Desmoplastic Ameloblastomas Research Articles

EPIDEMIOLOGICAL ASPECTS OF AMELOBLASTOMAS IN A SOUTHEAST BRAZILIAN POPULATION

This study aimed to describe the epidemiological aspects of ameloblastomas (AME) in a Southeast Brazilian population. Sociodemographic and clinical-pathological data were gathered from the archives of two Oral Pathology Services. A total of 111 cases were diagnosed as AME (0.57% of all records). Of these, 90 cases were classified as solid/multicystic (81.1%), 18 as unicystic (16.2%), 2 as peripheral (1.8%), and 1 as desmoplastic AME (0.9%). These lesions showed a slight predilection for male (54.1%) and afro-descendant (59.6%) patients, with a mean age of 35.8 ±19.5. The mandible was the main affected area (93.7%), with a mean size of 5.2 ±2.7. Long-lasting, asymptomatic swelling was the generally cited complaint. Pain was reported in only 17.1% of the cases. Most case were radiographically described as multilocular, well-defined, radiolucencies. In this sample, AME depicted similar clinical-pathological features, when compared with most of the previously published studies (Support: PAPE-UNIUBE/ FAPEMIG APQ-03179-18). This study aimed to describe the epidemiological aspects of ameloblastomas (AME) in a Southeast Brazilian population. Sociodemographic and clinical-pathological data were gathered from the archives of two Oral Pathology Services. A total of 111 cases were diagnosed as AME (0.57% of all records). Of these, 90 cases were classified as solid/multicystic (81.1%), 18 as unicystic (16.2%), 2 as peripheral (1.8%), and 1 as desmoplastic AME (0.9%). These lesions showed a slight predilection for male (54.1%) and afro-descendant (59.6%) patients, with a mean age of 35.8 ±19.5. The mandible was the main affected area (93.7%), with a mean size of 5.2 ±2.7. Long-lasting, asymptomatic swelling was the generally cited complaint. Pain was reported in only 17.1% of the cases. Most case were radiographically described as multilocular, well-defined, radiolucencies. In this sample, AME depicted similar clinical-pathological features, when compared with most of the previously published studies (Support: PAPE-UNIUBE/ FAPEMIG APQ-03179-18).

Desmoplastic Ameloblastoma: A Case-Series of Three Cases

The desmoplastic ameloblastoma is an uncommon subtype of ameloblastoma. Clinical and radiographic presentation differs from other forms of ameloblastoma, and the lesion is sometimes confused with fibro-osseous lesions, making it important for clinicians to review its distinctive clinical and radiographic features. The authors in this article present three cases of desmoplastic ameloblastomas, which were treated at the Augusta University Oral and Maxillofacial Surgery clinic.

Computed tomographic features of desmoplastic ameloblastoma of the jaw

Objective To retrospectively analyze the clinical and CT imaging features of desmoplastic ameloblastomas (DA) in comparison with other types of ameloblastomas. Methods Patients diagnosed with ameloblastoma histopathologically in Peking University School and Hospital of Stomatology from July 2000 to August 2017 were reviewed to analyze the constituent ratios and characteristics of DA. CT imaging features of DA (28 cases) were investigated in comparison with consecutive cases of solid/multicystic and unicystic ameloblastomas. The following imaging perspectives were analyzed: the border, internal structure, three-dimensional shape, tooth, the periodontium, the cortex and the expansion of the tumors. CT values were measured in the region of interest for quantitative analysis. Results Among the 1 269 cases of ameloblastomas, 50 (3.9%) were DA, which showed predilections for males (74.0%). The average age of DA was about 43.9 years old, which was higher than the other two types. The anterior incisorcanine region (62.0%) and premolar region (30.0%) were most frequently affected. The incidence rate of DA in mandibule was 56.0% (28/50), which was slightly higher than that of maxilla (44.0%). The DA characteristically showed scallop border and honeycomblike or soapbubble internal structure with bone formation on CT. The mean ratios of height to mesiodistal and buccal-lingual to mesio-distal distances were 0.76 and 0.63, which were higher than the other two types. According to the degree of internal bone formation, three subtypes of DA could be observed: densely ossifying type (I), honeycomb/soap bubble type (II) and sparsely ossifying type (III). The means and standard deviations of CT values of DA were significantly higher than those of the other two types, which were (488.8±164.0) HU (type I), (171.7±102.8) HU (type II), (42.1±8.8) HU (type III). Conclusion CT is helpful for diagnosis of DA, which shows as solid tumor with varying degrees of internal ossification.

Immunohistochemical Expression of Myofibroblasts Using Alpha-smooth Muscle Actin (SMA) to Assess the Aggressive Potential of Various Clinical Subtypes of Ameloblastoma.

Objective:Ameloblastoma is a rare odontogenic neoplasm with high recurrence rates if improperly treated. If left untreated (or is treated inadequately), it can cause substantial morbidity, disfigurement, and even death. Hence, there is a need to explore the stromal cells too, which might play an important role in assessing its aggressive behavior and may help to predict the recurrence of different clinical variants of ameloblastoma. Myofibroblasts (MFs) are such cells which have been studied in various lesions.Materials and Methods:This retrospective study involved archival tissues of ameloblastoma. Among a total of 40 cases, 12 cases of SMA (solid multicystic ameloblastoma), 10 cases of unicystic ameloblastoma (UA), 8 cases of desmoplastic ameloblastoma, and 10 cases of oral squamous cell carcinoma were selected as control. Immunohistochemical staining with anti-alpha-smooth muscle actin antibody was done. Interpretation of ten examined fields was counted by three observers.Results:Significant difference in the number of MFs in SMA and UA and desmoplastic ameloblastoma and UA (P < 0.05) was found. However, there was no statistically significant difference in MFs of SMA and desmoplastic ameloblastomas (P > 0.05). In addition, there was no statistically significant difference in the staining intensity between the three variants (P > 0.05).Conclusion:A significant correlation was obtained between the number of MF in all the three clinical variants, i.e., SMA, UA, and desmoplastic ameloblastoma (P = 0.02), which is the unique feature of the study.

Quantitative evaluation of microvessel density using CD34 in clinical variants of ameloblastoma: An immunohistochemical study.

Background:Odontogenic epithelium plays an important role in the histogenesis of odontogenic tumors of the jaws. Ameloblastomas, which arise from odontogenic epithelium, are considered benign with little tendency to metastasize. Tumors require an adequate supply of oxygen and a way to remove their waste products. This can be achieved by angiogenesis. In situ quantification of the microvessel density (MVD) is a usual method for assessing angiogenesis. Moreover, angiogenesis may differ in subtypes of ameloblastomas and could play a role in determining the pattern of tumor growth.Aim:The aim of the present study was to demonstrate the expression of cluster of differentiation (CD34) in variants of ameloblastomas and to correlate and compare their expression to the aggressive behavior.Materials and Methods:A retrospective cross-sectional study which included forty paraffin blocks was conducted after obtaining ethical committee clearance. Ten cases of pyogenic granuloma were used as a positive control and thirty cases were of solid multicystic ameloblastoma (SMA), unicystic ameloblastoma (UA) and desmoplastic ameloblastomas. Angiogenesis was assessed using CD34 antigen and was immunohistochemically localized. Statistical analysis was carried out for comparative analysis with the help of ANOVA test, Kolmogorov–Smirnov test and least significance difference test.Results:A significant correlation was obtained between the MVD of all the three variants, i.e., SMA, UA and desmoplastic ameloblastomas which was statistically significant (P < 0.05).Conclusion:Increased MVD in the three variants, i.e., SMA, UA and desmoplastic ameloblastoma seen in the present study could suggest that the angiogenesis has an important role in tumor progression and aggressiveness of ameloblastomas.

Solid ameloblastomas -Retrospective clinical and histopathologic study of 54 cases

SummaryRecently, the World Health Organization (WHO) excluded the desmoplastic pattern from the histopathological spectrum of solid ameloblastomas and classified it as a distinct variant, named desmoplastic ameloblastoma.AimTo perform a retrospective analysis of the clinicopathologic aspects in a case series of solid ameloblastomas.Study designCross-sectional cohort study.Materials and methodsData regarding age, gender, location and clinical characteristics were retrieved from patient records. Histological sections were evaluated regarding existing histological patterns and the predominant histological pattern. Cases were classified according to the study of Waldron and El-Mofty (1987) and the WHO classification of 2005.ResultsA total of 54 cases were identified, with similar gender distribution and a mean age of 38.3 years. Fifty three cases (98.1%) affected the mandible. Forty nine cases (90.8%) were classified as solid ameloblastomas, 3 (5.6%) as desmoplastic ameloblastomas, and 2 (3.7%) as hybrid lesions. The most frequent histological patterns in solid ameloblastomas were follicular (77.6%), acanthomatous (69.4%), and plexiform (65.3%). Focal areas of desmoplastic ameloblastomas were identified in 11 solid ameloblastomas (22.4%).ConclusionDespite its characterization as a distinct variant, our results revealed that focal areas of desmoplastic ameloblastomas can be observed with some frequency in conventional ameloblastomas.

Abstract 702: BRAF V600E mutation in benign and malignant epithelial odontogenic tumors

Abstract The classification of ameloblastoma in multicystic or unicystic variants is associated with its clinical behaviour. Recently, BRAF and SMO mutations have been reported in ameloblastomas. However, it is not clear if such mutations are shared by the multi- and unicystic variants of ameloblastoma or by odontogenic carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin-embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas, were included. The BRAFV600E mutation was assessed by real-time PCR with a specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation was assessed by Sanger sequencing. Fourteen out of 17 (82%) ameloblastomas showed the BRAFV600E mutation, specifically, 5/6 (83%) unicystic, 7/9 (78%) multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected in 4/11 (36%) malignant tumours, specifically, 3/8 (38%) ameloblastic carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E mutation was less frequent in odontogenic carcinomas than in ameloblastomas. In ameloblastomas, this mutation occurred at similar proportions in cases from the mandible and maxilla, as well as among unicystic, multicystic and desmoplastic variants, suggesting that there is no difference in their molecular pathogenesis. Our findings support the possibility for personalised, molecular targeted therapy for ameloblastomas and ameloblastic carcinomas harbouring the BRAFV600E mutation. Supported by: FAPEMIG (Fundação de Amparo à Pesquisa de Minas Gerais), CNPq (National Council for Scientific and Technological Development) and CAPES (Coordination for Improvement of Higher Education Personnel), Brazil Citation Format: Marina Goncalves Diniz, Carolina Cavalieri Gomes, Bruna Viana Antonini Guimaraes, Alessandra Pires Duarte, Ricardo Santiago Gomez. BRAF V600E mutation in benign and malignant epithelial odontogenic tumors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 702. doi:10.1158/1538-7445.AM2015-702

Assessment of BRAFV600E and SMOF412E mutations in epithelial odontogenic tumours.

The classification of ameloblastoma in multicystic or unicystic variants is associated with its clinical behaviour. Recently, BRAF and SMO mutations have been reported in ameloblastomas. However, it is not clear if such mutations are shared by the multi- and unicystic variants of ameloblastoma or by odontogenic carcinomas. We assessed BRAFV600E and SMOF412E in multicystic, unicystic and desmoplastic ameloblastomas. In addition, we investigated whether the BRAFV600E mutation occurs in odontogenic carcinomas. A total of 28 formalin-fixed paraffin-embedded samples, comprising 17 ameloblastomas and 11 odontogenic carcinomas, were included. The BRAFV600E mutation was assessed by real-time PCR with a specific TaqMan probe and confirmed by Sanger sequencing. The SMOF412E mutation was assessed by Sanger sequencing. Fourteen out of 17 (82 %) ameloblastomas showed the BRAFV600E mutation, specifically, 5/6 (83 %) unicystic, 7/9 (78 %) multicystic and 2/2 desmoplastic ameloblastomas. BRAFV600E mutation was detected in 4/11 (36 %) malignant tumours, specifically, 3/8 (38 %) ameloblastic carcinomas and 1/1 clear cell odontogenic carcinoma, while the two ghost cell odontogenic carcinomas did not harbour this mutation. The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E-activating mutation is a common event in ameloblastomas, occurring regardless of site or histological type. This mutation is also detected in odontogenic carcinomas. SMO somatic mutation is a secondary genetic event in the ameloblastoma pathogenesis. Our findings support the possibility for personalised, molecular-targeted therapy for ameloblastomas and odontogenic carcinomas harbouring the BRAFV600E mutation.

Differential expression of glypican-1 in ameloblastoma variants.

Although benign, ameloblastomas are locally invasive and destructive tumors of the jawbones. The glypicans comprise a family of glycosylphosphatidylinositol-anchored proteoglycans that, by virtue of their cell-surface localization and heparin sulfate chain composition, might regulate the response of cells to numerous heparin-binding growth factors, cell adhesion molecules, and extracellular matrix components. The expression of glypican-1 is differentially altered among different types of malignancies, suggesting a possible role in the tumorigenesis and biological behavior of these neoplasms. The aim of this study was to determine the expression of glypican-1 and then hypothesize the possible role that this protein may play in the biological behavior of ameloblastomas. We assessed the presence of glypican-1 by immunohistochemical staining analyses in a series of 80 cases of different types of ameloblastomas. Desmoplastic ameloblastomas exhibited the highest expression of glypican-1 (100%), followed by the peripheral (66%), solid/multicystic (51.2%), and unicystic (47.2%) types, showing statistically significant differences among them (P<0.001). Differences detected in glypican-1 expression among different subtypes of ameloblastomas, could be suggesting a possible association with their different biological behavior.

PP092: Immunohistochemical expression of glypican-1 in the differents types of ameloblastomas

Purpose Although benigns, ameloblastomas (AM) are locally invasive and destructive tumors of the jawbone. The glypicans are a family of (GPI)-anchored proteoglycans that, by virtue of their cell-surface localization and heparin sulfate chain composition, might regulate the responses of cells to numerous heparin-binding growth factors, cell adhesion molecules, and extracellular matrix components. The expression of glypican-1 is differentially altered among different types of malignancies, suggesting a possible role in the tumorigenesis and biological behavior of these neoplasms. The aim of this study was to determine the expression of glypican-1 and then hypothesize the possible role that this protein plays in the biological behavior of ameloblastomas. Materials and methods We assessed the presence of glypican-1 by immunohistochemical staining analyses in a series of 80 cases of different types of ameloblastomas. Results All of the desmoplastic ameloblastomas exhibited the highest expression of glypican-1 (100%), followed by the peripheral (66%), solid/multicystic (51.2%) and unicystic ameloblastomas (47.2%), showing statistically significant differences within the different types of ameloblastomas (p Conclusions Significant differences were detected in glypican-1 expression among the different types of ameloblastomas, suggesting a possible association between glypican-1 expression and differential biological behavior among these neoplasms. Further studies are required to better understand the biological implications of glypican-1 expression in ameloblastomas, as well as the specific functions of glypican-1 in tumor biology.

Comparison of the value of PCNA and Ki-67 as markers of cell proliferation in ameloblastic tumors

Objectives: The aim of this study was to compare among PCNAand Ki-67 as the most reliable immunohistochemical marker for evaluating cell proliferation in ameloblastic tumors. Study Design: Observational, retrospective, and descriptive study of a large series of ameloblastic tumors, composed of 161 ameloblastomas and four ameloblastic carcinomas, to determine and compare PCNA and Ki-67 expression using immunohistochemistry techniques. Results: When analyzing Ki-67 positivity, the desmoplastic ameloblastoma demonstrated a significantly lower proliferation rate (1.9%) compared with the solid/multicystic and unicystic ameloblastomas and ameloblastic carcinomas (p<0.05), whereas the ameloblastic carcinomas displayed a significantly higher rate compared with all of the other ameloblastomas (48.7%) (p<0.05). When analyzing cell proliferation with PCNA, we found significant differences only between the ameloblastic carcinomas (93.3%) and the desmoplastic ameloblastomas (p<0.05). When differences between the immunopositivity for PCNA and Ki-67 were compared, the percentages were higher for PCNA in all types of ameloblastomas and ameloblastic carcinomas. In all cases, the percentages were greater than 80%, whereas the immunopositivity for Ki-67 was significantly lower; for example, the ameloblastic carcinoma expressed the highest positivity and only reached 48.7%, compared to 93.3% when we used PCNA. Conclusions: In the present study, when we used the proliferation cell marker Ki-67, the percentages of positivity were more specific and varied among the different types of ameloblastomas, suggesting that Ki-67 is a more specific marker for the proliferation of ameloblastic tumor cells. Key words:Ameloblastomas, ameloblastic carcinoma, PCNA, Ki-67, cell proliferation markers.

Tumor-associated macrophages and angiogenesis: A statistical correlation that could reflect a critical relationship in ameloblastoma

Neoplasm growth is determined not only by the tumor cells themselves, but also by the tumor microenvironment. Increased densities of macrophages and activation of angiogenesis have been identified as common events in the progression of several neoplasms. Ameloblastoma is one of the most frequent odontogenic tumors and an excellent model for the study of neoplasm progression due to the different clinical variants that it exhibits. Here, by immunohistochemical studies using antibodies against CD68 and CD34, we evaluated the density of macrophages and microvessels associated to 45 paraffin-embedded ameloblastomas. In solid/multicystic ameloblastoma (SMA), we observed significantly higher densities of both macrophages and microvessels than in unicystic (UA) and desmoplastic (DA) ameloblastomas. Likewise, higher densities of macrophages and microvessels were found in UA than in DA. Furthermore, a predominance of intratumoral and peritumoral macrophage infiltrates was seen in SMA, while in UA, both macrophages and microvessels were also detected in the wall of the cysts. In contrast, DA had scant macrophages and microvessels, mainly situated distant from tumoral cells. In addition, a high correlation between macrophage and microvessel densities was observed in the samples (r=0.9623). Our results suggest that these two tumor microenvironmental elements could have an important role during ameloblastoma progression.

Histopathology of ameloblastoma of the jaws; some critical observations based on a 40 years single institution experience

The aim of the present study is to examine all cases of intraosseous benign ameloblastomas treated between 1970 and 2010 in a single institution and to look for a possible correlation between the histopathological aspects and the demographical and clinical parameters, as well as the treatment outcome. The data of a total number of 44 patients were retrieved from the records. Nine patients were excluded because of doubt about the correct diagnosis (8 patients) or because of an extra-osseous presentation (1 patient). No statistically significant differences were found between the histopathological (sub)types of ameloblastomas and the demographical and clinical parameters, nor between the histopathological (sub)types and treatment outcome. Of the 28 patients treated by enucleation, in 17 patients one or more recurrences occurred, with no significant predilection for any histopathological (sub)type, including the unicystic type. There were no significant differences in the recurrence rate after enucleation in patients below and above the age of 20 years either. In six out of 17 patients with a recurrence, the recurrent lesion showed a different histopathological subtype than was encountered in the primary. In two cases a change from solid/multicystic to desmoplastic ameloblastomas was noticed. In conclusion, the current histopathological classification of benign intraosseous ameloblastoma does not seem to have clinical relevance with the possible exception of the luminal unicystic ameloblastoma that has been removed in toto, unfragmented. Since no primary desmoplastic ameloblastomas were encountered in the present study no further comments can be made on this apparently rare entity. Key words: Odontogenic tumours, ameloblastoma, histopathology.

A clinico-pathological comparison between mandibular and maxillary ameloblastomas in Sri Lanka

The aim of this retrospective study was to analyse the relative prevalence and the clinico-pathological characteristics of mandibular and maxillary ameloblastomas in Sri Lanka. Clinico-pathological features of a total of 286 cases of ameloblastomas were analysed. Out of the 286 cases, 87.8% (251/286) of ameloblastomas occurred in the mandible, while 10.8% (31/286) occurred in the maxilla indicating a ratio of 8:1. In the mandible, 54% (136/251), 40% (100/251) and 6% (15/251) of tumours and in the maxilla, 23% (7/31), 48% (15/31) and 29% (9/31) of tumours were solid/multicystic ameloblastomas (SMA), unicystic ameloblastomas (UA) and desmoplastic ameloblastomas (DA) respectively. No gender predilection was observed in mandibular or maxillary ameloblastomas. Most of the lesions were observed in 2nd to 5th decade of life (mean age 33.2 years). No differences between mandibular and maxillary ameloblastomas were observed with reference to overall cellularity and mitotic activity. Solid/multicystic and UAs showed a predilection to posterior region, while DAs were frequently found in the anterior region of both jaws. Twenty-one percentage (60/286) of ameloblastomas presented with recurrences, and 94% (34/36) of these recurrences were observed in cases treated conservatively. In conclusion, mandibular ameloblastomas were more prevalent than maxillary ameloblastomas, while no differences were observed in age or gender distribution between the mandibular and maxillary ameloblastomas. However, higher proportion of DAs and UAs was observed in the maxilla compared with some of the other studies. SMA should be treated with resection to prevent recurrences.

Expression of extracellular matrix proteins in ameloblastomas and adenomatoid odontogenic tumors

This study evaluated the expression of fibronectin, tenascin and type I collagen in ameloblastomas and adenomatoid odontogenic tumors (AOTs) aiming to contribute with the comprehension of the differences in the biological behavior of these tumors. Immunohistochemical technique was performed in 20 cases of ameloblastoma (16 solid and 4 desmoplastic) and in 10 cases of AOT. All tumors presented moderate fibronectin expression in the stroma. Solid ameloblastomas showed intense expression of fibronectin at the epithelial-mesenchymal interface, whereas desmoplastic ameloblastomas revealed no immunoexpression of fibronectin at this site. Ameloblastomas presented stronger immunoreactivity to tenascin than AOTs, especially at the epithelial-mesenchymal interface. AOTs and desmoplastic ameloblastomas showed intense labeling for type I collagen. The patterns of expression of the proteins studied agree with the locally more invasive behavior of ameloblastomas in comparison to AOTs. Our results might suggest a less invasive behavior of desmoplastic ameloblastoma in comparison to solid ameloblastoma.

Comparative expression of syndecan‐1 and Ki‐67 in peripheral and desmoplastic ameloblastomas and ameloblastic carcinoma

The aims of the present study were to examine whether the pattern of syndecan-1 expression correlates with cellular proliferation index in desmoplastic ameloblastomas (DA), peripheral ameloblastomas (PA) and ameloblastic carcinomas (AC), and to compare with that previously reported for solid (SA) and unicystic (UA) variants of ameloblastoma. Immunohistochemistry was performed for syndecan-1 and Ki-67 in seven ameloblastomas (four DA and three PA) and three AC. Expression of syndecan-1 was related to the histological subtype of tumors and, in the case of malignancy, to lower expression levels observed in AC (22.5%) than in PA (47.5%) or DA (77.5%) (P < 0.05). Syndecan-1 expression correlated inversely with Ki-67 proliferative index: the expression was lower in both types of ameloblastomas (1.5% in DA and 6.4% in PA) than in AC (41.2%; P < 0.05). The present results suggest that the decrease in syndecan-1 expression and increase in the Ki-67 index observed in AC is in accordance with its higher aggressiveness as compared to the rare DA and PA. Interestingly, DA had a lower proliferation index as well as the highest levels of syndecan-1 expression. These data suggest that DA differ from the other types of intraosseous ameloblastomas but more studies are necessary to better understand the role of this protein as a marker in the biological behavior of the epithelial odontogenic neoplasms.

Immunohistochemical detection of BH3‐only proteins in ameloblastic tumors

To evaluate expression of BH3-only proteins in odontogenic tumors, expression of Bid, Bim, Bad, Noxa, and Puma was analyzed in ameloblastic tumors as well as in tooth germs. Nine tooth germs, 37 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with antibodies against Bid, Bim, Bad, Noxa, and Puma. Immunohistochemical reactivity for Bid, Bim, Bad, Noxa, and Puma was detected in the cytoplasm of cellular components in normal and neoplastic odontogenic tissues. Expression of these BH3-only proteins was evident in odontogenic epithelial cells near the basement membrane in tooth germs and ameloblastic tumors. Acanthomatous ameloblastomas showed no reactivity for Bid, Bim, Bad, Noxa, or Puma in keratinizing cells, whereas granular cells in granular cell ameloblastomas reacted with these BH3-only proteins. Basal and desmoplastic ameloblastomas and ameloblastic carcinomas showed immunoreactivity for the BH3-only proteins in most neoplastic cells. Expression of Bid, Bim, Bad, Noxa, and Puma in tooth germs and ameloblastic tumors suggests that the BH3-only proteins have a role in apoptotic cell death of normal and neoplastic odontogenic epithelium. Distinctive expression patterns of these BH3-only proteins in ameloblastoma variants suggest that the BH3-only proteins might be involved in tumor cell differentiation of ameloblastomas.

Case report: Desmoplastic ameloblastoma

Ameloblastomas are tumors arising from the odontogenic epithelium.[1] Despite their locally destructive nature, they are considered benign.[2] They are the commonest neoplasms affecting the jaws.[3] The most common types of ameloblastoma are the follicular and plexiform varieties, followed by the acanthomatous and granular cell types. Uncommon variants include desmoplastic, basal cell, clear cell, keratoameloblastoma, and papilliferous keratoameloblastoma. When the desmoplastic type coexists with other types, it is called a ‘hybrid’ ameloblastoma.[4] There are significant anatomic, histopathologic, and radiologic differences between desmoplastic ameloblastomas and the classic type.

Immunohistochemical detection of insulin‐like growth factors, platelet‐derived growth factor, and their receptors in ameloblastic tumors

To evaluate the roles of growth factors in oncogenesis and cytodifferentiation of odontogenic tumors, expression of insulin-like growth factors (IGFs), platelet-derived growth factor (PDGF), and their receptors was analyzed in ameloblastic tumors as well as in tooth germs. Tissue specimens of 10 tooth germs, 47 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with the use of antibodies against IGF-I, IGF-II, IGF-I receptor (IGF-IR), PDGF A-chain, PDGF B-chain, PDGF alpha-receptor, and PDGF beta-receptor. Immunohistochemical reactivity for IGFs, PDGF chains, and their receptors was detected predominantly in odontogenic epithelial cells near the basement membrane in tooth germs and in benign and malignant ameloblastic tumors. The expression levels of IGF-II and PDGF chains were significantly higher in ameloblastic tumors than in tooth germs. Malignant ameloblastic tumors showed higher reactivity for PDGF chains than benign ameloblastomas and higher reactivity for platelet-derived growth factor receptors than tooth germs. The expression levels of PDGF chains were significantly higher in follicular ameloblastomas than in plexiform ameloblastomas. Desmoplastic ameloblastomas showed higher expression of IGFs and IGF-IR when compared with other ameloblastoma subtypes. Expression of IGFs, PDGF, and their receptors in tooth germs and ameloblastic tumors suggests that these growth factor signals contribute to cell proliferation or survival in both normal and neoplastic odontogenic tissues. Expression of these molecules in odontogenic tissues possibly affects interactions with the bone microenvironment during tooth development and intraosseous progression of ameloblastic tumors. Altered expression of the ligands and receptors in ameloblastic tumors may be involved in oncogenesis, malignant potential, and tumor cell differentiation.

Expression of p63 and p73 in ameloblastomas

To clarify the role of p53 homologs in oncogenesis and cytodifferentiation of odontogenic tumors, expression of p63 and p73 was analyzed in ameloblastomas as well as tooth germs. Tissue specimens of nine tooth germs and 48 benign and five malignant ameloblastomas were examined by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) for the expression of p63 and p73. Immunoreactivity for p63 and p73 was evident in epithelial cells neighboring the basement membrane in developing and neoplastic odontogenic tissues. p63 expression in desmoplastic ameloblastomas was significantly higher than in acanthomatous and granular cell ameloblastomas, and ameloblastic carcinomas showed higher p63 expression than metastasizing ameloblastomas. p73 expression was significantly higher in plexiform ameloblastomas than in follicular ameloblastomas, and basal cell ameloblastomas showed higher p73 expression than granular cell ameloblastomas. mRNA transcripts for Delta Np63 and TAp73 were detected in all developing and neoplastic odontogenic tissues. TAp63 mRNA was expressed in five of eight tooth germs, 16 of 34 ameloblastomas, and one of one malignant ameloblastoma, whereas Delta Np73 mRNA was recognized in one of eight tooth germs, nine of 34 ameloblastomas, and one of one malignant ameloblastoma. The expression of p63 and p73 suggests that these p53 homologs play a role in differentiation and proliferation of odontogenic epithelial cells. Variations of predominantly expressed isoforms suggest that p63 and p73 might differentially function in odontogenic tissues.