共查询到20条相似文献,搜索用时 31 毫秒
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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. 相似文献
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BACKGROUND: To evaluate the roles of angiogenic factors in the development and progression of odontogenic tumors, expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP) and of angiopoietins in ameloblastic tumors as well as in tooth germs. METHODS: Tissue specimens of 11 tooth germs, 44 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with the use of antibodies against PD-ECGF/TP and angiopoietin-1 and -2. RESULTS: Immunohistochemical reactivity for PD-ECGF/TP was detected in mesenchymal cells in tooth germs and stromal cells in ameloblastic tumors, and the level of immunoreactivity for PD-ECGF/TP was significantly higher in ameloblastomas than in tooth germs. Granular cell ameloblastomas showed PD-ECGF/TP reactivity in granular neoplastic cells as well as in stromal cells. Immunoreactivity for angiopoietin-1 and -2 was detected predominantly in odontogenic epithelial cells near the basement membrane in tooth germs and in benign and malignant ameloblastic tumors. Malignant ameloblastic tumors had decreased angiopoietin-1 reactivity and ameloblastic carcinomas had increased angiopoietin-2 reactivity as compared with the respective levels in tooth germs and ameloblastomas. Immunohistochemical reactivity for angiopoietin-2 was slightly higher in follicular ameloblastomas than in plexiform ameloblastomas. CONCLUSION: Expression of PD-ECGF/TP and angiopoietin-1 and -2 in tooth germs and ameloblastic tumors suggests that these angiogenic factors participate in tooth development and odontogenic tumor progression by regulating angiogenesis. Altered expression of PD-ECGF/TP and angiopoietins in ameloblastic tumors may be involved in oncogenesis, malignant potential, and tumor cell differentiation. 相似文献
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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. 相似文献
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BACKGROUND: To clarify the possible role of apoptotic cell death in oncogenesis and cytodifferentiation of odontogenic epithelium, apoptosis-related factors--Fas, Fas ligand (FasL), caspase-3 and single-stranded DNA (ssDNA)--were analyzed in ameloblastomas as well as in tooth germs. METHODS: Specimens of 5 tooth germs, 29 benign ameloblastomas and 5 malignant ameloblastomas were examined by immunohistochemistry using anti-Fas, FasL, caspase-3 and ssDNA polyclonal antibodies. RESULTS: Immunoreactivity for Fas and FasL was detected in normal and neoplastic odontogenic epithelial cells. Fas expression in ameloblastomas was slightly lower than that in tooth germs, whereas FasL expression was similar in tooth germs and ameloblastomas. Malignant ameloblastomas showed downregulation of Fas expression and upregulation of FasL expression, as compared with benign ameloblastomas, indicating escape from cell death attack by immune cells. Immunoreactivity for caspase-3 was detected chiefly in cells neighboring the basement membrane in tooth germs and ameloblastomas. Expression of caspase-3 and Fas tended to be low in basal cell ameloblastomas and high in desmoplastic ameloblastomas, as compared with other variants of ameloblastomas. Caspase-3 expression was more intense in malignant ameloblastomas than in tooth germs and benign ameloblastomas. Apoptotic bodies reactive with anti-ssDNA antibody were detected in normal and neoplastic odontogenic epithelial cells detached from the basement membrane. Keratinizing cells in acanthomatous ameloblastomas and granular cells in granular cell ameloblastomas showed increased numbers of apoptotic bodies and increased expression of Fas and caspase-3, as compared with other neoplastic cells. Apoptotic reactions in malignant ameloblastomas were less frequent than in benign ameloblastomas, indicating abnormal regulation of cell turnover in odontogenic epithelial cells. CONCLUSION: These apoptosis-related factors were detected in various patterns in normal and neoplastic odontogenic epithelium, suggesting that these factors might be associated with oncogenesis and cytodifferentiation of epithelial odontogenic tumors. 相似文献
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Immunohistochemical detection of uPA, uPAR, PAI-1, and maspin in ameloblastic tumors 总被引:5,自引:0,他引:5
BACKGROUND: To evaluate the roles of extracellular matrix (ECM)-degrading serine proteinase in progression of odontogenic tumors, expression of urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and maspin was analyzed in ameloblastic tumors as well as in tooth germs. METHODS: Tissue specimens of 10 tooth germs, 45 ameloblastomas, and 5 malignant ameloblastic tumors were examined immunohistochemically with the use of antibodies against uPA, uPAR, PAI-1, and maspin. RESULTS: Immunohistochemical reactivity for uPA, uPAR, PAI-1, and maspin was detected in normal and neoplastic odontogenic tissues: uPA was recognized predominantly in mesenchymal cells, uPAR was evident in epithelial cells, PAI-1 was found in both epithelial and mesenchymal cells, and maspin was expressed only in epithelial cells. The levels of uPA and uPAR immunoreactivity in ameloblastic tumors were slightly higher than the levels in tooth germs, while PAI-1 reactivity in ameloblastomas tended to be lower than that in tooth germs. The level of maspin immunoreactivity in ameloblastomas was significantly higher than that in tooth germs, and ameloblastic carcinoma showed decreased maspin reactivity. CONCLUSION: Expression of uPA, uPAR, PAI-1, and maspin in tooth germs and ameloblastic tumors suggests that interactions among these molecules contribute to ECM degradation and cell migration during tooth development and tumor progression. Altered expression of the serine proteinase and its associated molecules in ameloblastic tumors may be involved in oncogenesis of odontogenic epithelium. 相似文献
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BACKGROUND: To evaluate the roles of matrix-degrading proteinase regulators in progression of odontogenic tumors, expression of membrane-bound matrix metalloproteinase (MMP) MT1-MMP, MMP inhibitor RECK and MMP inducer EMMPRIN was analyzed in ameloblastic tumors as well as in tooth germs. METHODS: Tissue specimens of 11 tooth germs, 40 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with the use of antibodies against MT1-MMP, RECK, and EMMPRIN. RESULTS: Immunohistochemical reactivity for MT1-MMP, RECK and EMMPRIN was detected predominantly in odontogenic epithelial cells near the basement membrane in tooth germs and benign and malignant ameloblastic tumors. The level of immunoreactivity for MT1-MMP was slightly higher in benign and malignant ameloblastic tumors than in tooth germs. RECK expression was lower in ameloblastomas than in tooth germs. Follicular ameloblastomas showed significantly lower expression of RECK than plexiform ameloblastomas, and immunoreactivity for RECK in acanthomatous ameloblastomas was slightly lower than that in other cellular variants. CONCLUSION: Expression of MT1-MMP, RECK and EMMPRIN in tooth germs and ameloblastic tumors suggests that these normal and neoplastic epithelial components control MMP-dependent extracellular matrix (ECM) degradation during tooth development and tumor progression via epithelial-mesenchymal interactions. 相似文献
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Objective: 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.
Methods: Nine tooth germs, 37 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with antibodies against Bid, Bim, Bad, Noxa, and Puma.
Results: 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.
Conclusion: 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. 相似文献
Methods: Nine tooth germs, 37 ameloblastomas, and five malignant ameloblastic tumors were examined immunohistochemically with antibodies against Bid, Bim, Bad, Noxa, and Puma.
Results: 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.
Conclusion: 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. 相似文献
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Hiroyuki Kumamoto Mitsuhide Yoshida Kiyoshi Ooya 《Journal of oral pathology & medicine》2002,31(9):539-548
BACKGROUND: Tumors derived from odontogenic epithelium exhibit considerable variation and are classified into several benign and malignant entities. To clarify the role of growth factors in oncogenesis, cytodifferentiation and progression of epithelial odontogenic tumors, expression of hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-beta) and their receptors were analyzed in these tumors as well as in tooth germs. METHODS: Specimens of five tooth germs, 34 ameloblastomas, three calcifying epithelial odontogenic tumors (CEOTs), two clear cell odontogenic tumors (CCOTs), five adenomatoid odontogenic tumors (AOTs), six calcifying odontogenic cysts (COCs) and six malignant ameloblastomas were examined immunohistochemically with the use of antibodies against HGF, TGF-beta and their receptors. RESULTS: In tooth germs and epithelial odontogenic tumors, immunoreactivity for HGF and TGF-beta was detected in both epithelial and mesenchymal cells, while expression of their receptors was found only in epithelial cells. In tooth germs and main types of ameloblastomas, HGF and TGF-beta reactivity was marked in epithelial cells near the basement membrane, and their receptors were diffusely positive in most epithelial cells. In subtypes of ameloblastomas, reduced expression of HGF, c-Met and TGF-beta and increased reactivity for TGF-beta receptors were detected in keratinizing cells in acanthomatous ameloblastomas, and granular cells in granular cell ameloblastomas demonstrated little or no expression of HGF, TGF-beta or their receptors. As compared with main types of ameloblastomas, basal cell ameloblastomas showed high HGF reactivity, and desmoplastic ameloblastomas exhibited elevated reactivity for TGF-beta and its receptors. Neoplastic cells in CEOTs, AOTs and COCs showed reactivity for HGF, TGF-beta and their receptors. Elevated HGF and TGF-beta reactivity was found in pseudoglandular cells in AOTs, and high expression of their receptors was noted in ghost cells in COCs. Metastasizing ameloblastomas showed similar expression patterns of HGF, TGF-beta and their receptors to those of benign ameloblastomas, while CCOTs and ameloblastic carcinomas had increased HGF expression and low reactivity for TGF-beta and its receptors as compared with benign ameloblastomas. CONCLUSIONS: Immunohistochemical localization of HGF, TGF-beta and their receptors in tooth germs and epithelial odontogenic tumors supports the hypothesis that HGF and TGF-beta act on epithelial cells via paracrine and autocrine mechanisms. Altered expression of the agents in these epithelial odontogenic tumors, especially subtypes of ameloblastomas, AOTs and COCs, suggests that HGF and TGF-beta signaling might affect differentiation of neoplastic odontogenic epithelial cells. Activated HGF/c-Met pathway and reduced TGF-beta signaling in CCOTs and ameloblastic carcinomas may be associated with the malignant potential of these epithelial odontogenic tumors. 相似文献
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Hiroyuki Kumamoto Nobuhiro Takahashi Kiyoshi Ooya 《Journal of oral pathology & medicine》2004,33(6):360-367
BACKGROUND: To clarify the roles of rat sarcoma (Ras)/mitogen-activated protein kinase (MAPK) signaling pathway in oncogenesis and cytodifferentiation of odontogenic tumors, K-Ras gene status and expression of Ras, Raf1, MAPK/extracellular signal-regulated kinase (ERK) kinase (MEK)1, and ERK1/2 proteins were analyzed in ameloblastomas as well as in tooth germs. METHODS: Paraffin sections of 10 tooth germs and 46 benign and 6 malignant ameloblastomas were examined immunohistochemically for the expression of K-Ras, Raf1, MEK1, and ERK1/2. Frozen tissue samples of 22 benign ameloblastomas and 1 malignant (metastasizing) ameloblastoma were analyzed by direct DNA sequencing to detect K-Ras gene alteration. RESULTS: Immunohistochemical reactivity for K-Ras, Raf1, MEK1, and ERK1/2 was detected in both normal and neoplastic odontogenic epithelium, and these molecules were reactive chiefly with odontogenic epithelial cells neighboring the basement membrane. Plexiform ameloblastomas showed slightly stronger expression of these Ras/MAPK signaling molecules than follicular ameloblastomas. Keratinizing cells and granular cells showed decreased reactivity for the signaling molecules. Basal cell ameloblastomas showed slightly stronger reactivity for the signaling molecules than did the other subtypes. K-Ras immunoreactivity in malignant ameloblastomas was lower than that in dental lamina of tooth germs. Direct DNA sequencing showed a GGT to GCT point mutation at codon 12 of K-Ras gene in one ameloblastoma. Conclusion: Expression of K-Ras, Raf1, MEK1, and ERK1/2 in tooth germs and ameloblastomas suggests that Ras/MAPK signaling pathway functions to regulate cell proliferation and differentiation in both normal and neoplastic odontogenic epithelium. K-Ras gene status implied that K-Ras mutations might play a minor role in oncogenesis of odontogenic epithelium. 相似文献
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Hiroyuki Kumamoto Takahiro Suzuki Kiyoshi Ooya 《Journal of oral pathology & medicine》2002,31(10):605-611
BACKGROUND: To clarify the possible role of nitric oxide (NO) and stress proteins in oncogenesis and cytodifferentiation of odontogenic epithelium. Inducible NO synthase (iNOS) and heat shock proteins (HSPs) were analyzed in ameloblastomas as well as in tooth germs. METHODS: Specimens of seven tooth germs, 36 benign ameloblastomas and five malignant ameloblastomas were examined by immunohistochemistry using antibodies against iNOS and 27-, 60- and 70-kDa HSPs (HSP27, HSP60 and HSP70). RESULTS: Immunoreactivity for iNOS was detected in normal and neoplastic odontogenic epithelial cells and was higher in malignant ameloblastomas than in tooth germs and benign ameloblastomas. HSP27 was expressed constitutively in all odontogenic epithelial cells in tooth germs and benign and malignant ameloblastomas. Expression of HSP60 and HSP70 was detected in normal and neoplastic odontogenic epithelial cells and was prominent in cells neighboring the basement membrane. HSP60 reactivity showed no apparent difference between normal and neoplastic odontogenic epithelium, whereas HSP70 expression was slightly higher in benign and malignant ameloblastomas than in tooth germs. CONCLUSIONS: Activation of iNOS might be associated with malignant potential of epithelial odontogenic tumors. Elevated expression of HSP70 is considered to be involved in neoplastic transformation of odontogenic epithelial cells. 相似文献
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BACKGROUND: To clarify the roles of cell cycle regulation in oncogenesis and cytodifferentiation of odontogenic tumors, expression of retinoblastoma protein (RB) and E2 promoter-binding factor-1 (E2F-1) was analyzed in ameloblastomas as well as in tooth germs. METHODS: Tissue specimens of 10 tooth germs, 40 benign ameloblastomas, and five malignant ameloblastomas were examined immunohistochemically with the use of antibodies against RB, E2F-1, and phosphorylated RB. Ki-67 antigen immunostaining was made as a marker of cell proliferation. RESULTS: Immunohistochemical reactivity for RB, E2F-1, phosphorylated RB, and Ki-67 was detected in the nuclei of odontogenic epithelial cells near the basement membrane in tooth germs and benign and malignant ameloblastomas. The number of cells positive for phosphorylated RB was nearly equal to or slightly less than the number of cells positive for RB or E2F-1. The number of Ki-67-positive cells was slightly more than the numbers of cell positive for RB, E2F-1, or phosphorylated RB. The levels of immunoreactivity for RB, E2F-1, phosphorylated RB, and Ki-67 were slightly higher in benign and malignant ameloblastomas than in tooth germs. Plexiform ameloblastomas showed significantly higher expression of RB than follicular ameloblastomas. Ki-67 immunoreactivity was significantly higher in ameloblastic carcinomas than in metastasizing ameloblastomas. CONCLUSION: Similar immunoreactivity for RB, E2F-1, phosphorylated RB, and Ki-67 in tooth germs and ameloblastomas indicated cellular expression of phosphorylated RB and active-free E2F-1 in both normal and neoplastic odontogenic tissues. Expression of RB, E2F-1, and phosphorylated RB was considered to be involved in cell proliferation and differentiation of odontogenic epithelium via control of the cell cycle. 相似文献
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BACKGROUND: Expression of vascular endothelial growth factor (VEGF), a major angiogenic factor, and microvessel density (MVD), assessed by the use of anti-CD34 antibody, were immunohistochemically examined in benign and malignant ameloblastomas, as well as tooth germs, to clarify the possible role of angiogenesis in epithelial odontogenic tumors. METHODS: Specimens of 5 tooth germs, 35 benign ameloblastomas and 5 malignant ameloblastomas were examined by immunohistochemistry using anti-VEGF and CD34 monoclonal antibodies. RESULTS: Immunoreactivity for VEGF was detected in both normal and neoplastic odontogenic epithelial cells, and weakly in microvessels near odontogenic epithelial cells, suggesting that this angiogenic factor acts on endothelial cells via a paracrine mechanism in odontogenic tissues. Both benign and malignant ameloblastomas showed elevated VEGF expression as compared to tooth germs. VEGF expression was low in keratinizing cells in acanthomatous ameloblastomas and granular cells in granular cell ameloblastomas, and acanthomatous ameloblastomas showed the lowest VEGF reactivity among the subtypes of ameloblastomas. MVD in both benign and malignant ameloblastomas was higher than that in tooth germs, indicating increased demands for blood in the neoplastic tissues. CD34-positive microvessels in follicular ameloblastomas were numerous and small, whereas those in plexiform ameloblastomas were scattered and dilated. MVD tended to depend on VEGF expression levels in both benign and malignant ameloblastomas. CONCLUSIONS: VEGF was considered to be an important mediator of angiogenesis in these epithelial odontogenic tumors, and up-regulation of VEGF might be associated with neoplastic or malignant changes of odontogenic epithelial cells. 相似文献
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BACKGROUND: To clarify the roles of the Wnt signaling pathway in oncogenesis and cytodifferentiation of odontogenic tumors, expression of beta-catenin and adenomatous polyposis coli (APC) was analyzed in ameloblastomas as well as in tooth germs. METHODS: Tissue specimens of 10 tooth germs, 40 benign ameloblastomas, and five malignant ameloblastomas were examined immunohistochemically with the use of antibodies against beta-catenin and APC. RESULTS: Immunohistochemical reactivity for beta-catenin was detected in the cell membrane and cytoplasm of most odontogenic epithelial cells in tooth germs and ameloblastomas. Nuclear beta-catenin expression was recognized in nine of 40 ameloblastomas and two of five malignant ameloblastomas, but not in tooth germs. APC was evidently expressed in odontogenic epithelial cells neighboring the basement membrane in tooth germs and ameloblastomas, and the reactivity was significantly lower in benign and malignant ameloblastomas than in tooth germs. Follicular ameloblastomas and acanthomatous ameloblastomas tended to show high nuclear beta-catenin expression and low APC reactivity, as compared with other ameloblastoma variants. CONCLUSION: Expression of beta-catenin and APC in tooth germs and ameloblastomas suggests that aberration of the Wnt signaling pathway might play a role in oncogenesis and cytodifferentiation of odontogenic epithelium via deregulation of cell proliferation. 相似文献
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Hiroyuki Kumamoto Takashi Izutsu Kousuke Ohki Nobuhiro Takahashi Kiyoshi Ooya 《Journal of oral pathology & medicine》2004,33(5):292-299
BACKGROUND: To clarify the roles of the p53-MDM2-p14(ARF) cell cycle regulation system in oncogenesis and cytodifferentiation of odontogenic tumors, p53 gene status and expression of p53, MDM2, and p14(ARF) proteins was analyzed in ameloblastomas as well as tooth germs. METHODS: Paraffin sections of 16 tooth germs and 46 benign and 5 malignant ameloblastomas were examined immunohistochemically for the expression of p53, MDM2, and p14(ARF) proteins. Frozen tissue samples of 10 benign ameloblastomas and 1 malignant (metastasizing) ameloblastoma were analyzed by direct DNA sequencing to detect p53 gene alteration. RESULTS: Immunohistochemical reactivity for p53 was detected in 2 of 13 tooth germs, 13 of 29 ameloblastomas, and 5 of 5 malignant ameloblastomas, and the expression ratio of p53 in tooth germs was significantly lower than those in benign and malignant ameloblastomas. Direct DNA sequencing showed no alteration of p53 gene exons 5-8 in any sample of 10 benign ameloblastomas and 1 metastasizing ameloblastoma. Expression of MDM2 and p14(ARF) was detected in all samples of normal and neoplastic odontogenic epithelium, and the expression ratios in tooth germs tended to be lower than those in benign and malignant ameloblastomas. In ameloblastomas, expression of p53, MDM2, and p14(ARF) was significantly higher in plexiform cases than in follicular cases. Markedly decreased reactivity for p53, MDM2, and p14(ARF) was detected in keratinizing and granular cells in ameloblastoma subtypes. Basal cell ameloblastoma showed slightly higher reactivity for p53, MDM2, and p14(ARF) as compared with other subtypes. CONCLUSION: Elevated expression of p53, MDM2, and p14(ARF) in benign and malignant ameloblastomas suggests that alteration of the p53-MDM2-p14(ARF) cascade is involved in oncogenesis and/of malignant transformation of odontogenic epithelium. p53 gene status implied that p53 mutation might play a minor role in neoplastic changes of odontogenic epithelium. Immunoreactivity for p53, MDM2, and p14(ARF) in ameloblastoma variants suggests that these factors might be associated with tissue structuring and cytodifferentiation of ameloblastomas. 相似文献
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OBJECTIVE: To further clarify the roles of regulators of embryonic development, bone morphogenetic protein (BMPs) and their associated molecules, in oncogenesis and cytodifferentiation of odontogenic tumors, the expression of these regulator molecules were analyzed in epithelial odontogenic tumors as well as in tooth germs. MATERIALS AND METHODS: Tooth germs, ameloblastomas, adenomatoid odontogenic tumors, and malignant ameloblastomas were examined by RT-PCR and immunohistochemistry for detection of BMP-2, -4, -7, BMP receptors I and II (BMPR-I, BMPR-II), core-binding factor alpha1 (CBFA1), and osterix. RESULTS: mRNA expression of BMPs, BMPRs, CBFA1, and osterix was detected in all odontogenic tissues. Immunohistochemical reactivity for BMPs, BMPRs, and CBFA1 was detected in both epithelial and mesenchymal cells of tooth germs and epithelial odontogenic tumors. BMPs and BMPRs were evidently expressed in odontogenic epithelial cells in tooth germs and epithelial odontogenic tumors. Acanthomatous ameloblastomas showed increased BMP-7 reactivity in keratinizing cells. Nuclear CBFA1 expression was detected scatteredly in odontogenic epithelial cells in normal and neoplastic odontogenic tissues, as well as in some mesenchymal cells in tooth germs and in some stromal cells in epithelial odontogenic tumors. Ameloblastic carcinomas showed low reactivity for BMPs, BMPRs, and CBFA1. CONCLUSION: BMPs and their associated molecules might play a role in cytodifferentiation of normal and neoplastic odontogenic epithelium via epithelial-mesenchymal interactions. 相似文献
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Detection of Notch signaling molecules in ameloblastomas 总被引:1,自引:0,他引:1