocysts, dentigerous cysts, and periapical cysts-using dental panoramic radiography and cone beam computed tomographic (CBCT) images based on a deep convolutional neural network (CNN). METHODS: The GoogLeNet Inception-v3 architecture was used to enhance the overall performance of the detection and diagnosis of OCLs based on transfer learning. Diagnostic indices (area under the ROC curve [AUC], sensitivity, specificity, and confusion matrix with and without normalization) were calculated and compared between pretrained models using panoramic and CBCT images. RESULTS: The pretrained model using CBCT images showed good diagnostic performance (AUC = 0.914, sensitivity = 96.1%, specificity = 77.1%), which was significantly greater than that achieved by other models using panoramic images (AUC = 0.847, sensitivity = 88.2%, specificity = 77.0%) (p = .014). CONCLUSIONS: This study demonstrated that panoramic and CBCT image datasets, comprising three types of odontogenic OCLs, are effectively detected and diagnosed based on the deep CNN architecture. In particular, we found that the deep CNN architecture trained with CBCT images achieved higher diagnostic performance than that trained with panoramic images.

A Brazilian multicentre study of 2,497 isolated cases of odontogenic keratocysts.

We present the frequency of cases of isolated odontogenic keratocysts submitted to microscopic examination at 10 Brazilian referral centres in Oral and Maxillofacial Pathology. In a retrospective (1953-2017) analysis, data on clinicoradiographic features and treatment of these lesions were collected and analysed descriptively. Among the 258,867 cases retrieved, 2,497 (0.96%) were isolated odontogenic keratocysts. In summary, an overview of individuals affected with isolated odontogenic keratocysts is reported herein. This lesion showed predilection for the posterior mandible of young adult men.

Retrospective 3D analysis of bone regeneration after cystectomy of odontogenic cysts.

BACKGROUND/OBJECTIVE: In this retrospective study, we aimed to investigate a new 3D evaluation method for evaluating bone regeneration after cystectomy of odontogenic cysts. METHODS: The study included 26 patients who underwent cystectomies between 2012 and 2017 and had received either fillings or non-fillings with autologous iliac crest. Bony regeneration was analyzed using 3D imaging software and comparing identical regions of interest (ROIs) that were determined by exact overlays of the postoperative cone beam computer tomography (CBCT) or computer tomography (CT) images. Outcome measures, including volume changes according to the defect size and configuration, patient age, the entity and distribution of the cysts, were collected. RESULTS: Twenty-six patients (5 women and 21 men) had 30 defects, including nine keratocysts, seven radicular cysts and 14 dentigerous cysts. A total of 73% of the defects were in the mandible. The mean 3D follow-up time was 12 months. According to the 3D evaluation of bony regeneration, the defect size and configuration showed no significant differences between the groups (filled or non-filled with 15 defects per group). CONCLUSIONS: By establishing a standardized 3D method for evaluating bone regeneration, healing can be better monitored and evaluated.

Bevacizumab or fibronectin gene editing inhibits the osteoclastogenic effects of fibroblasts derived from human radicular cysts.

Fibronectin (FN) is a main component of extracellular matrix (ECM) in most adult tissues. Under pathological conditions, particularly inflammation, wound healing and tumors, an alternatively spliced exon extra domain A (EDA) is included in the FN protein (EDA+FN), which facilitates cellular proliferation, motility, and aggressiveness in different lesions. In this study we investigated the effects of EDA+FN on bone destruction in human radicular cysts and explored the possibility of editing FN gene or blocking the related paracrine signaling pathway to inhibit the osteoclastogenesis. The specimens of radicular cysts were obtained from 20 patients. We showed that the vessel density was positively associated with both the lesion size (R = 0.49, P = 0.001) and EDA+FN staining (R = 0.26, P = 0.022) in the specimens. We isolated fibroblasts from surgical specimens, and used the CRISPR/Cas system to knockout the EDA exon, or used IST-9 antibody and bevacizumab to block EDA+FN and VEGF, respectively. Compared to control fibroblasts, the fibroblasts from radicular cysts exhibited significantly more Trap+MNCs, the relative expression level of VEGF was positively associated with both the ratio of EDA+FN/total FN (R = 0.271, P = 0.019) and with the number of Trap+MNCs (R = 0.331, P = 0.008). The knockout of the EDA exon significantly decreased VEGF expression in the fibroblasts derived from radicular cysts, leading to significantly decreased osteoclastogenesis; similar results were observed using bevacizumab to block VEGF, but block of EDA+FN with IST-9 antibody had no effect. Furthermore, the inhibitory effects of gene editing on Trap+MNC development were restored by exogenous VEGF. These results suggest that EDA+FN facilitates osteoclastogenesis in the fibrous capsule of radicular cysts, through a mechanism mediated by VEGF via an autocrine effect on the fibroblasts. Bevacizumab inhibits osteoclastogenesis in radicular cysts as effectively as the exclusion of the EDA exon by gene editing.

Gingival cyst of the adult, lateral periodontal cyst, and botryoid odontogenic cyst: An updated systematic review.

The aim of the present review was to integrate the available data published on gingival cyst of the adult (GCA), lateral periodontal cyst (LPC), and botryoid odontogenic cyst (BOC) into a comprehensive analysis of their clinical/radiological features. An electronic search was undertaken in July/2017. Eligibility criteria included publications having enough clinical/radiological/histological information to confirm the diagnosis. A total of 146 publications (157 GCAs, 213 LPCs, 96 BOCs) were included. GCA and LPC presented highest prevalence in the sixth/fifth decades; BOC in the sixth/seventh decades. LPCs were larger lesions than GCAs and GCAs appeared at an older age than LPC. There was no statistically significant difference between them for other factors (location, symptoms, recurrence, follow-up time). In comparison with LPC, BOC lesions were larger, appeared more often in mandible and in older subjects, had more often a multilocular appearance, and presented a higher recurrence rate. Recurrence rates: GCA (3.2%), LPC (2.4%), BOC (21.7%). No factor seems to influence the recurrence rate of GCA or LPC. Multilocular radiological appearance seems to affect the recurrence rate of BOCs. Conservative surgical approaches seem to be enough for GCA/LPC. BOC presents a more aggressive behavior than GCA/LPC. Therefore, treatment of this lesion might involve some kind of adjunctive therapy after enucleation.

Immunohistochemical evaluation of Sonic Hedgehog signaling pathway proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) in sporadic and syndromic odontogenic keratocysts.

AIMS: The aim of this study was to compare the clinical and demographic features of 62 patients presenting sporadic odontogenic keratocysts (OKCs) or OKCs associated with nevoid basal cell carcinoma syndrome (NBCCS). In conjunction with this, we also evaluated the immunohistochemical expression of Shh, Ptch1, Ptch2, Smo, Gli1, Gli2 and Gli3 proteins in 86 OKCs. By doing this, we add to the understanding of the biology of this type of lesion, providing tools that will help facilitate the early diagnosis of NBCCS in those patients where the first manifestation is that of OKCs. METHODS: This is a retrospective study; patients were classified into two groups: group 1 which consisted of those who were not affected by NBCCS (49 patients and 57 OKCs) and group 2 which consisted of those who were diagnosed with NBCCS (13 patients and 29 OKCs). The clinical and demographic features were studied and the immunohistochemical expression of Sonic Hedgehog proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) was analyzed in all samples. RESULTS: There was an increase in the expression of three proteins in the syndromic OKC, when compared to that of sporadic cysts. Shh and Gli1 showed higher cytoplasmic expression, while Smo revealed stronger nuclear and cytoplasmic expressions. CONCLUSION AND CLINICAL RELEVANCE: Our findings suggest that the expression patterns of important Shh pathway proteins can represent valuable markers for early diagnosis of NBCCS-associated OKCs, as the major criterion for the diagnosis of NBCCS is currently based on the late appearance of basal cellular carcinomas. Thus, standardizing a new diagnostic tool for diagnosis of NBCCS could be of great importance in the identification of therapeutic targets. We therefore suggest, as based on our findings, that OKCs showing high expression of Shh, Smo, and Gli1 are potentially associated with NBCCS.