DNA content and clinicopathological features aid in distinguishing ameloblastic carcinoma from ameloblastoma.

BACKGROUND: Ameloblastoma and ameloblastic carcinoma are epithelial odontogenic tumors that can be morphologically similar. In the present study, we evaluated the DNA content and Ki-67 index in the two tumors. METHODS: The paraffin blocks of the tumors were selected to obtain sections for the immunohistochemical reactions and preparation of the cell suspension for acquisition in a flow cytometer. The Random Forest package of the R software was used to verify the contribution of each variable to classify lesions into ameloblastoma or ameloblastic carcinoma. RESULTS: Thirty-two ameloblastoma and five ameloblastic carcinoma were included in the study. In our sample, we did not find statistically significant differences in Ki-67 labeling rates. A higher fraction of cells in 2c (G1) was correlated with the diagnosis of ameloblastoma, whereas higher rates of 5c-exceeding rate (5cER) were correlated with ameloblastic carcinoma. The Random Forest model highlighted histopathological findings and parameters of DNA ploidy study as important features for distinguishing ameloblastoma from ameloblastic carcinoma. CONCLUSION: Our findings suggest that the parameters of the DNA ploidy study can be ancillary tools in the classification of ameloblastoma and ameloblastic carcinoma.

Globe-shaped central incisors in a patient with otodental syndrome.

Hearing impairments and dental anomalies are found in many genetic syndromes. Otodental syndrome is a rare combination of hearing loss and the presence of a pathognomonic dental phenotype known as globodontia, in which the tooth exhibits an abnormal globe shape. There is no histologic evidence of structural anomalies in the enamel, dentin, or pulp. This report describes the case of a 12-year-old boy who had hearing loss and 2 supernumerary globe-shaped teeth in the sites of the permanent maxillary central incisors. The diagnosis of otodental syndrome was established based on the clinical, radiographic, and histologic features, but other conditions, including dens evaginatus, talon cusp, dens invaginatus, and compound odontoma, should be included in the differential diagnosis. Dental treatment consisted of the extraction of both anomalous teeth, allowing spontaneous eruption of the impacted permanent central incisors. Early diagnosis of otodental syndrome permits a multidisciplinary approach to prevent other pathologic conditions, reduce functional damage, and avoid social problems.

Interrogation of TERT promoter hotspot mutations in ameloblastoma and ameloblastic carcinoma.

BACKGROUND: TERT promoter mutations increase telomerase activity, conferring cell immortality. The coexistence of TERT promoter mutations with BRAFV600E is associated with aggressiveness. Ameloblastoma and ameloblastic carcinoma are infiltrative neoplasms that harbor BRAFV600E; however, it remains unknown if these odontogenic tumors also show TERT promoter mutations. METHODS: Genomic DNA of paraffin-embedded ameloblastomas (n = 6) and ameloblastic carcinomas (n = 3) were Sanger-sequenced to assess the hotspot TERT promoter mutations C228T and C250T. BRAFV600E status was screened by TaqMan allele-specific quantitative polymerase chain reaction. RESULTS: None of the samples harbored TERT promoter mutations. The BRAFV600E mutation was positive in 3 of 6 of ameloblastomas and in 1 of 3 of ameloblastic carcinomas. CONCLUSION: The absence of TERT promoter mutation in the samples indicates that this molecular event is not relevant to the tumors' pathogenesis. Further studies are necessary to explore undefined genetic or epigenetic mechanisms related to TERT-upregulation in ameloblastoma, and the telomerase activity in ameloblastic carcinoma.

Synchronous odontogenic tumors: A systematic review.

This systematic review aimed to incorporate published information about synchronous odontogenic tumors (SOTs) with an analysis of the demographic and clinical characteristics from the cases published in the literature. Case reports and case series of SOT were searched in PubMed, Web of Science, Scopus, and EMBASE. A descriptive statistical analysis was performed. Twenty-eight studies comprising 30 cases of SOTs were included. Considering all cases published, SOTs mostly occurred simultaneously in the maxilla and mandible (n = 19/63.3%). Lesions were bifocal in 13 (43.3% of all the 30 cases) and multifocal in 17 cases (56.7% of all the 30 cases). All SOTs available in the literature presented the same type of lesion, and two of them also involved another different SOT (n = 2/6.7% of all the 30 cases). Out of all published cases, the most frequent SOTs in the literature were odontomas (n = 10/33.3% of all the 30 cases), squamous odontogenic tumors (OTs) (n = 8/26.7% of all the 30 cases), calcifying epithelial OTs (n = 8/26.7% of all the 30 cases), and adenomatoid OTs (n = 2/6.7% of all the 30 cases). Considering all SOTs cases included, the overall recurrence was 13.3%. Inside a subgroup of the lesion, synchronous calcifying epithelial OT presented the highest (25%). Five cases (16.7% of all the 30 cases) had a previously associated syndrome, with two cases of Schimmelpenning syndrome being reported. Among published SOTs, odontomas were the most common. All SOTs available in the scientific literature showed the same type of OT and mainly affected both jaws simultaneously. Only a few of these cases were associated with a syndrome.

Salivary biomarkers to evaluate psychological disorders in oral lichen planus: A systematic review with meta-analysis.

OBJECTIVE: To analyze the use of salivary biomarkers to identify psychological disorders (anxiety, depression, and stress) in individuals with oral lichen planus (OLP). MATERIALS AND METHODS: The search was made in Medline/Pubmed, Scopus, Web of Science, Virtual Health Library, ProQuest, and by cross-reference. Original case-control, cross-sectional, and cohort studies, in human subjects (age ≥18 years) with clinical and histopathological diagnosis, with or without the use of psychometric scales, published until June 2021, were included. Random-effects meta-analyses, subgroup analyses, and sensitivity were performed. Publication bias was measured using the Egger test and visual inspection of the funnel plot. RESULTS: A total of 67 articles were found, of which 12 were included in the meta-analysis. Among the different biomarkers identified, it was only possible to perform a meta-analysis for cortisol. The mean difference between salivary cortisol levels in patients with OLP compared to controls was 3.43 ng/ml (95% CI: 1.20-5.65) with I2  = 98.9%. Studies considered outliers were removed and based on sensitivity analyses, results did not change, therefore, being stable. CONCLUSION: The studies analyzed demonstrated that cortisol was the most quantified biomarker to identify psychological disorders; however, DHEA, IgA, adiponectin, and α-amylase were also evaluated.

Effects of Violet and IR LED Light on mast cell degranulation: in vivo study in a murine model.

The aim of this study was to evaluate the influence of IR (λ850 ± 10 nm) and violet (λ405 ± 10 nm) LED phototherapy on total mast cells counts and its ability to influence mast cell degranulation. For this, 27 Wistar rats were used and were randomly distributed into three groups: control, IR LED, and violet LED. When indicated, irradiation done and they were sacrificed, had their tongue removed immediately, 20-min, 45-min, and 2-h after irradiation. Samples were processed to wax, cut, and stained with Toluidine Blue. Intact and degranulated mast cells were counted under light microscopy, and statistical analysis was carried out. In the superficial connective tissue and muscular tissues, violet LED light caused a significant increase in both total number and degranulated mast cells when compared to the control group immediately after irradiation. The degranulation indexes were higher in the groups irradiated with Violet light, both in superficial connective tissue and muscular tissues in relation to the timing. Irradiation with IR LED caused immediate increase in the total number and degranulated of mast cells when compared to the control group only in the superficial connective tissue. In all times observed, the highest total amount of mast cells was seen immediately after irradiation, except in the muscular tissue, which presented the highest amount after 20-min. It was concluded that IR and violet LED light were able to increase the number of mast cells and inducing degranulation in oral mucosa. However, considering that violet LED light can be harmful in periodontal disease, it seems that the use of IR LED light could be the best option in Dentistry.

Impact of serum vitamin D levels on periodontal healing outcomes: A preliminary cohort study.

OBJECTIVE: To evaluated the relationship between serum vitamin D levels and periodontal healing outcomes in patients with mild or moderate periodontitis. METHODS: Serum vitamin D levels and periodontal pockets and gingival bleeding were evaluated in 51 patients before and 6 months after non-surgical periodontal treatment. A t-test and chi-square test were used to analyse the data (p ≤ 0.05). RESULTS: The mean reduction of periodontal pocket depth was statistically significant higher in patients with vitamin D ≥30 ng/ml than those with <30 ng/ml (CI = -0.23-0.42, p = 0.05), but not clinically significant. Vitamin D level was not associated with the percentage of sites of gingival bleeding on probing at the final evaluation (OR = 0.58, 95% CI = 0.17-1.99, p = 0.39). CONCLUSION: Lower serum vitamin D level was associated with a slightly reduced periodontal healing after non-surgical periodontal therapy, which should be further investigated in a larger population.

Chlorhexidine mouthwash reduces the salivary viral load of SARS-CoV-2: A randomized clinical trial.

OBJECTIVES: This study aimed to evaluate the effect of 0.12% chlorhexidine gluconate on the salivary load of SARS-CoV-2. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was performed on 100 participants positive for SARS-CoV-2. In the test group (n = 50), volunteers gargled with a mouthwash containing 15 ml of 0.12% chlorhexidine gluconate for 1 min, while the control group (n = 50) used a placebo. Saliva samples were obtained before (baseline) and 5 and 60 min after using the solutions. Real-time reverse transcription polymerase chain reaction assays (qRT-PCR) were carried out and the cycle threshold (Ct) was computed. The chi-square test and t-test were used for group comparison (p ≤ 0.05). RESULTS: The differences in Ct values between the 5-min evaluation and baseline (test group: 2.19 ± 4.30; control: -0.40 ± 3.87, p = 0.002) and between 60 min and baseline (test group: 2.45 ± 3.88; control: 0.76 ± 4.41, p = 0.05) were significantly greater in the test group, revealing a reduction of viral load. Furthermore, there was a reduction in the load of SARS-CoV-2 in 72% of the volunteers using chlorhexidine versus 30% in the control group (p = 0.001). CONCLUSIONS: Chlorhexidine gluconate (0.12%) was effective in reducing salivary SARS-CoV-2 load for at least 60 min.

Impact of the COVID-19 pandemic on public University laboratories of oral and maxillofacial pathology: A Brazilian multicenter study.

OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on the number of diagnoses of oral and maxillofacial lesions in public laboratories after one year of COVID-19 outbreak in Brazil. MATERIAL AND METHODS: This is a cross-sectional study. Biopsies submitted to histopathologic examination from March 2019 to February 2020 (pre-pandemic period) and from April 2020 to March 2021 (pandemic period) in nine Brazilian public oral pathology laboratories were retrieved and the number of diagnoses, types of lesion, and percentage changes during both periods were analyzed. RESULTS: There were 7389 diagnoses in the pre-pandemic period and 2728 in the pandemic era, indicating a reduction of 63.08%. The reduction was 64.23% for benign lesions and 49.48% for malignant lesions, with a 50.64% reduction in squamous cell carcinoma. The largest decreases were observed in April 2020 and January 2021. CONCLUSION: An important reduction in the diagnoses of benign and malignant lesions was noted in the Brazilian public oral pathology laboratories during the first year of the COVID-19 pandemic.

Adenoid ameloblastoma with dentinoid is molecularly different from ameloblastomas and adenomatoid odontogenic tumors.

BACKGROUND: Adenoid ameloblastoma is a rare epithelial neoplasm, histologically characterized by the presence of ameloblastoma-like features, duct-like structures, epithelial whorls, and cribriform architecture. Dentinoid material is usually present. Some advocate adenoid ameloblastoma is an ameloblastoma variant. However, there are overlapping features not only with ameloblastoma, but also with adenomatoid odontogenic tumor. Most ameloblastomas are characterized by the presence of BRAF p.V600E mutations and adenomatoid odontogenic tumors harbor signature KRAS mutations. The molecular features of adenoid ameloblastoma remain unknown. METHODS: Nine adenoid ameloblastoma cases were screened by TaqMan allele-specific qPCR to assess BRAF p.V600E, ameloblastoma signature mutation, and KRAS p.G12V and p.G12R, adenomatoid odontogenic tumor signature mutations. RESULTS: BRAF and KRAS mutations were not detected in any of the adenoid ameloblastoma cases. CONCLUSION: The molecular results support adenoid ameloblastoma as an entity distinct from adenomatoid odontogenic tumor and ameloblastoma.

A multicenter study of oral sarcomas in Brazil.

OBJECTIVES: The aim of this study was to investigate the prevalence of oral sarcomas from geographic regions of Brazil. MATERIALS AND METHODS: A cross-sectional study was conducted on biopsies obtained from January 2007 to December 2016 at twelve Brazilian oral and maxillofacial pathology centres. Gender, age, evolution time, clinical aspects, tumour location, tumour size at diagnosis, radiographic aspects and histopathological diagnosis were evaluated. Data were analysed using descriptive statistical methods. RESULTS: From 176,537, a total of 200 (0.11%) oral sarcomas were reported, and the most prevalent were osteosarcomas (74 cases; 37%) and Kaposi's sarcomas (52 cases; 26%). Males were more affected than females at a mean age of 32.2 years old (range of 3-87 years). The most common symptoms were swelling¸ localised pain and bleeding at a mean evolution time of 5.14 months (range <1-156 months). The lesions were mostly observed in the mandible (90 cases; 45%), with a mean tumour size of 3.4 cm (range of 0.3-15 cm). Radiographically, the lesions presented a radiolucent aspect showing cortical bone destruction and ill-defined limits. CONCLUSIONS: Oral sarcomas are rare lesions with more than 50 described subtypes. Osteosarcomas and Kaposi's sarcomas were the main sarcomas of the oral cavity in Brazil.

Central giant cell granuloma: A clinicopathological and immunohistochemical study of macrophages, blood vessels, lymphatic vessels and regulatory proteins.

OBJECTIVE: This study seeks to investigate immunohistochemical parameters that could distinguish non-aggressive Central giant cell granuloma (CGCG) from aggressive CGCG, two groups of lesions which differ in their clinical and radiographic features and prognosis. MATERIAL AND METHODS: 12 cases of non-aggressive CGCG and 11 cases of aggressive CGCG were investigated and associated the immunohistochemical expression of macrophages (CD68 and CD163), blood vessels (CD34 and CD105), lymphatic vessels (D2-40) and regulator proteins (p63 and Ki-67). Clinical and radiographic features were also studied. RESULTS: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (p > 0.05). With respect to non-aggressive CGCG, there were no significant correlations, while in aggressive CGCG there was a significant positive correlation between CD68 and CD163 (p = 0.031), between CD34 and D2-40 proteins (p = 0.04), whereas a significant negative correlation was observed between CD105 and CD68 (p = 0.040). However, regardless of aggressiveness of CGCG, there was a significant positive correlation between CD68 and CD163 (p = 0,04). Among the clinical and immunohistochemical aspects, only the symptomatology was a significant risk factor for the occurrence of aggressive CGCG (OR = 12.00/p = 0.016). CONCLUSION: Macrophages and angiogenesis contribute to their maintenance and development of CGCG. In addition, immunohistochemistry used here was not able to differentiate their aggressiveness. However, symptomatology was proved to be a risk factor for the occurrence of aggressive CGCG. It is possible that clinical features, particularly symptomatology, represent the most appropriate parameter to attempt to distinguish GCCG.

Potential role of Hedgehog signaling pathway and myofibroblastic differentiation in central giant cell granuloma-A preliminary study.

OBJECTIVE: This study investigated components of the Hedgehog (HH) signaling pathway (SHH, GLI1), cyclin D1, and smooth muscle actin (SMA) in central giant cell granulomas (CGCG). The relationship between these proteins and myofibroblasts was also studied. MATERIAL AND METHODS: Twelve cases of non-aggressive CGCG and 11 cases of aggressive CGCG were studied using immunohistochemistry for SHH, GLI1, Cyclin D1, and SMA. RESULTS: Associations between all proteins in non-aggressive and aggressive CGCG were not significant (P > .05). All cases of CGCG showed significantly higher expression of SMA compared with the other proteins (P < .01). A positive correlation (P = .04) was only observed between SHH and GLI1 for all cases of CGCG. Furthermore, a positive correlation between SHH and GLI1 in non-aggressive CGCG (P = .04) and between GLI1 and cyclin D1 in aggressive CGCG (P = .03) were observed. There was also a negative correlation between the expression of SHH and SMA in non-aggressive CGCG (P = .031). CONCLUSIONS: This study provided insights into the activation of the HH signaling pathway in CGCG. In addition, the activation of this pathway (SHH and GLI1) might play some role in the differentiation of stromal myofibroblasts, although these markers including Cyclin D1 and SMA do not indicate aggressiveness of the CGCG. Furthermore, this myofibroblastic differentiation process would occur at the expense of maturation of these lesions.

Glypican-3 distinguishes aggressive from non-aggressive odontogenic tumors: a preliminary study.

BACKGROUND: Glypican-3 is a cell surface proteoglycan that is found in embrionary tissues, and there are no studies investigating this protein in odontogenic tumor. Thus, the aim of this study was to investigate glypican-3 in a series of aggressive and non-aggressive odontogenic tumors. METHODS: Fifty-nine cases of tumors were divided into aggressive odontogenic tumors (20 solid ameloblastomas, four unicystic ameloblastoma, 28 KOTs including five associated with Gorlin-Goltz syndrome) and non-aggressive odontogenic tumors (five adenomatoid odontogenic tumors and two calcifying cystic odontogenic tumors) and analyzed for glypican-3 using immunohistochemistry. RESULTS: Glypican-3 was observed in seven solid ameloblastoma and eighteen keratocystic odontogenic tumors including three of the five syndromic cases, but there was no significant difference between syndromic and sporadic cases (P > 0.05; Fisher's exact Test). All cases of unicystic ameloblastoma (n = 4), adenomatoid odontogenic tumor (n = 5), and calcifying cystic odontogenic tumor (n = 2) were negative. CONCLUSIONS: This provided insights into the presence of glypican-3 in odontogenic tumors. This protein distinguished aggressive from non-aggressive odontogenic tumors.

Laser and LED phototherapy on midpalatal suture after rapid maxilla expansion: Raman and histological analysis.

The aim of this study was to analyze the effect of laser or LED phototherapy on the acceleration of bone formation at the midpalatal suture after rapid maxilla expansion. Forty-five rats were divided into groups at 7 days (control, expansion, expansion and laser irradiation, and expansion and LED irradiation) and into 14 days (expansion, expansion and laser in the 1st week, expansion and LED in the 1st week, expansion and laser in the 1st and 2nd weeks, expansion and LED in the 1st and 2nd weeks). Laser/LED irradiation occurred every 48 h. Expansion was accomplished with a spatula and maintained with a triple helicoid of 0.020-in stainless steel orthodontic wire. A diode laser (λ780 nm, 70 mW, spot of 0.04 cm2, t = 257 s, SAEF of 18 J/cm2) or a LED (λ850 ± 10 nm, 150 ± 10 mW, spot of 0.5 cm2, t = 120 s, SAEF of 18 J/cm2) was applied in one point in the midpalatal suture immediately behind the upper incisors. Raman spectroscopy and histological analyses of the suture region were carried and data was submitted to statistical analyses (p ≤ 0.05). Raman spectrum analysis demonstrated that irradiation increases hydroxyapatite in the midpalatal suture after expansion. In the histological analysis of various inflammation, there was a higher production of collagen and osteoblastic activity and less osteoclastic activity. The results showed that LED irradiation associated to rapid maxillary expansion improves bone repair and could be an alternative to the use of laser in accelerating bone formation in the midpalatal suture.

E-cadherin regulators are differentially expressed in the epithelium and stroma of keratocystic odontogenic tumors.

BACKGROUND: The epithelial-mesenchymal transition (EMT) is the process where cells lose their epithelial features and acquire properties of typical mesenchymal cells. The dissociation of tumor cells due to changes in cell-cell adhesion is one of the key principles of tumor invasion and EMT. Thus, the knowledge of the molecular features of EMT in keratocyst odontogenic tumor (KOT) can provide useful markers to aid in the diagnosis and prognosis and perhaps contribute to an alternative therapeutic approach as it shows an aggressive clinical behavior and high recurrence rates. This study aimed to evaluate the EMT in KOT by the immunoexpression of E-cadherin, N-cadherin, Snail, and Slug and comparing to radicular cysts and dental follicles. METHODS: Thirty-two KOTs, 15 radicular cysts, and 08 dental follicles were used for immunohistochemistry, evaluating the extent, intensity, labeling pattern, cellular compartment in the epithelium and stroma, and the presence of inflammation. RESULTS: E-cadherin was preserved in most cases of keratocystic odontogenic tumor. N-cadherin was increased in the tumor epithelium, a result that was positively correlated with the heterogeneous and nuclear immunoexpression of Slug in the epithelium; Slug also correlated with high Snail immunoexpression. N-cadherin was positively correlated with Slug in the stroma of keratocystic odontogenic tumors. CONCLUSIONS: The high immunoexpression of Snail and nuclear Slug in keratocystic odontogenic tumors suggests these proteins as transcription factors without necessarily participating in 'cadherin switching'. However, the knowledge of their induction of the epithelial-mesenchymal transition in odontogenic tumors is still limited.

Interaction of stromal and microvascular components in keratocystic odontogenic tumors.

OBJECTIVE: Little is known about the interaction of stromal components in odontogenic tumors. Thus, the aim of this study was to investigate mast cells (MCs), myofibroblasts, macrophages, and their possible association with angiogenesis and lymphangiogenesis in keratocystic odontogenic tumors (KCOTs). MATERIAL AND METHODS: Thirty cases of KCOTs were included and analyzed by immunohistochemistry for mast cell tryptase, α-SMA, CD34, CD163, and D240. For comparative purpose, 15 radicular cysts (CRs) and 7 pericoronal follicles (PFs) were included. RESULTS: There was an increase in MCs for RCs and this difference was significant when they were compared to KCOTS and PFs. A significant increase in the density of MFs was observed for KCOTs when compared to RCs and PFs (P = 0.00). No significant difference in CD163-positive macrophages (P = 0.084) and CD34-positive vessels (P = 0.244) densities was observed between KCOTs, RCs, and PFs, although KCOTs showed a higher density of all proteins. Significant difference in lymphatic vessel density was observed for KCOTs when compared to RCs and PFs (P = 0.00). Positive correlation was observed between mast cell tryptase and CD34 in KCOTs (P = 0.025). CONCLUSIONS: A significant interaction between the MC population and CD34-positive vessels in KCOTs supported the hypothesis that MCs and blood vessels contribute to the stromal scaffold of KCOT.

Effect of laser (λ 660 nm) and LED (λ 630 nm) photobiomodulation on formocresol-induced oral ulcers: a clinical and histological study on rodents.

The aim of this study was to evaluate, clinically and histologically, the influence of laser and LED photobiomodulation in the healing of formocresol-induced oral mucosa ulcers of rats. We used 60 Wistar rats in which oral ulcers were induced on the gingiva of the lower incisors. Forty-eight hours after inducing the ulcers, the animals were divided into three groups: laser, LED, and untreated. Animals from the laser group received irradiation with GaAlAs, 660 nm, CW, 40 mW, φ 4 mm(2), 4.8 J/cm(2). Animals from the LED group received irradiation with InGaAIP, 630 nm, 150 mW, 4.8 J/cm(2), 0.8 cm spot. Forty-eight hours after oral ulcer induction, both irradiations were applied in a punctuate manner in the center of the ulcer at 48-h interval until the end of the experimental period. The animals were killed at 3, 5, 7, and 11 days after day 0. The results of the clinical evaluation showed that the laser and LED phototherapies were able to accelerate the healing of formocresol-induced oral ulcers, which occurred first in the laser group (ANOVA, p < 0.05). Histologically, there was a slight variation between LED and laser therapy; therefore, the laser group proved to be effective in accelerating wound healing, especially at 5 days, whereas the LED group was more effective at the end of the experimental period. It was concluded that laser and LED photobiomodulation were effective in accelerating the healing of formocresol-induced oral ulcers in both clinical and histological aspects.

Transcriptional profiles of SHH pathway genes in keratocystic odontogenic tumor and ameloblastoma.

BACKGROUND: Sonic hedgehog (SHH) pathway activation has been identified as a key factor in the development of many types of tumors, including odontogenic tumors. Our study examined the expression of genes in the SHH pathway to characterize their roles in the pathogenesis of keratocystic odontogenic tumors (KOT) and ameloblastomas (AB). METHODS: We quantified the expression of SHH, SMO, PTCH1, SUFU, GLI1, CCND1, and BCL2 genes by qPCR in a total of 23 KOT, 11 AB, and three non-neoplastic oral mucosa (NNM). We also measured the expression of proteins related to this pathway (CCND1 and BCL2) by immunohistochemistry. RESULTS: We observed overexpression of SMO, PTCH1, GLI1, and CCND1 genes in both KOT (23/23) and AB (11/11). However, we did not detect expression of the SHH gene in 21/23 KOT and 10/11 AB tumors. Low levels of the SUFU gene were expressed in KOT (P = 0.0199) and AB (P = 0.0127) relative to the NNM. Recurrent KOT exhibited high levels of SMO (P = 0.035), PTCH1 (P = 0.048), CCND1 (P = 0.048), and BCL2 (P = 0.045) transcripts. Using immunolabeling of CCND1, we observed no statistical difference between primary and recurrent KOT (P = 0.8815), sporadic and NBCCS-KOT (P = 0.7688), and unicystic and solid AB (P = 0.7521). CONCLUSIONS: Overexpression of upstream (PTCH1 and SMO) and downstream (GLI1, CCND1 and BCL2) genes in the SHH pathway leads to the constitutive activation of this pathway in KOT and AB and may suggest a mechanism for the development of these types of tumors.