Primordial odontogenic tumor: An immunohistochemical profile.

BACKGROUND: Primordial Odontogenic Tumor (POT) is a recently described odontogenic tumor characterized by a variably cellular loose fibrous tissue with areas similar to the dental papilla, covered by cuboidal to columnar epithelium that resembles the internal epithelium of the enamel organ, surrounded at least partly by a delicate fibrous capsule. The purpose of this study was to investigate the possible histogenesis and biological behavior of this rare tumor by means of a wide immunohistochemical analysis of its epithelial and mesenchymal components. MATERIAL AND METHODS: The immunoexpression of twenty-three different antibodies were evaluated in four cases of POT. RESULTS: The epithelial cells that cover the periphery of the tumor showed immunopositivity for Cytokeratins 14 and 19, while Amelogenin, Glut-1, MOC-31, Caveolin-1. Galectin-3, PITX2, p53, Bax, Bcl-2, Survivin and PTEN were variably expressed in focal areas. The mesenchymal component of the tumor was positive for Vimentin, Syndecan-1, PITX2, Endoglin (CD105), CD 34, Cyclin D1, Bax, Bcl-2, Survivin and p53. PTEN and CD 90 showed a moderate positivity. BRAF V600E and Calretinin were negative in all samples. Cell proliferation markers (Ki-67, MCM-7) were expressed in <5% of the tumor cells. CONCLUSIONS: According to these immunohistochemical findings, we may conclude that POT is a benign odontogenic tumor in which there is both epithelial and mesenchymal activity during its histogenesis, as there is expression of certain components in particular zones in both tissues that suggests this tumor develops during the immature (primordial) stage of tooth development, leading to its inclusion within the group of benign mixed epithelial and mesenchymal odontogenic tumours in the current World Health Organization classification of these lesions.

Comparative histological and immunohistochemical study of ameloblastomas and ameloblastic carcinomas.

BACKGROUND: This study aimed to compare the histological and immunohistochemical characteristics of ameloblastomas (AM) and ameloblastic carcinomas (AC). MATERIAL AND METHODS: Fifteen cases of AM and 9 AC were submitted to hematoxilin and eosin (H&E) and immunohistochemical analysis with the following antibodies: cytokeratins 5,7,8,14 and 19, Ki-67, p53, p63 and the cellular adhesion molecules CD138 (Syndecan-1), E-cadherin and ß-catenin. The mean score of the expression of Ki-67 and p53 labelling index (LIs) were compared between the groups using the t test. A value of p<0.05 was considered to be statistically significant. RESULTS: All cases were positive for CKs 5, 14 and 19, but negative for CKs 7 and 8. CKs 5 and 19 were positive mainly in the central regions of the ameloblastic islands, while the expression in AC was variable in intensity and localization. CK14 was also variably expressed in both AM and AC. Ki-67 (P=.001) and p53 (P=.004) immunoexpression was higher in AC. All cases were positive for p63, but values were higher in AC. CD138 was mainly expressed in peripheral cells of AM, with a weak positivity in the central areas, while it was positive in most areas of ACs, except in less differentiated regions, where expression was decreased or lost. E-cadherin and ß-catenin were weakly positive in both AM and AC. CONCLUSIONS: These results shows that Ki-67, p53 and p63 expression was higher in AC as compared to AM, suggesting that these markers can be useful when considering diagnosis of malignancy, and perhaps could play a role in malignant transformation of AM. Pattern of expression of CKs 5 and 19 in AC were different to those found in AM, suggesting genetic alterations of these proteins in malignant cells. It was confirmed that CK19 is a good marker for benign odontogenic tumors, such as AM, but it is variably expressed in malignant cases.

ESEM Detection of Foreign Metallic Particles inside Ameloblastomatous Cells.

Ameloblastoma is a borderline tumor of odontogenic origin, with a high recurrence rate and possible local aggressiveness. The etiopathogenetic factors involved in its occurrence are not still defined and our study has been precisely aimed to search for novel factors associated with its development. Sections cut from paraffin blocks, containing the representative specimens of 18 different ameloblastomas, collected in a 15-year period (1999-2014), have been observed by an environmental scanning electron microscope, in order to search micro- and nano-sized particles and to identify their composition. In all the neoplastic cases, micro- and nano-sized metallic debris, differing in size and composition, have been detected inside the ameloblastomatous cells. On the contrary, the total absence of metallic particles in the healthy control cases has been emerged. Our results reveal a relationship between ameloblastoma and metallic particulate. The cigarette smoke and the routine dental practice appear the most probable source for the presence of these biopersistant inorganic particles inside the neoplastic cells.

Immunohistochemical characteristics of cystic odontogenic lesions: a comparative study.

OBJECTIVE: Cystic ameloblastoma, keratocystic odontogenic tumor, dentigerous cyst, and radicular cyst are the most commonly encountered cystic odontogenic lesions. The aim of this study was to investigate the expressions of survivin, E-cadherin, CD138, and CD38 in these lesions and their potential diagnostic usage. MATERIAL AND METHOD: A total of 20 cases, consisting 5 radicular cysts, 5 dentigerous cysts, 5 keratocystic odontogenic tumors and 5 cystic ameloblastomas were included in our series. For all cases, sections from the selected blocks were stained against the antibodies for survivin, E-cadherin, CD138, and CD38 on an automated device. RESULTS: All cystic ameloblastomas and keratocystic odontogenic tumors showed diffuse and strong nuclear survivin expression. No specific survivin immunoreactivity was observed in the dentigerous and radicular cysts. E-cadherin expression was stronger in all dentigerous cysts and radicular cysts when compared to others. CD138 expression in stromal cells was prominent in cystic ameloblastomas, but gradually decreased in the other three lesions. All cases were negative for CD38. CONCLUSION: In the present study, loss of E-cadherin expression in epithelial cells, strong CD138 expression in stromal cells and strong nuclear survivin expression both in epithelial and stromal cells in cystic ameloblastomas and keratocystic odontogenic tumors were the most remarkable findings. These findings are also reinforced by the studies suggesting their role in the aggressiveness and pathogenesis of these tumors.

Expression of CD34 and maspin in ameloblastoma from a West African subpopulation.

Ameloblastoma is a locally invasive odontogenic tumor with a high recurrence rate. Its local invasiveness is aided by angiogenesis, which can be correctly estimated by CD34. On the other hand, maspin decreases the local invasive and metastatic capability of cancer cells and functions as an angiogenesis inhibitor. We aim to assess the association between maspin expression and microvessel density in ameloblastoma. Twenty-five formalin-fixed paraffin-embedded (FFPE) blocks of ameloblastoma cases were prepared for antibody processing to CD34 and maspin. Positive immunohistochemical staining was marked by brown cytoplasmic/membrane coloration for CD34 and by nuclear/cytoplasmic coloration for maspin. At the ×40 magnification, we counted blood vessels in two areas of dimension; 300 × 400 µm (area A) and 150 × 200 µm (area B) adjacent to the tumor region to assess relative dispersion of the vessels bordering the tumor. The overall approximate microvessel density (MVD) for area A = 11 (minimum 2, maximum 21) and that for area B = 5 (minimum 1, maximum 10). The MVD in the area A of plexiform ameloblastoma was similar to that of the unicystic, while the hemangiomatous variant had the highest MVD for area A. Maspin positivity was present only in the cytoplasm of ameloblast, stellate reticulum, and the fibrous connective tissue in varying proportions. There was no evidence of the anti-angiogenesis effect of maspin in ameloblastoma from this study. The significance of cytoplasmic localization of maspin in the ameloblasts and stellate reticulum cells needs further investigation.

Odontogenic keratocysts/keratocystic odontogenic tumours: biological characteristics, clinical manifestation and treatment.

BACKGROUND: Odontogenic keratocysts (OKCs) now reclassified as Keratocystic odontogenic tumours (KCOTs) are a clinical entity with a characteristic microscopic picture, kinetic growth and biological behaviour. They arise from the proliferation of the epithelial dental lamina in both maxilla and mandible and occur in patients of all ages. 70-80% of keratocysts are found in the mandible commonly in the angle between the jaw and mandibular branch and maxillary region of the third molar. The cysts are long latent, often symptomless and may attain remarkable dimensions without significant deformation of the jaw bones. They are often found during routine dental X-ray examination. Compared to other types of jaw cyst, odontogenic cysts have a striking tendency to rapid growth and re-occurrence. AIMS: This review focuses on the biological characteristics, clinical behaviour and treatment of KCOTs. METHODS: The databases searched were the PubMed interface of MEDLINE and LILACS. RESULTS AND CONCLUSIONS: Ondontogenic keratinocysts are not currently a diagnostic problem. Orthopantomograms which are today ordinary tools of dental investigation enable diagnosis of clinically asymptomatic cystic lesions. The problem remains the optimal therapeutic approach to reduce the still high likelihood of postoperative recurrence. There is no complete consensus on the ideal operating procedure but cystectomy with delayed extirpation is favoured. An open question also remains the timeliness of screening for postoperative recurrences. Given that the first clinical manifestation of Nevoid Basal Cell Carcioma Syndome (NBCCS) may be lesions of this type, routine histopathological classification supplemented by analysis of immunophenotype should be done. Patients with proven sporadic and especially syndromic OKC should be long term screened. In patients with NBCC preventive X ray examination is recommended only once a year.

Differential expression of transcription factors Snail, Slug, SIP1, and Twist in ameloblastoma.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) via the mechanism of transcription repression is a crucial process for the induction of invasiveness in many human tumors. Ameloblastoma is a benign odontogenic epithelial neoplasm with a locally infiltrative behavior. Twist, an EMT promoter, has been implicated in its invasiveness. The roles of the other transcription factors remain unclarified. MATERIALS AND METHODS: Four transcription factors, namely Snail, Slug, SIP1, and Twist, were examined immunohistochemically in 64 ameloblastoma [18 unicystic (UA), 20 solid/multicystic (SA), 4 desmoplastic (DA), and 22 recurrent (RA)]. RESULTS: All four transcription factors were differentially expressed in ameloblastoma [Snail: n = 60/64 (94%); Slug: n = 21/64 (33%); SIP: n = 18/64 (28%); Twist: n = 26/64 (41%)] (P < 0.05). Their distribution patterns were heterogeneous and were not significantly different between the tumor invasive front and central area (P > 0.05). Intracellular protein localization was predominantly nuclear for Snail, cytoplasmic>nuclear for Slug and SIP1, and cytoplasmic/nuclear for Twist. Overexpression of Snail in most subsets (UA = 18/18; SMA = 19/20; DA = 4/4; RA = 19/22) compared with the other transcription factors (P < 0.05) and selective expression for Slug, SIP1, and Twist in squamous/keratinous foci and at sites of epithelial cystic degeneration were among the main observations made. Stromal cells surrounding immunoreactive tumor cells tended to stain positive. CONCLUSIONS: Present findings suggest that these transcription factors probably play differential roles in mediating local invasiveness in ameloblastoma. Overexpression of Snail in most subsets suggests that this molecule is most likely the prototype transcription factor involved in inducing EMT in the ameloblastoma.

[Primary intra-osseous carcinoma]. / Carcinoma primario intraóseo.

Primary intra-osseous carcinoma (PIOC) is a rare tumor, defined as squamous cell carcinoma that develops in the jaw bones, having no initial connection to adjacent skin or mucosa. It is locally aggressive, with metastases to regional lymph nodes, (28% of cases) and lung (5% of cases) at the time of diagnosis. Its origin may be di novo or from other odontogenic tumors. The maxillary bones have epithelial tissues; therefore this neoplasm is located exclusively on this site, predominantly in the jaw. PIOC diagnostic criteria are strict and include: squamous cell carcinoma histopathology, lack of commitment and sinus mucosa, ruling out the possibility of metastasis from a distant site with a thorough clinical study and complementary methods. The treatment is, whenever possible, oncologic resection, additional radio and / or chemotherapy. Reconstructive surgery with graft and / or prostheses for aesthetic and functional are also required. We report the case of a 72 years old man who consulted for sore jaw three months after molar extraction. Curettage biopsy was performed and then resected mandible with lymphadenectomy. Histopathological examination showed a poorly differentiated squamous cell carcinoma, infiltrating jawbone with morphological findings linking him to residual odontogenic cyst and metastatic lymph nodes in 15 of 48 isolates. Postoperative radiotherapy was performed, he died at 30 months of diagnosis by progressive deterioration.

Carcinoma primario intraóseo / Primary intra-osseous carcinoma

El carcinoma primario intraóseo (PIOC) es un tumor poco frecuente, definido como carcinoma escamoso que se desarrolla en huesos maxilares, no teniendo conexión inicial con mucosa ni piel adyacente. Es localmente agresivo, con una incidencia de metástasis en ganglios regionales del 28% y en pulmón del 5%, en el momento del diagnóstico. Su origen puede ser de novo o a partir de otros tumores odontogénicos. Los huesos maxilares son los únicos que tienen en su interior tejidos epiteliales, por lo cual esta neoplasia se localiza exclusivamente en este sitio, predominantemente en la mandíbula. Los criterios diagnósticos del PIOC incluyen: histopatología de carcinoma escamocelular, ausencia de compromiso de mucosa oral y senos paranasales, descartando metástasis de un sitio distante en base a estudios clínicos y métodos complementarios. El tratamiento de elección consiste, siempre que sea posible, en la exéresis con criterios oncológicos, y radio y/o quimioterapia adicional. Se requiere además, cirugía reconstructiva con injerto y/o prótesis con fines estéticos y funcionales. Presentamos el caso de un varón de 72 años, que consultó por molestias en maxilar inferior tres meses después de la extracción de un molar. Se efectuó biopsia por curetaje y luego se resecó el maxilar inferior con vaciamiento ganglionar. El estudio histopatológico mostró un carcinoma escamoso pobremente diferenciado, infiltrante en hueso maxilar, con hallazgos morfológicos que lo vinculaban a quiste odontogénico residual, y metástasis en 15 de 48 ganglios aislados. Se realizó radioterapia postquirúrgica, falleciendo a los 30 meses del diagnóstico por deterioro progresivo.

Primary intra-osseous carcinoma (PIOC) is a rare tumor, defined as squamous cell carcinoma that develops in the jaw bones, having no initial connection to adjacent skin or mucosa. It is locally aggressive, with metastases to regional lymph nodes, (28% of cases) and lung (5% of cases) at the time of diagnosis. Its origin may be di novo or from other odontogenic tumors. The maxillary bones have epithelial tissues; therefore this neoplasm is located exclusively on this site, predominantly in the jaw. PIOC diagnostic criteria are strict and include: squamous cell carcinoma histopathology, lack of commitment and sinus mucosa, ruling out the possibility of metastasis from a distant site with a thorough clinical study and complementary methods. The treatment is, whenever possible, oncologic resection, additional radio and / or chemotherapy. Reconstructive surgery with graft and / or prostheses for aesthetic and functional are also required. We report the case of a 72 years old man who consulted for sore jaw three months after molar extraction. Curettage biopsy was performed and then resected mandible with lymphadenectomy. Histopathological examination showed a poorly differentiated squamous cell carcinoma, infiltrating jawbone with morphological findings linking him to residual odontogenic cyst and metastatic lymph nodes in 15 of 48 isolates. Postoperative radiotherapy was performed, he died at 30 months of diagnosis by progressive deterioration.

LINE-1 methylation difference between ameloblastoma and keratocystic odontogenic tumor.

OBJECTIVE: Global hypomethylation is a common epigenetic event in cancer. Keratocystic odontogenic tumor (KCOT) and ameloblastoma are different tumors but posses the same tissue in origin. Here, we investigated long interspersed nuclear element-1 (LINE-1 or L1) methylation status between ameloblastoma and KCOT. MATERIALS AND METHODS: We studied the methylation levels of the long interspersed nucleotide element-1 (LINE-1) in ameloblastoma and KCOT. After collecting ameloblastoma cells and epithelium lining cells of KCOT by laser capture microdissection from paraffin embedded tissue, combined bisulfite restriction analysis of LINE-1 (COBRALINE-1) was performed to measure LINE-1 methylation levels. RESULTS: The LINE-1 methylation level in KCOT (53.16 +/- 12.03%) was higher than that in ameloblastoma (36.90 +/- 16.52%), with a statistical significance of P = 0.001. The ranges of LINE-1 methylation of both lesions were not associated with either age or sex. CONCLUSION: We found LINE-1 hypomethylation levels between ameloblastoma and KCOT are different. Therefore, global methylations between these tumors are processed differently.

Expression of bone resorption regulators (RANK, RANKL, and OPG) in odontogenic tumors.

OBJECTIVE: To investigate the expression of bone resorption regulators (receptor activator of nuclear factor kappa B [RANK], RANK ligand [RANKL], and osteoprotegerin [OPG]) in calcifying cystic odontogenic tumor (CCOT), adenomatoid odontogenic tumor (AOT), calcifying epithelial odontogenic tumor (CEOT), odontogenic myxoma (OM), and ameloblastic fibroma (AF). STUDY DESIGN: The expression of these mediators was evaluated by means of immunohistochemistry. RESULTS: All specimens demonstrated positive immunoreactivity to RANK, RANKL, and OPG. The quantification of these mediators in epithelium revealed a similar pattern of expression for RANKL and OPG in CCOT, AOT, CEOT, and AF. With regard to stromal/mesenchymal cells, the majority of AOT and CCOT cases showed a higher content of OPG than RANKL, whereas CEOT, OM, and especially AF had a tendency to present a greater content of RANKL than OPG. CONCLUSION: Our data indicate that the CCOT, AOT, CEOT, OM, and AF cell constituents express key regulators of bone metabolism that might locally modulate tumor-associated bone resorption.

Perlecan-rich epithelial linings as a background of proliferative potentials of keratocystic odontogenic tumor.

BACKGROUND: The intraepithelial deposit of perlecan, a basement membrane-type heparan sulfate (HS) proteoglycan, has been demonstrated in neoplastic conditions such as salivary gland tumors, odontogenic tumors, and oral carcinoma in situ. Our aim was to determine whether perlecan turnover was enhanced in the lining cells of keratocystic odontogenic tumor (KCOT), which had been recently renamed from odontogenic keratocyst because of its accumulated evidence of neoplasm, as a possible background for neoplastic proliferation. METHODS: Ten surgical specimens from each of KCOT, dentigerous cyst, and radicular cyst were examined for the expressions of perlecan core protein, HS chains, heparanase, and Ki-67 by immunohistochemistry and in situ hybridization. RESULTS: In KCOT, perlecan core protein and HS chains were localized on the cell border from the parabasal to subkeratinized layers of the lining epithelium. Heparanase was localized in a similar fashion to those for perlecan and HS chains but was within the cytoplasm. mRNA signals for perlecan core protein and heparanase were mostly compatible with their protein signals. Ki-67-positive cells were localized mainly in the second basal cell layers with definitely higher labeling indices (approximately 31.3%, second layer). In contrast to KCOT, dentigerous cysts and radicular cysts had no perlecan, HS chains, and heparanase deposition in their linings with extremely lower Ki-67 indices (0.4-0.8%). CONCLUSION: The result suggests that the characteristic intra-lining-epithelial deposit of perlecan in KCOT, which has never been seen in other cystic jaw lesions, is a new evidence supporting the neoplastic nature of KCOT.

Detection of Notch signaling molecules in ameloblastomas.

BACKGROUND: To evaluate the roles of Notch signaling in the oncogenesis and cytodifferentiation of odontogenic tumors, expression of Notch receptors and ligands was analyzed in ameloblastomas as well as in tooth germs. METHODS: Tissue specimens of nine tooth germs and 32 ameloblastomas were examined by reverse transcriptase polymerase chain reaction and by in situ hybridization to determine the expression of Notch1, Notch2, Notch3, Delta1, and Jagged1. RESULTS: mRNA expression of Notch1, Notch2, Notch3, Delta1, and Jagged1 was detected in all samples of normal and neoplastic odontogenic tissues. In tooth germs, Notch receptors were expressed in odontogenic epithelium (except for inner enamel epithelium), and expression of Notch ligands was lower in inner enamel epithelium than in other epithelial components. Odontogenic mesenchymal components were weakly reactive with these Notch signaling molecules. Ameloblastomas showed expression of Notch receptors and ligands in central polyhedral neoplastic cells. Notch2, Delta1, and Jagged1 were expressed in some neoplastic cells neighboring the basement membrane. Expression of Notch receptors and ligands was not found in keratinizing cells or granular cells in ameloblastoma variants. Stromal cells were weakly reactive with these Notch signaling molecules. CONCLUSION: Expression of Notch receptors and ligands in tooth germs and ameloblastomas suggests that Notch signaling might control cell differentiation and proliferation of normal and neoplastic odontogenic epithelium.

Perivascular myoid tumors of the oral region: a clinicopathologic re-evaluation of 35 cases.

BACKGROUND: Myopericytoma (MPC) is a generic denomination to describe tumors showing differentiation toward perivascular myoid cells /myopericytes. It has been suggested that MPC forms a morphologic continuum with glomus tumor (GT), solitary myofibroma (SMF), and angioleiomyoma (ALM). This proposed relationship has not yet been assessed in the oral region. METHODS: We reviewed our 28-year experience with 35 oral tumors, originally diagnosed as ALM (n = 28), SMF (n = 4), GT (n = 2), and MPC (n = 1) to analyze their overlapping microscopic features, with the assistance of immunohistochemistry. RESULTS: Myopericytoma showed a wide range of growth patterns; concentric perivascular whorls, hemangiopericytomatous areas, glomangiopericytoma (GPC)-type vessels and leiomyomatous foci. Intravascular growth was also seen. Among 28 cases studied, three ALM were reclassified as MPC (n = 2) and SMF (n = 1), based on the present diagnostic criteria. Additional MPC-type components, at varying degrees, were similarly found in four ALM and three SMF, at least focally. One GT featured intravascular whorls of spindle cells. These four interrelated groups of tumors had in common GPC-type vasculature and intraluminal cellular proliferation was nearly ubiquitously present. Diffuse immunoreactivity for alpha-smooth muscle actin and less staining intensity of muscle-specific actin were observed in all tumors. Only ALM displayed desmin positivity of variable extent. Neither case tested expressed CD34. CONCLUSIONS: Our data matches with the recent results in extraoral sites that MPC, GT, SMF, and ALM exhibit histologic and immunohistochemical overlap with each other. A common perivascular myoid differentiation between these tumor types is further reinforced by the present oral series.

Ultrastructural studies of jaw lymphomas and apoptosis.

Research on ultrastructural cytopathological changes and apoptosis that occur in jaw lymphoma were done by using electron microscopy and ground sections. The author described this tumor in 1977-1978 as a highly malignant and lethal condition affecting children between 2 and 8 years (mean age 5 years). A duration of illness between 2 and 3 weeks is common and with a general condition of severe toxicity, anemia, and high body temperature. Clinical and pathological features of 24 children with jaw lymphoma seen in the Maxillofacial Unit, Surgical Specialized Hospital, Medical city, Baghdad, are described. Thirteen males and 11 females were included, with a death rate at 91.1%. The morphological characteristics were examined by ground sections. Lymphoblastic lymphoma features were observed and apoptotic changes were seen in some of the cells. Electron microscopy showed a high number of mitotic figures and lymphoblast transformation to plasma cells with high nucleo-cytoplasmic ratio. Some cells had double nuclei and some nuclei were more convoluted. Apoptotic changes were seen in some cells; chromatin clumps aggregated near the nuclear membrane. Cytoplasmic processes and mitochondria showing degeneration and virus-like particles were seen in both nuclei and cytoplasm. The presence of a high mitotic figure with active oncogenic virus growth and reduced apoptosis is a poor prognostic feature in jaw lymphoma.

A immunohistochemical study of the peripheral ameloblastoma.

AIM: Peripheral ameloblastoma (PA) is a rare variant of ameloblastoma occurring in the extraosseous region. With regard to the histogenesis of the tumor, two major sources of origin are considered: odontogenic epithelial remnants and the gingival epithelium. In this study, we examined the immunohistochemical profiles of cytokeratins (CKs) and Ki-67 labeling index (LI) of PAs, and discuss the histogenesis and the biologic behavior of the PA. MATERIALS AND METHODS: Eight cases of PA were retrieved from the pathology files of 212 cases of ameloblastoma that had been registered at our hospital. Immunohistochemical staining was performed in seven cases using monoclonal antibodies of six CKs (7, 8, 13, 14, 18, and 19) and Ki-67. RESULTS: All cases of PA expressed CK13, 14, and 19. CK18 was positive staining in six cases, and CK8 in five cases. This staining pattern was similar to that in intraosseous ameloblastomas (IAs). The mean of Ki-67 LI of PAs (1.91%) was significantly lower than that of IAs (4.82%) (P = 0.002). CONCLUSION: We consider that the PA originates from odontogenic epithelial remnants rather than from the gingival epithelium, and the Ki-67 LI of the tumor is a good prognostic indicator.

Immunohistochemical detection of phosphorylated Akt, PI3K, and PTEN in ameloblastic tumors.

OBJECTIVE: To evaluate roles of the Akt signaling pathway in oncogenesis and cytodifferentiation of odontogenic tumors, expression of phosphorylated Akt (pAkt), PI3K, and PTEN was analyzed in ameloblastic tumors as well as in tooth germs. METHODS: 11 tooth germs, 40 ameloblastomas, and 5 malignant ameloblastic tumors were examined immunohistochemically with antibodies against pAkt, PI3K, and PTEN. RESULTS: Immunoreactivity for pAkt, PI3K, and PTEN was detected predominantly in odontogenic epithelial cells near the basement membrane in tooth germs and ameloblastic tumors. The levels of immunoreactivity for pAkt and PI3K were slightly higher in ameloblastic tumors than in tooth germs. Plexiform ameloblastomas showed significantly higher expression of PI3K than follicular ameloblastomas, and PI3K immunoreactivity in ameloblastomas without cellular variation was significantly higher than that in acanthomatous ameloblastomas. The level of PTEN immunoreactivity was significantly lower in ameloblastomas than in tooth germs. CONCLUSION: Expression of pAkt, PI3K, and PTEN in tooth germs and ameloblastic tumors suggests that these signaling molecules regulate cell survival and growth in normal and neoplastic odontogenic tissues by mediating growth factor signals. Increased expression of pAkt and PI3K and decreased expression of PTEN in ameloblastic tumors may participate in oncogenesis of odontogenic epithelium by activating the Akt signaling pathway.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Quantitative analysis of argyrophilic nucleolar organizer regions and epidermal growth factor receptor in ameloblastomas.

OBJECTIVE: The aim of this study was to evaluate the proliferation activity by means of the quantification of the argyrophilic nucleolar organizer regions (AgNORs) and the patterns of expression of the epidermal growth factor receptor (EGFR) in ameloblastomas. METHOD: The methods of evaluation included the H/E stain for the morphologic analysis, the silver impregnation technique for quantification of the AgNORs and the immunohistochemical stain with anti-EGFR antibody in 11 cases of ameloblastoma. RESULTS: The results did not show a significant statistical difference as per quantification of the AgNORs. The expression of the EGFR on the epithelial islands of ameloblastoma was not uniform, and the location of the expression was also variable. The predominant expression was that of cytoplasm and the islands with an expression of membrane only were rare and generally smaller in size. CONCLUSION: The tumor presents an irregular growth. Smaller islands are associated with a higher proliferation activity and therefore could be responsible for tumor infiltration.