Adenomatoid Tumor Research Articles

EXTRAFOLICULAR ADENOMATOID TUMOR: A CASE REPORT

Adenomatoid odontogenic tumor (AOT) is a relatively uncommon lesion, described as a benign neoplasm of ectodermal origin. It presents as a slow-growing lesion, and is often asymptomatic. It is uncommon in patients older than 30 years. Women are affected about twice as often as men. The extrafollicular variant is when the tumor is not associated with an included tooth, being in an interradicular position, causing, in most cases, root divergence. A 39-year-old male patient with an increase in volume in the lower premolar region, but otherwise asymptomatic, sought help. A radiolucent area was observed adjacent to the first and second lower premolars, in a triangular shape causing a divergence of these teeth without root resorption. Diagnostic hypotheses were AOT and squamous odontogenic tumor. An incisional biopsy was performed and confirmed the diagnosis of AOT. The lesion was submitted to enucleation surgery. After 1 year of follow-up, no signs of recurrence could be observed. Adenomatoid odontogenic tumor (AOT) is a relatively uncommon lesion, described as a benign neoplasm of ectodermal origin. It presents as a slow-growing lesion, and is often asymptomatic. It is uncommon in patients older than 30 years. Women are affected about twice as often as men. The extrafollicular variant is when the tumor is not associated with an included tooth, being in an interradicular position, causing, in most cases, root divergence. A 39-year-old male patient with an increase in volume in the lower premolar region, but otherwise asymptomatic, sought help. A radiolucent area was observed adjacent to the first and second lower premolars, in a triangular shape causing a divergence of these teeth without root resorption. Diagnostic hypotheses were AOT and squamous odontogenic tumor. An incisional biopsy was performed and confirmed the diagnosis of AOT. The lesion was submitted to enucleation surgery. After 1 year of follow-up, no signs of recurrence could be observed.

CALCIFYING EPITHELIAL ODONTOGENIC TUMOR: A CASE REPORT

Calcifying epithelial odontogenic tumor (CEOT) is a rare, benign odontogenic neoplasm with aggressive biologic behavior. A 29-year-old woman presented at the university hospital with a complaint of a painless swelling in the right mandibular region that was fibrous in consistency on palpation. Computed tomography (CT) revealed a well-defined radiolucency (3.5 × 2.8 × 2.0 cm) in the mandibular body, permeated by foci of calcification, associated with the crown of an unerupted molar. Cortical expansion and focal areas of perforation were identified. Based on CT, the differential diagnosis included: calcifying cystic odontogenic tumor, calcifying epithelial odontogenic tumor, ameloblastic fibro-odontoma and adenomatoid odontogenic tumor. The microscopic examination revealed sheets of polyhedral, neoplastic, odontogenic epithelial cells with prominent cellular outlines and intercellular bridges. Calcified areas and eosinophilic amyloidlike material were identified. The diagnosis of CEOT was given. Mandibular segmental resection and reconstruction with titanium plate was performed with no recurrence after 3 years’ follow-up.

SCHIMMELPENNING SYNDROME: A CASE REPORT

A 6-year-old girl with a history of epilepsy was referred due to a mandibular lesion. Physical examination revealed the presence of sebaceous nevi involving skin of the face and neck. Intraoral exam revealed an asymptomatic swelling, firm to palpation, covered by mucosa of normal color, in the anterior mandible. The cone beam tomography revealed a presence of 3 well-defined mixed images, associated with impacted teeth 81, 82, and 42. The lesions were surgically excised and the histologic diagnosis was of adenomatoid odontogenic tumors (AOTs). Considering the multiple intraosseous neoplasms and the neurologic and epidermal affections, the diagnosis of Schimmelpenning syndrome was established. After 4 years, a lesion was found in the anterior region of the maxilla with clinical and imaging aspects similar to those of the previous lesions. After enucleation, the histologic analysis again indicated AOT. In 1 year of follow-up evaluation, no signs of recurrence were found. Support: FAPEMIG.

ADENOMATOID ODONTOGENIC TUMOR: A CASE REPORT WITH EMPHASIS ON HISTOPATHOLOGIC FEATURES

Odontogenic tumors constitute a group of lesions with varied histogenesis and biological behavior. We describe the case of a 15-year-old female patient with an asymptomatic lesion in the anterior mandible discovered incidentally in routine radiographic examination. A well-defined, unilocular radiolucent lesion was found between teeth 42 and 43. Clinical diagnosis was odontogenic cyst, and the lesion was treated by enucleation. Microscopic examination revealed a benign epithelial odontogenic neoplasm, constituted by spindle, cubic, and columnar cells, arranged in islands, cords, rosettes, and duct-like structures, in a fibrous stroma. Clinicopathologic characteristics led to the diagnosis of adenomatoid odontogenic tumor (AOT). We emphasize that the knowledge concerning histopathologic features of AOT contributes to a correct diagnosis and appropriate treatment. Given its favorable prognosis, AOT should be treated by conservative surgical approaches.

Adenomatoid Odontogenic Tumor of Anterior Maxilla; A Case Report

Here, we report a case of adenomatoid odontogenic tumor in anterior maxilla in a young girl aged 14 years. Adenomatoid odontogenic tumor is a rare, benign, and distinct slow-growing odontogenic neoplasm which results in painless expansion of jaws. It usually occurs in the anterior maxilla followed by posterior maxilla and rarely in the mandible with an age range of 3 to 82 years and a relative frequency of 2.2% to 7.1% and showing a female predilection (1.9:1).

Images - Adenomatoid tumor of testis, concerning for malignancy after ultrasound.

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P16INK4a as a proliferation marker unrelated to HPV expression in odontogenic cysts and tumors

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. 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 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. 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.

Fine needle aspiration cytology of epididymal nodules and its corroboration with ultrasonographic-histological findings.

Fine needle aspiration cytology (FNAC) assisted with scrotal ultrasonography is the best preoperative diagnostic modality for palpable epididymal nodules. It also aids in their successive remedial approach as well as serves semi-therapeutically in cystic lesions. The objectives of this study are to recognize the spectrum of pathological conditions giving rise to epididymal nodules, then to compare them with corresponding ultrasound images, and to evaluate the histological features wherever practicable. Total 62 patients underwent FNAC as well as sonographic evaluation for their epididymal nodules. Histopathology was performed in only 20 cases. Epididymitis either caused by tuberculosis (30.6%), or in its acute (11.3%) and chronic (8.1%) forms remained the commonest cytological diagnosis. Neoplastic lesions included mostly adenomatoid tumors (8.1%), and another case of seminomatous spread from ipsilateral testicular primary. Nineteen of the excised masses corroborated with their respective cytodiagnoses. The discrepant lesion was actually a papillary cystadenoma, which was cytologically misinterpreted as adenomatoid tumor. FNAC becomes the first-hand investigative measure for epididymal nodules, by virtue of its early, easy and highly accurate diagnostic implications. It segregates the patients into proper therapeutic protocol and thereby estranges those who really need operative management. When deployed together with ultrasound, the diagnostic accuracy of FNAC improves further.

INTRAOSSEOUS LIPOMA OF THE MANDIBLE

<h3>Background</h3> Intraosseous lipoma (IL) is an uncommon, benign lesion of the bones, making up approximately 0.1% of all primary osseous tumors. Presentation within the jaws remains particularly rare, with no more than 20 cases of mandibular intraosseous lipoma (MIL) documented within the English language literature. Its presentation is often mistaken for other entities, such as anterior Stafne bone defect, traumatic bone cavity, keratocystic odontogenic tumor, adenomatoid odontogenic tumor, and glandular odontogenic cyst. MIL has been documented with variable signs and symptoms and locations, but manifestations in the anterior mandible are especially uncommon. <h3>Discussion/Conclusions</h3> A 33-year-old Hispanic female presented with an incidental finding of a well-defined, intraosseous unilocular radiolucent lesion in the right anterior mandible that was not visible on previous radiographs. The lesion measured 30 × 20 mm, without cortical expansion, and was located apical to teeth #25, #26, and #27, which were asymptomatic. The lesion was enucleated, and the specimen was histologically confirmed to be MIL. This uncommon case of MIL has helped to better describe the features of this rare entity. The medial border of this lesion closely approximated the symphyseal midline, even when the lesion approaches the anterior mandible in only about 20% of described cases. The lesion also presented in the fourth decade of life, below the typical age of the fifth and sixth decades. Features of the current case have not been previously reported, given the small number of cases documented in the literature. Although MIL has a mild behavior and does not require aggressive surgical management, this case illustrates that it may mimic other diseases, given its location in the anterior mandible in a younger patient, thus hindering an accurate diagnosis.

The Significance of Relative Claudin Expression in Odontogenic Tumors.

Claudins are integral to the structure and function of tight junctions. Altered claudin expression has been shown to affect disease behavior and patient prognosis in various neoplasms. The objectives of this study were to analyze the claudin-1, -4 and -7 expression in odontogenic tumors and characterize their expression pattern in distinct tumor cell types in relation to the recurrence potential. Sixty-nine cases of odontogenic tumors, including 43 ameloblastomas (AM), 17 adenomatoid odontogenic tumors (AOT), 6 ameloblastic fibromas (AF) and 3 ameloblastic carcinomas (AC) were investigated for claudin-1, -4 and -7 expression immunohistochemically. The staining was analyzed semi-quantitatively and categorized into 4 levels, based on the percentage of positively stained neoplastic epithelial cells. Claudin-1 was expressed in all AOT and AF cases, whereas most AC (66.7%) showed no expression. The claudin-1 staining was moderate-to-intense in the odontogenic epithelium of AF. In contrast, its staining of ameloblast-like cells and stellate reticulum-like cells in AM was weak. Claudin-7 expression was noted in all tumor types studied, while the expression of claudin-4 was limited and mainly localized in the squamous differentiated cells of AM and AC. AM showed significantly higher claudin-4, but lower claudin-7 expression than AOT. In addition, AC showed diminished claudin-1 immunoreactivity, compared to AOT. Low claudin-1 expression in AM was significantly associated with the increased clinical recurrence. The loss of claudin-1 may underlie the locally invasive nature of AM.

Intraoperative decision preventing orchidectomy

Adenomatoid tumors are regarded as distinctive benign mesothelial neoplasms of the paratesticular region, most commonly occurring at the tail of the epididymidis. Because of its rarity, the clinical and histopathological aspects are discussed. We present the case of 40 years old male patient came to our OPD with complaints of left hemiscrotal swelling since 6 months duration. A clinical diagnosis of testicular neoplasm was made, but the final diagnosis of adenomatoid tumor was made after excision. Due to its low incidence in intrascrotal pathology, we believe it is important for the physician to be aware of this interesting entity in order to make a differential diagnosis from other inflammatory processes and to adopt the proper surgical approach.

Immunohistochemical analysis of MMP-13 and EMMPRIN in epithelial odontogenic lesions.

To investigate the contribution of MMP-13 in tumor aggressiveness, by acting on the reorganization of the extracellular matrix, regulating the biological activity of cytokines in odontogenic epithelial lesions, as well as to evaluate the role of EMMPRIN as an inducer of MMP-13. Twenty solid ameloblastomas (SAs), 10 unicystic ameloblastomas (UAs), 20 odontogenic keratocysts (OKCs), and 20 adenomatoid odontogenic tumors (OATs) were selected. The expression of MMP-13 and EMMPRIN was evaluated in epithelial/connective tissue by determining the score of immunoreactive cells. Higher concentration of MMP-13 was observed in epithelium of SAs and OKCs (p = 0.316), while in connective, MMP-13 was more expressed in OKCs and UAs (p = 0.213). OKCs exhibited the highest immunoreactivity score for EMMPRIN in the epithelium (p = 0.091). In connective tissue, a larger number of immunoreactive cells were observed in OKCs and UACs (p = 0.357). There was a moderate correlation (r = 0.343/p = 0.004) between MMP-13/EMMPRIN in epithelium and strong correlation (r = 0.474/p < 0.001) in connective tissue. We suggest that the OKCs, SAs and UAs presented greater immunoexpression for MMP-13 and EMMPRIN, since they were lesions of more aggressive behavior, with smaller expressions in the AOTs that are admittedly indolent. However, we did not find a statistically significant difference between the expression of MMP-13 and EMMPRIN in lesions studied. The positive correlation found between MMP-13 and EMMPRIN in the epithelial and connective tissue of odontogenic lesions analyzed, seems to be related to the role of EMMPRIN as an inducer of MMP-13 expression.

Clinicopathological Correlation of Uterine Corpus Tumors: A Study of 433 Cases

Uterine corpus tumors are one of the most common reasons for morbidity and mortality of women around the world, and histopathological diagnosis is the key for better management of the patients. To study the histopathology of uterine tumors, classify them as per WHO 2014 classification and correlate with clinical parameters. A five-year study was conducted on 433 histopathologically diagnosed cases of uterine corpus tumors. Benign tumors were the most common (95.6%) followed by malignant (3.9%) and borderline (0.5%). Leiomyoma was the most common benign tumor (91.2%). Majority of the cases were multiparous females (88.6%) in fourth and fifth decades of life (77%) and presenting with heavy menstrual bleeding (35.9%). The most location was intramural (68.9%). Cellular leiomyoma (1.8%) was the most common histologic variant; the secondary change was hyalinization (27.8%). Endometrial carcinoma was the most common malignant tumor (3%) followed by leiomyosarcoma (0.5%) and adenosarcoma (0.2%). Majority of the women with endometrial carcinoma were multiparous (76.9%) and belonging to the age-group of 50–59 years (38.4%). The most common symptom was postmenopausal bleeding (76.9%). Endometrioid carcinoma grade I (75%) was the most common type of endometrial carcinoma. Other lesions were adenomyoma (N = 17), STUMP (N = 2), and one case each of adenomatoid tumor, endometrial stromal nodule and secondary tumor. Benign tumors were more common than malignant tumors. Leiomyoma was the most common benign tumor, and endometrial carcinoma was the most common malignant tumor. Many uterine tumors present with similar clinical features. However, histopathology plays an important role in the accurate diagnosis of different types of tumors and thus helps in providing the patient with appropriate management.

Assessing pathogenic mutations in dental follicles as an attempt to identify early events in odontogenic tumours tumourigenesis

ObjectiveDriver oncogenic mutations have been reported in several benign neoplasms. While ameloblastomas show BRAF p.V600E mutations, adenomatoid odontogenic tumours harbour either KRAS p.G12R or p.G12 V. The lack of understanding of the core molecular changes involved in tumour initiation and progression represents a critical barrier to developing new strategies for cancer detection and prevention. Considering the fact that ameloblastoma and adenomatoid odontogenic tumours can originate from dental follicles, we hypothesized that the BRAF and KRAS mutations might be early events in odontogenic tumours tumourigenesis. We aimed to assess BRAF and KRAS mutations in dental follicles associated with asymptomatic impacted teeth. DesignForty-eight dental follicles containing odontogenic epithelial remnants were included in the study. As ameloblastomas most often occur in the posterior mandible and adenomatoid odontogenic tumours have a predilection for the anterior jaws, we assessed by allele-specific qPCR the presence of BRAF p.V600E in 32 dental follicles associated with impacted 3rd mandibular molar teeth and KRAS p.G12 V and KRAS p.G12R mutations in 16 dental follicle specimens obtained from around impacted anterior teeth. Sanger sequencing was used as an additional method. ResultsNone of the dental follicle cases tested positive for the mutations. ConclusionIn conclusion, we tried to detect the early genetic events associated with odontogenic tumours development in dental follicles, but we were unable to showcase that BRAF p.V600E and KRAS p.G12R or p.G12 V mutations are the early genetic events associated with odontogenic tumours development.

EXPRESSION OF ARGYROPHILIC NUCLEOLAR ORGANIZING REGION COUNTS AND PROLIFERATING CELL NUCLEAR ANTIGEN IN EPITHELIAL ODONTOGENIC TUMORS

INTRODUCTION: Odontogenic tumors are diverse groups of lesions derived from odontogenic tissues. Clinical behavior of these lesions varies widely, ranging from benign to malignant with differences in recurrence rate and growth pattern. A better understanding of the underlying molecular mechanisms will help to predict the course of odontogenic tumors and lead to the development of new therapeutic applications. Nucleolar organizer regions (NORs) are loops of DNA that codify the ribosomal RNA and are considered important for protein synthesis. The NORs stained histochemicaly by silver are named argyrophilic nucleolar organizer regions (AgNOR). Quantification of AgNOR represents a valuable parameter of cell kinetics and therefore cell proliferation. The number of AgNOR sites in malignant cells is significantly greater than those in their normal or benign counterparts. Proliferating cell nuclear antigen (PCNA) is a useful marker of cellular proliferation and DNA replication. Malignant tissue is characterized by an uncoordinated proliferating cell nuclear antigen (PCNA). OBJECTIVES: To evaluate the cell proliferation rate using the expression of Argyrophilic Organizing Region counts and Proliferating Cell Nuclear Antigen in epithelial odontogenic tumors and to assess the usefulness of AgNOR and PCNA as markers in malignant potential of epithelial odontogenic tumors. MATERIALS AND METHODS: This study was done on 45 surgical specimens of epithelial odontogenic tumors and one control specimen from normal tooth germ.The tissue biopsies were processed and paraffin sections were prepared. Hematoxylin and eosin-stained sections were examined for diagnosis. Other sections were subjected to AgNORhistochemical technique and immunohistochemical staining for PCNA. Immunohistochemical staining was performed using a Labeled Strept-Avidin Biotin complex method (LSAB). RESULTS: The mean AgNOR count of tooth germ was 1.21 and the benign odontogenic tumors was 1.862.The highest AgNOR count was recorded in Ameloblastic carcinoma and lowest was seen in adenomatoid odontogenic tumor. Statistically significant difference in AgNOR counts of ameloblastoma and adenomatoid odontogenic tumor, ameloblastoma and calcifying epithelial odontogenic tumor, benign odontogenic tumors and ameloblastic carcinoma were seen. AgNORs in ameloblastic carcinoma were more in number and more widely distributed.The highest mean value of PCNA-positive cell percentage was demonstrated in ameloblastic carcinoma followed by ameloblastoma. A significant difference was noted when the PCNA value of ameloblastoma was compared with that of ameloblastic carcinoma. CONCLUSIONS: AgNOR technique may be considered a good indicator of cell proliferation in epithelial odontogenic tumors.The PCNA expression, along with the clinical features, can predict the aggressiveness, chances of recurrence and malignant potential of these tumors.

Molecular characterization of localized pleural mesothelioma.

Localized pleural mesothelioma is a rare solitary circumscribed pleural tumor that is microscopically similar to diffuse malignant pleural mesothelioma. However, the molecular characteristics and nosologic relationship with its diffuse counterpart remain unknown. In a consecutive cohort of 1110 patients with pleural mesotheliomas diagnosedin 2005-2018, we identified six (0.5%) patients diagnosed with localized pleural mesotheliomas. We gathered clinical history, evaluated the histopathology, and in select cases performed karyotypic analysis and targeted next-generation sequencing. The cohort included three women and three men (median age 63; range 28-76), often presenting incidentally during radiologic evaluation for unrelated conditions. Neoadjuvant chemotherapy was administered in two patients. All tumors (median size 5.0 cm; range 2.7-13.5 cm) demonstrated gross circumscription (with microscopic invasion into lung, soft tissue, and/or rib in four cases), mesothelioma histology (four biphasic and two epithelioid types), and mesothelial immunophenotype. Of four patients with at least 6-month follow-up, three were alive (up to 8.9 years). Genomic characterization identified several subgroups: (1) BAP1 mutations with deletions of CDKN2A and NF2 in two tumors; (2) TRAF7 mutations in two tumors, including one harboring trisomies of chromosomes 3, 5, 7, and X; and (3) genomic near-haploidization, characterized by extensive loss of heterozygosity sparing chromosomes 5 and 7. Localized pleural mesotheliomas appear genetically heterogeneous and include BAP1-mutated, TRAF7-mutated, and near-haploid subgroups. While the BAP1-mutated subgroup is similar to diffuse malignant pleural mesotheliomas, the TRAF7-mutated subgroup overlaps genetically with adenomatoid tumors and well-differentiated papillary mesotheliomas, in which recurrent TRAF7 mutations have been described. Genomic near-haploidization, identified recently in a subset of diffuse malignant pleural mesotheliomas, suggests a novel mechanism in the pathogenesis of both localized pleural mesothelioma and diffuse malignant pleural mesothelioma. Our findings describe distinctive genetic features of localized pleural mesothelioma, with both similarities to and differences from diffuse malignant pleural mesothelioma.

Odontogenic Tumors: Imaging-Based Review of the Fourth Edition of World Health Organization Classification.

The fourth edition of World Health Organization (2017) classified odontogenic tumors according to the tissue of origin. Epithelial odontogenic tumors include ameloblastomas, calcifying epithelial odontogenic tumors, adenomatoid odontogenic tumors, and squamous odontogenic tumors. Mixed epithelial and mesenchymal odontogenic tumors include odontomas, ameloblastic fibromas, dentigenic ghost cell odontogenic tumors, and primordial odontogenic tumors. Mesenchymal odontogenic tumors include cementoblastomas, cement-ossifying fibromas, odontogenic fibromas, and odontogenic myxomas. Malignant odontogenic tumors are either carcinomas or sarcomas. The imaging appearance of odontogenic tumors varies according to its category. Computed tomography and magnetic resonance imaging play an important role in localization, characterization, and extension of odontogenic tumors to the teeth and surrounding tissue.

Abstract 4663: KRAS mutations drive adenomatoid odontogenic tumor and are independent of clinicopathological features

Abstract Adenomatoid odontogenic tumor (AOT) is a benign encapsulated epithelial odontogenic tumor that shows indolent clinical behavior and predilection for young individuals. We have recently reported in a few AOT cases mutations in KRAS, which is a proto-oncogene frequently mutated in cancer types such as lung, pancreas and colorectal adenocarcinomas. We aimed to assess KRAS mutations in the hotspot codons 12, 13 and 61 in a large cohort of AOT samples and to test the association of these mutations with clinical (patients’ age, tumor site, tumor size, follicular or extrafollicular subtypes) and histopathological parameters. A convenience sample of 38 central AOT cases was included in the study. KRAS codon 12 mutations were assessed by TaqMan allele-specific qPCR (p.G12V/R) and/or Sanger sequencing, and codon 13 and 61 mutations were screened by Sanger. Histological tumor capsule thickness was evaluated by morphometric analysis. In addition, the phosphorylated form of the MAPK downstream effector ERK1/2 was investigated. Statistical analysis was carried out to test the association of KRAS mutations with clinicopathological parameters. KRAS c.35G&amp;gt;T mutation, leading to p.G12V, was detected in 15 cases. A novel mutation in AOT, c.34G&amp;gt;C, leading to p.G12R, was detected in 12 cases and the other 11 were wild-type. Codon 12 mutations were not associated with the clinicopathological parameters tested. RAS mutations are known to activate the MAPK pathway and we show AOTs express phosphorylated ERK1/2. In conclusion, a high proportion of AOT (27/38, 71%) have KRAS codon 12 mutations, which occur independently of the clinicopathological features evaluated. Collectively, these findings indicate that KRAS mutations and MAPK pathway activation is a common feature of AOT and some cancer types. Although it is unclear why different codon 12 alleles occur in different disease contexts and the complex interactions between tumor genotype-phenotype need clarification, on the basis of our results the presence of KRAS p.G12V or p.G12R can favor the AOT diagnosis in challenging oral neoplasm cases.Acknowledgements: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001 and CNPq/Brazil. Citation Format: Carolina C. Gomes, Bruna P. Coura, Vanessa F. Bernardes, Silvia F. de Sousa, Josiane A. França, Nubia B. Pereira, Helder A. Pontes, Aline C. Batista, Danyel E. Perez, Ricardo C. Albuquerque, Lelia B. de Souza, Manoela D. Martins, Marina G. Diniz, Ricardo S. Gomez. KRAS mutations drive adenomatoid odontogenic tumor and are independent of clinicopathological features [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4663.

Abstract 1811: The long noncoding RNA KIAA0125 is aberrantly expressed in ameloblastomas

Abstract Long noncoding RNAs (lncRNAs) are transcribed RNA molecules that can interact with DNA or RNA, transcription factors, histones and other chromatin modifying proteins, affecting the expression level of a broad spectrum of genes. Because of their tissue-specific expression characteristics, lncRNAs hold strong promise as novel biomarkers and therapeutic targets for diseases. High-density whole-genome microarray analysis in ameloblastomas, an aggressive odontogenic tumor, and in adenomatoid odontogenic tumor (AOT), an indolent one, showed a high frequency of copy number alteration at chromosome band 14q32.33, which encompasses the lncRNA gene KIAA0125. To understand molecular mechanisms associated with their biological behavior and considering the copy-number gains observed at 14q32.33, we aimed to investigate the expression levels of the lncRNA KIAA0125 in ameloblastomas and in AOTs. The University Ethics Committee approved this study and patients signed informed consent. Thirteen frozen samples were included: five solid/multicystic ameloblastomas, four AOT, and four dental follicles. qPCR reactions were performed in triplicates and the relative changes in gene expression were obtained using the 2^-ΔΔCt formula. The reference gene HPRT1 was used for normalization and the human keratinocyte HaCat cell line was used as calibrator. Differences in the relative changes in gene expression between two groups of samples were assessed and the significance level was set at 0.05. All samples expressed more KIAA0125 than the calibrator. The ameloblastoma group showed higher expression levels of KIAA0125 when compared to dental follicles (p=0.042), while there was no difference between the expression in ameloblastomas and AOT (p&amp;gt;0.05). The expression levels of KIAA0125 in AOT were not different from that of the dental follicle. Our findings suggest that lncRNA KIAA0125 is likely involved in ameloblastoma pathobiology. LncRNAs hold strong promise as therapeutic targets, and experimental validation of this lncRNA functions may lead to tailored therapies targeting KIAA0125 in extensive and recurrent ameloblastomas. Citation Format: Silvia F. Sousa, Marina G. Diniz, Josiane A. França, Fabricio A. Vilas-Boas, Fabricio T. Souza, George A. Calin, Ricardo S. Gomez, Carolina C. Gomes. The long noncoding RNA KIAA0125 is aberrantly expressed in ameloblastomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1811.

IMMUNOHISTOCHEMICAL ANALYSIS OF SOX2, FGF-10 AND WNT-1 IN BENIGN EPITHELIAL ODONTOGENIC LESIONS

Objectives This study evaluated the immunoexpression of SOX2, FGF-10 and Wnt-1 in 20 cases of odontogenic keratocyst (OKC), 20 solid ameloblastoma (AM), 20 adenomatoid odontogenic tumor (AOT), 10 calcifying epithelial odontogenic tumor (CEOT) and 5 dental germs. Findings The analysis of SOX2 immunoexpression revealed positivity in most cases of the lesions. The immunostaining score for SOX2 revealed a statistically significant difference between the groups of lesions, with a higher frequency in OKC and CEOT (p Conclusions The expression pattern of SOX2, FGF-10 and Wnt-1 in dental germs and odontogenic lesions evaluated here confirms the participation of these proteins in the tooth development as well as in the development of benign epithelial odontogenic lesions.