Syndromic Odontogenic Keratocysts Research Articles

STAT3 gene expression in ameloblastomas and odontogenic keratocysts

Introduction/Objective. STAT3 (signal transducers and activators of transcription) is involved in different physiological processes, including cell proliferation and survival. High expression of this protein is observed in various types of cancer. This study aimed to investigate the gene and protein expression of STAT3 in a series of odontogenic cysts and tumors to provide more information about their biological profile. Methods. The STAT3 gene expression at mRNA was quantified by real-time quantitative polymerase chain reaction (RT-qPCR) in 23 odontogenic keratocysts (OKCs) and seven ameloblastomas (AMs), and compared to the non-neoplastic oral mucosa. We also assessed the expression of STAT3 gene at protein levels, using immunohistochemistry, in 43 OKCs and 47 AMs. Results. STAT3 transcripts were found in 96.6% of the tumors studied; however, the gene was downregulated in OKC and AM compared to the non-neoplastic oral mucosa. The STAT3 gene expression at mRNA level was higher in sporadic OKC than in syndromic OKC (p = 0.04). There was no difference in STAT3 gene expression at mRNA level between OKCs and AMs (p = 0.88). Immunostaining of STAT3 revealed no significant difference between sporadic and syndrome OKC (p > 0.05), nor between conventional and unicystic AMs (p > 0.05). Ameloblastomas exhibited significantly higher STAT3 immunostaining than OKCs (p = 0.03). In OKC and AM, STAT3 immunostaining was predominantly cytoplasmic and no difference in the cellular localization of STAT3 was observed between these lesions (p = 0.58). Conclusion. Our findings showed low expression of STAT3 gene in OKCs and AMs in relation to nonneoplastic oral mucosa. However, higher STAT3 immunostaining was observed in AMs compared to OKCs.

Prognostic relevance of clinicopathological factors in sporadic and syndromic odontogenic keratocysts: A comparative study.

Current evidence suggests that nevoid basal cell carcinoma syndrome (NBCCS)-associated odontogenic keratocysts (OKCs) exhibit more aggressive clinical behavior and a higher tendency to relapse. The prognostic efficacy of various markers in sporadic and syndromic OKCs is unclear, and so are the results of studies on the usefulness of immunohistochemistry in distinguishing syndromic from sporadic OKCs. This retrospective study aimed to compare the prognostic relevance of various clinicoradiological and histopathological features, as well as the immunoexpression of COX-2, Bcl-2, proliferating cell nuclear antigen (PCNA), p53, Ki-67, osteoprotegerin (OPG), receptor activator of nuclear factor κ B (RANK) and receptor activator of nuclear factor κ B ligand (RANKL), as well as RANKL/OPG balance between sporadic and syndromic OKCs, and to test their utility in distinguishing the 2 types of OKC. We compared the immunoexpression of the aforementioned markers between 31 sporadic and 12 syndromic OKCs, and tested clinicopathological findings and levels of immunostaining against recurrence. We found a significant association between NBCCS and OKC recurrence. There were significant differences in PCNA, p53 and OPG immunoexpression between sporadic and syndromic OKCs. We also found that recurrent sporadic OKCs were significantly larger and markedly more often associated with cortical perforation. Recurrent sporadic OKCs exhibited COX-2 upregulation, but we failed to demonstrate its prognostic relevance. Recurrent syndromic OKCs showed a markedly higher RANKL > OPG ratio. The NBCCS-associated OKCs are significantly more prone to recur than their sporadic counterparts. Larger size and radiological signs of cortical perforation in sporadic OKCs may indicate a higher risk of recurrence. The COX-2 is upregulated in recurrent sporadic OKCs, whereas recurrent syndromic OKCs exhibit higher RANKL and lower OPG expression; however, these findings have no prognostic relevance. The immunoexpression of p53, PCNA and OPG may help to distinguish syndromic from sporadic OKCs.

Histopathological Comparative Analysis between Syndromic and Non-Syndromic Odontogenic Keratocysts: A Retrospective Study

(1) Background: The aim of this study was to compare the histopathological features of syndromic and non-syndromic odontogenic keratocysts (OKs) using conventional and Confocal Laser Scanning Microscopy (CLSM) with their biological behaviour. (2) Methods: Data from the medical records of 113 patients with histological diagnosis of (single and/or multiple) OKs were collected. Globally, 213 OKs (120 syndromic and 93 sporadic) were retrieved, and their histological slides were re-evaluated with conventional H&E staining and with autofluorescence on the same slides using CLSM (Nikon Eclipse E600 microscope). (3) Results: Syndromic OKs showed more satellite cysts than sporadic cases, as well as a basophilic layer in the basement membrane, which was absent in sporadic OKs; both were highlighted with CLSM. The basement membrane in syndromic OKs appeared amorphous and fragile, thus possibly being responsible for the epithelial detachment and collapse, with scalloped features. Furthermore, the basal epithelial layers in such cases also showed increased cellularity and proliferative activity. All these histological features may possibly justify their higher tendency to recur. (4) Conclusions: CLSM is useful advanced technology that could help to quickly and easily discriminate between syndromic and non-syndromic OKs and to more accurately predict their biological behaviour in order to set fitter clinico-radiological follow-ups for individual patients.

HISTOPATHOLOGIC FEATURES AS STRONG PREDICTOR OF SYNDROMIC ODONTOGENIC KERATOCYSTS

<h3>Introduction</h3> Odontogenic keratocyst (OKC) represents approximately 11% of all odontogenic cysts and may be an early sign of Nevoid Basal Cell Carcinoma syndrome (NBCCS). We aim to identify histologic variations in syndromic OKC in patients under 30 years of age that correlate with the protein patched homolog-1 (PTCH-1) immunohistochemical (IHC) staining. <h3>Materials and Methods</h3> An IRB approved retrospective search of the UF Oral Pathology biopsy service database between 1994-2020 was performed for OKC diagnosed in patients under 30. Demographics, medical history, and histology of all cases were reviewed to confirm diagnosis. PTCH-1 IHC staining was performed on selected tissue samples demonstrating our proposed histologic features. <h3>Results</h3> A total of 554 OKC in patients under 30 were identified. Out of these, 33 OKC from confirmed cases of NBCCS were evaluated as the control group to establish microscopic criteria unique for syndromic OKC. The most prominent features include a variably thickened cystic lining with rete ridges formation, papillary projections, multilayer vacuolization within the lining, scant parakeratin, minimal corrugation, and full thickness hyperchromasia. The study group included 521 patients with no known history of NBCCS. Thirty-four percent of the study group matched the histologic criteria for a syndromic OKC diagnosis. IHC staining intensity scores of 0,1,2,3, with 3 being the strongest transepithelial staining pattern was noted in 8 of 10 stained cases from the control group and in 4 of 36 from the study group. <h3>Conclusion</h3> In this study, we report unique histological features that help discriminate syndromic OKC from sporadic ones. These features correlated well with relatively significant transepithelial PTCH-1 staining and hence may be used as a predictor of NBCCS in routine microscopy. PTCH-1 IHC reactivity in sporadic versus syndromic OKC is not well studied. Future large multicentric studies may be helpful in early and reliable identification of syndromic OKC.

Immunoexpression of CXCL12 and CXCR4 in sporadic and Gorlin-Goltz syndrome-related odontogenic keratocysts.

BackgroundDifferences in the pathogenesis and biological behavior of sporadic and Gorlin-Goltz syndrome-related odontogenic keratocysts (OKCs) have been reported, but the underlying mechanisms are not fully elucidated. Chemokine CXCL12 and its main receptor CXCR4 regulate important events in the pathogenesis of several lesions. Material and MethodsThis study evaluated the immunoexpression of CXCL12 and CXCR4 in sporadic and syndromic OKCs. Twenty-two sporadic OKCs and 22 syndromic OKCs were subjected to immunohistochemistry. The percentages of cytoplasmic (CXCL12 and CXCR4) and nuclear (CXCR4) staining in epithelial and fibrous capsule cells were determined. The results were analyzed statistically using the nonparametric Mann-Whitney test and Spearman correlation test (p<0.05). ResultsHigher cytoplasmic expression of CXCL12 was observed in the epithelial lining and fibrous capsule of sporadic OKCs compared to syndromic OKCs (p<0.001). No statistically significant differences in the cytoplasmic expression of CXCR4 were observed between syndromic OKCs and sporadic OKCs (p>0.05). Compared to syndromic OKCs, sporadic OKCs exhibited higher nuclear expression of CXCR4 in the epithelial lining and lower immunoexpression in the fibrous capsule (p<0.05). In the epithelial lining of syndromic OKCs, positive correlation was observed between cytoplasmic and nuclear expressions of CXCR4 (p=0.003). In the fibrous capsule of syndromic OKCs and sporadic OKCs, cytoplasmic and nuclear expressions of CXCR4 were positively correlated (p<0.001). ConclusionsThe results suggest a potential participation of CXCL12 and CXCR4 in the development of OKCs. The heterogeneous expression of these proteins in syndromic and sporadic OKCs may reflect differences in their pathogenesis and biological behavior. Key words:Odontogenic keratocyst, CXCL12, CXCR4, Immunohistochemistry.

A case of non-syndromic multiple odontogenic keratocyst with isolated dentigerous cyst: A diagnostic conundrum

Odontogenic keratocyst (OKC) is a common developmental odontogenic cyst affecting the maxillofacial region. They can occur in two different forms, either as solitary (non-syndromic OKCs) or as multiple OKCs (syndromic OKCs). Multiple OKCs are usually seen in association with Gorlin–Goltz syndrome or otherwise called nevoid basal cell carcinoma syndrome. However, approximately 5% of patients with OKC have multiple cysts without concomitant syndromic presentation. This article reports a case of multiple OKCs of orthokeratinised variant in a non-syndromic patient along with an isolated dentigerous cyst associated with impacted teeth in one of the quadrants. Simultaneous occurrence of dentigerous cyst along with multiple OKCs may be coincidental. Impacted teeth must be radiographed and evaluated histopathologically to rule out varied lesions and associated complications with them.

A comparative immunohistochemical analysis of cortactin in orthokeratinized odontogenic cyst (OOC), sporadic odontogenic keratocyst (OKC), and syndromic OKC

ObjectivesTo evaluate and compare the immunohistochemical expression of cortactin in the epithelial lining of orthokeratinized odontogenic cyst (OOC), sporadic odontogenic keratocyst (OKC), and syndromic OKC. MethodsFormalin-fixed paraffin-embedded tissue blocks of histopathologically diagnosed cases of OOC, OKC, syndromic OKC, normal buccal mucosa (NBM), and oral squamous cell carcinoma (OSCC) were examined for immunohistochemical expression of cortactin. Clear brown cytoplasmic and membranous staining was considered positive. ResultsA statistically significant difference was observed between OOC and syndromic OKC (p < 0.001), as well as between sporadic OKC and syndromic OKC (p < 0.001). Although not statistically significant, the expression of cortactin was slightly higher in the basal layer of NBM (mean = 0.47), OOC (mean = 0.27), sporadic OKC (mean = 0.47) syndromic OKC (mean = 1.53), and OSCC (mean = 0.67) than in the parabasal layers of NBM (mean = 0.27), OOC (mean = 0.20), sporadic OKC (mean = 0.47), syndromic OKC (mean = 1.27), and OSCC (mean = 0.60). ConclusionThe expression of cortactin in the basal layer may suggest the formation of invadopodia in the basal layer where the invasion mechanism occurs. This finding is further supported by the higher localization of cortactin in areas of epithelial budding and daughter cysts in syndromic OKC, thereby reaffirming its possible association with recurrence.

EXPRESSION OF MESENCHYMAL STEM CELL MARKERS IN THE STROMA OF ODONTOGENIC CYSTS AND TUMORS

Objective To investigate the immunoexpression of stem cell markers (Nanog, SOX2, Oct4, CD34) in odontogenic cysts and tumors. CD34 was investigated as a marker for stromal fibroblast/fibrocyte cells (CD34+SFCs). CD34+SFCs were also investigated ultrastructurally. The physical aggregation of collagen fibers was examined by picrosirius red stain and polarized light. Methods Ten cases each of primary odontogenic keratocysts (OKC), recurrent OKC, dentigerous cysts, ameloblastoma, unicystic ameloblastoma, and odontogenic myxoma and 7 syndromic OKC (sOKC) were included. Results were expressed as the mean number of positive cells per field. Changes (%) in polarization colors of the collagen fibers were assessed pending 90° rotation of the microscope table. Significance was set at P Results All markers except Oct4 were expressed by stromal cells in all lesions. Expression of SOX2 but not Nanog was significantly higher in tumors than in cysts (P Conclusions Stromal cells in odontogenic cysts and tumors seem to contribute to their biological behavior.

Multiple odontogenic keratocyst: A case report and review of literature

Odontogenic keratocysts (OKCs) may occur in two different forms, either as solitary (non syndromic OKCs) or as multiple OKCs (syndromic OKCs). Multiple OKCs are usually associated with Gorlin–Goltz syndrome with features like skin carcinomas and bifid ribs, eye, and neurologic abnormalities. We report a rare case of Gorlin–Goltz syndrome in a 35-year-old male patient who presented with a swelling in lower left back teeth region since 1 week. Apart from these, other findings observed in the patient were frontal bossing, depressed nasal bridge, ocular hypertelorism, prominent supra orbital ridge, and mild mandibular prognathism. On the basis of clinical and radiological evaluation, Enucleation was planned in all the three quadrants and histopathological evaluation revealed multiple OKC’s. Patient was followed-up multiple times for the duration of six months. This case report highlights the important findings and presentation of a rare case of Gorlin Goltz syndrome along with its review of literature. Keywords: Odontogenic keratocyst, Basal cell carcinoma, Bifid ribs, Gorlin Goltz Syndrome.

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

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. 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. 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. Among examined stromal stem cell markers, only SOX2 distinguished tumors from cysts. CD34+SFCs may also contribute to the biological behavior of odontogenic lesions.

IMMUNOEXPRESSION OF DNA BER AND NER PROTEINS IN BENIGN EPITHELIAL ODONTOGENIC LESIONS

Objective: To evaluate DNA base excision repair (BER) in APE-1 and XRCC1; and nucleotide excision repair (NER) in XPF proteins in benign epithelial odontogenic lesions with different biological behaviors. Study design: Thirty solid ameloblastomas (AMEs), 30 isolated odontogenic keratocysts (NSOKCs), 29 syndromic odontogenic keratocysts (SKOCs), 30 dentigerous cysts (DCs; n = 30), and 20 dental follicles (DFs) were evaluated quantitatively for APE-1, XRCC1 and XPF through immunohistochemistry. Results: All the odontogenic lesions studied revealed a statistically significant expression of APE-1 (nuclear), XRCC1 (nuclear), and XPF (nuclear and cytoplasmic) compared with DFs (P

Absence of BRAFV600E immunohistochemical expression in sporadic odontogenic keratocyst, syndromic odontogenic keratocyst and orthokeratinized odontogenic cyst.

Odontogenic keratocyst (OKC) is a unique developmental odontogenic cyst that has the potential to behave aggressively and is associated with the nevoid basal cell carcinoma syndrome. Orthokeratinized odontogenic cyst (OOC) is a distinct, uncommon odontogenic cyst. It significantly differs from OKC not only in its epithelial lining but also in proliferating kinetics, clinical, immunohistochemical and biological behaviour. BRAF gene located on chromosome 7q34 encodes a cytoplasmic serine-threonine kinase. Various immunohistochemical studies have been conducted to express the BRAFV600E gene mutation in various odontogenic cyst and tumours with varying results. The present study was conducted to evaluate the possible role of BRAFV600E in the pathogenesis of sporadic OKC, syndromic OKC and OOC by immunohistochemistry. Formalin-fixed paraffin-embedded (FFPE) tissue blocks of 15 diagnosed cases each of sporadic OKC, syndromic OKC and OOC were retrieved from the archives of Department of Oral Pathology and subjected to immunohistochemical staining for the detection of BRAFV600E mutation using a novel rabbit monoclonal antibody clone RM8. Immunohistochemical analysis showed complete absence of BRAFV600E mutation in all cases of sporadic OKC, syndromic OKC and OOC. The negative immunohistochemical expression of BRAFV600E in sporadic OKC, syndromic OKC and OOC suggests that BRAFV600E plays no role in the pathogenesis of sporadic OKC, syndromic OKC and OOC.

Clinicopathological analysis of 844 cases of odontogenic keratocysts

To investigate the clinicopathologic features and prognostic factors in odontogenic keratocyst (OKC), and to provide new reference for clinic treatment and management of these patients. Clinicopathological data of 844 cases initially diagnosed as or associated with OKC at Department of Oral Pathology, Peking University Hospital of Stomatology from 2000 to 2018 were collected. The cases were divided into 4 groups: sporadic OKCs (intraosseous, cystic lesion irrelevant to nevoid basal cell carcinoma syndrome), syndromic OKCs, solid OKCs and peripheral OKCs. The patients were follow-up for 6 to 216 months and the factors that might relate to recurrence were analyzed. There were 805 cases (95.4%) of sporadic OKCs, 32 cases (3.8%) of syndromic OKCs, 3 cases of solid OKCs and 4 cases of peripheral OKCs. The main age of sporadic OKCs was 36.03 years with the peak at the second and third decades. Ratio of male and female was 1.27:1. The predilection site was the molar and ramus area of mandibular (56.2%). In the study, 428 cases (71.2%) were unilocular in radiography while 28.8% were multilocular. The recurrent rate of enucleation with the follow-up was 20.1% (118/588) while most of them occurred in 1-3 years after surgery. The recurrent rate of multilocular patients (39.0%) was significantly higher than that of the unilocular. Enucleation after marsupialization (43 cases) or enucleation only (545 cases) showed no difference in recurrence (P>0.05). The syndromic OKCs was younger (main 20.97) and preferred to be multiple compared with sporadic OKCs (30/32, 93.7%). The predilection site was also molar and ramus area of mandibular (41.7%). Age and gender distribution of multiple cases had no significant difference with those in sporadic OKCs. More daughter cysts and epithelial islands were seen (56.3% and 17.9%). Furthermore, the recurrent rate was significantly higher than that of the sporadic OKCs (13/29, 44.9%). But there was no evidence of recurrent-related factors. The age of solid and peripheral OKCs, averaged at 45.00 and 65.75 years, were older than others. Four of peripheral OKCs showed no recurrence after enucleation. The recurrence rate of sporadic OKCs after enucleation is 20.1%. The multilocular lesions prefer to be recurrent. There is no significant difference of recurrence with enucleation only or enucleation after marsupialization. Compared with sporadic OKCs, the syndromic patients are younger and easier to be multiple. It tends to be recurrent frequently and rapidly. There are no related factors about recurrence of syndromic patients. The clinicians should considerate comprehensively and make an individual management of therapy and follow-up. Solid and peripheral OKCs are rare and older.

Expression of calretinin in odontogenic keratocysts and basal cell carcinomas: A study of sporadic and Gorlin-Goltz syndrome-related cases

Gorlin-Goltz syndrome (GGS), is an autosomal dominant inherited disorder related to germline mutation of PTCH1 gene, characterised by the presence of multiple developmental anomalies and tumours, mainly basal cell carcinomas (BCC) and odontogenic keratocysts (OKC).We analysed and compared the expression of calretinin in 16 sporadic OKCs, from 15 patients, and 12 syndromic OKCs from 11 patients; in 19 BCC's and 2 cutaneous keratocysts (CKC) belonging to 4 GGS patients, 15 sporadic BCCs and 3 steatocystomas (SC).Calretinin was negative in 10 of 12 syndromic OKCs, focally positive (<5% of cells) in 2; six sporadic OKCs were negative, 6 focally and 4 diffusely positive (p = .02, cases focally and diffusely positive vs. cases negative). All BCCs of 3 GGS patients were negative, the fourth patient presented two BCCs negative and 5 focally or diffusely positive; 7 sporadic BCCs were negative and 8 focally positive (p = NS). Two CKCs resulted negative in one GGS patient; 2 sporadic SCs were positive, and a third was negative.PTCH1 mutations produce an altered PTCH protein and an aberrant activation of Sonic hedgehog (SHH) pathway, leading to tumoral proliferation. It has been demonstrated that treatment of human foetal radial glia cells with SHH reduces, whereas the blockage of SHH increases calretinin expression. We found a lower expression of calretinin in syndromic OKCs compared to sporadic cases. Although calretinin's value in differential diagnosis between sporadic and syndromic tumours appears not crucial, our results shed light on the possible link between SHH dysfunction and calretinin expression in GGS-related tumours.

COMPARISON OF CELLULAR PROLIFERATION AND MELANOCYTES IN NON-SYNDROMIC AND SYNDROMIC ODONTOGENIC KERATOCYSTS

Objective To compare cell proliferation and the presence of melanocytes in non-syndromic and syndromic odontogenic keratocyst (OK). Study Design We studied 20 cases of sporadic OK and 10 cases of OK associated with NBCC. To evaluate cell proliferation and the presence of melanocytes, immunohistochemistry was performed with antibodies against Ki-67 and Melan-A, respectively. Results The OK associated with NBCC presented 23.4% (range 8.6%-36.8%) and the sporadic OK 21.8% (range 7.6%-40.4%) of proliferating cells. This difference was not significant. Cells positive for Melan-A occurred exclusively in 4 of 9 cases of syndromic keratocyst. Conclusions No differences were found in the proliferation between OK associated with NBCC and sporadic. Only in the OK associated with the NBCC, the presence of melanocytes was detected.

Immunoexpression of DNA base excision repair and nucleotide excision repair proteins in ameloblastomas, syndromic and non-syndromic odontogenic keratocysts and dentigerous cysts

ObjectiveTo evaluate the immunoexpression of DNA base excision repair (BER) [apurinic/apyrimidinic endonuclease 1 (APE-1), X-ray repair cross complementing 1 (XRCC-1)] and nucleotide excision repair (NER) [xeroderma pigmentosum complementation group (XPF)] proteins in benign epithelial odontogenic lesions with different biological behaviors. DesignThirty solid ameloblastomas, 30 non-syndromic odontogenic keratocysts (NSOKCs), 29 syndromic odontogenic keratocysts (SKOCs), 30 dentigerous cysts (DCs) and 20 dental follicles (DFs) were evaluated quantitatively for APE-1, XRCC-1 and XPF through immunohistochemistry. ResultsNuclear expression of APE-1 was significantly higher in NSOKCs, SOKCs, and ameloblastomas in comparison to DCs (p < 0.001). Nuclear expression of XRCC-1 was higher in NSOKCs and SOKCs than in DCs (p < 0.05). At the nuclear level, XPF expression was higher in NSOKCs and SOKCs than in DCs and ameloblastomas (p < 0.05). A statistically significant higher expression of APE-1 (nuclear), XRCC-1 (nuclear), and XPF (nuclear and cytoplasmic) was found in all odontogenic lesion samples as compared to DFs (p < 0.05). For all lesions, there was a positive correlation between nuclear expression of APE-1 and XRCC-1 or XPF (p < 0.05). ConclusionsOur results suggest a potential involvement of APE-1, XRCC-1 and XPF proteins in the pathogenesis of benign epithelial odontogenic lesions, especially in those with more aggressive biological behavior, such as ameloblastomas, NSOKCs, and SOKCs. We also showed that the expression of APE-1 was positively correlated with the nuclear expression of XRCC-1 and XPF, which may suggest an interaction between the BER and NER pathways in all odontogenic lesions studied herein.

Immunohistochemical Evaluation of Shh Signaling Pathway Proteins in Sporadic and Syndromic Odontogenic Keratocyst

Immunohistochemical Evaluation of Shh Signaling Pathway Proteins in Sporadic and Syndromic Odontogenic Keratocyst

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

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. 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. 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. 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.

Basal cell nevus syndrome (Gorlin syndrome): genetic insights, diagnostic challenges, and unmet milestones

In this article, we present three clinical case reports on Basal Cell Nevus Syndrome (Gorlin Syndrome). Gorlin syndrome is an inherited medical condition with challenges that manifest in multiple body systems and complicate early diagnosis. We examine the epidemiology of the disease and benefits of genetic testing, molecular pathophysiology, and advancement in the molecular-based therapy of Basal Cell Nevus syndrome. The goal of this paper is to shed light on both unmet challenges and advancements in the management of Gorlin syndrome and to provide a new clinical perspective and guidance for future research.Furthermore, the FDA approved Hedgehog pathway inhibitors Vismodegib and Sonidegib designed for advanced basal cell carcinoma have opened a new door for treatment that may ultimately decrease the number of surgeries for a patient with Gorlin syndrome. The role of these agents in syndromic odontogenic keratocyst has not been studied extensively, but one study found that hedgehog pathway inhibitors decrease the size of syndromic odontogenic keratocyst.Ideal surgical treatment that balances low recurrence rates with low impact on one’s quality of life for syndromic odontogenic keratocyst is another unanswered question for oral and maxillofacial surgeons. Per survey studies, treatment options practiced for syndromic odontogenic keratocyst range from marsupialization to segmental osteotomy. Future studies performed should take a comprehensive long-term approach with at least three years of follow-up in order to determine the most appropriate treatment.

Non-Syndromic Multiple Odontogenic Keratocysts: A Case Report and Comparison with Syndromic Multiple Odontogenic Keratocysts

The Odontogenic Keratocyst (OKC) is a relatively common developmental odontogenic cyst arising from the dental lamina remnants. Multiple OKCs are rare and occur either in syndromic and non-syndromic groups. The Keratocyst demands special consideration because of its aggressive clinical nature and propensity for recurrence. Epithelial proliferation plays a significant role in behaviour of OKC and suggests that more aggressive behaviour is present in case of syndromic OKC than non-syndromic ones. Here we report a case of multiple OKCs in a 20 year old female patient having simultaneous occurrence of cystic lesions in maxilla and mandible without any syndromic manifestations. Comparison between syndromic and non syndromic multiple OKCs is also discussed.