Immunohistochemical demonstration of enamel proteins in odontogenic tumors

Immunohistochemical localization of two enamel proteins, amelogenin and enamelin, in comparison with that of keratin, was determined in odontogenic tumors and the allied lesions in order to verify functional differentiation of the tumor cells as ameloblasts. Amelogenin and enamelin were demonstrated in small mineralized foci and in the tumor cells surrounding them in adenomatoid odontogenic tumor (AOT), calcifying epithelial odontogenic tumor (CEOT), and calcifying odontogenic cyst (COC). Hyaline droplets in AOT showed positive staining for both enamel proteins. These mineralized and hyaline materials were not positive for keratin, although tumor cells were positive. On the other hand, no immunoreaction for enamel proteins was obtained in ameloblastoima and odontogenic epithelial cell nests within myxoma and epulis. The results suggest that tumor cells of AOT and CEOT and lining epithelial cells of COC show ameloblastic differentiation in part, but that ameloblastoma cells do not attain functional matauration as secretory phase ameloblasts.     

Expression of odontogenic ameloblast-associated protein, amelotin, ameloblastin, and amelogenin in odontogenic tumors: immunohistochemical analysis and pathogenetic considerations

Screening for expression of amelogenesis-related proteins represents a powerful molecular approach to characterize odontogenic tumors and investigate their pathogenesis. In this study, we have examined the presence and distribution of odontogenic ameloblast-associated protein (ODAM), amelotin (AMTN), ameloblastin (AMBN), and amelogenin (AMEL) by immunohistochemistry in samples of adenomatoid odontogenic tumor (AOT), calcifying epithelial odontogenic tumor (CEOT), developing odontoma, ameloblastoma, calcifying cystic odontogenic tumor (CCOT), ameloblastic fibroma (AF), myxoma, odontogenic fibroma (OF), and reduced enamel epithelia (REE). Positive results were obtained in those tumors with epithelial component, except for AF, OF, and ameloblastoma. ODAM was found around mineralized structures (dystrophic calcifications) and CEOT's amyloid, whereas AMTN stained the eosinophilic material of AOTs. The CCOT transitory cells to ghost cells were strongly positive with all proteins except AMEL, and the REE as well as odontomas showed immunoexpression for ODAM, AMTN, AMBN, and AMEL similar to those found in normal rat tooth germs. Based on these results, some histopathogenetic theories were formulated.     

Immunohistochemical demonstration of bone morphogenetic protein in odontogenic tumors

The aim of the present study was to describe the expression and distribution of bone morphogenetic protein (BMP) in odontogenic tumors by immunohistochemistry using monoclonal antibody against bovine BMP (BMPMcAb). Eight types of odontogenic tumors (44 cases), including ameloblastoma (20 cases), cementifying fibroma (8 cases), benign cementoblastoma (5 cases), dentinoma (3 cases), compound odontoma (2 cases), adenomatoid odontogenic tumor (2 cases), calcifying epithelial odontogenic tumor (2 cases) and odontogenic fibroma (2 cases), were studied. The results showed that, according to the immunostaining pattern of BMPMcAb, tumors could be classified into two types: all cementifying fibro-mas, benign cementoblastomas. Dentinomas, odontogenic fibromas. and compound odontomas demonstrated a positive reaction, whereas all ameloblastomas, adenomatoid odontogenic tumors, and calcifying epithelial odontogenic tumors were negative. BMPMcAb-positive odontogenic tumors were those tumors with formation of enamel, dentin, cementum or bone. Therefore. BMP might play an important role in the formation of calcified dental tissues and the development of odontogenic tumors contaning such tissues.     

骨外型牙源性钙化上皮瘤

骨外型牙源性钙化上皮瘤极为罕见,通过复习1966～2011年英文MEDLINE与1994～2011年中文CHKD中收录的文献,仅有37例骨外型牙源性钙化上皮瘤的个案报告。根据上述资料分析,发现该瘤具有以下临床特点,就诊年龄3～71岁,平均35.8岁;男13例,女19例,男女比例为1∶1.46;肿块直径0.5～4 cm,平均1.76 cm;好发部位主要是牙龈,累及下颌与上颌牙龈的比例为1∶1;组织学特征表现与骨内型牙源性钙化上皮瘤基本相同;复发率为5.4%。因该瘤具有浅表骨侵蚀能力,应行完整的肿瘤切除结合骨面刮治术。     

Glandular odontogenic cyst: analysis of cytokeratin expression and clinicopathological features

The glandular odontogenic cyst (GOC) is a rare odontogenic cyst which is still controversial in regard to classification, terminology, and origin. The first Japanese case of GOC is reported. Immunohistochemical examination for expression of cytokeratins and epithelial membrane antigen by monoclonal antibodies suggested that the lining epithelium was of odontogenic origin with metaplastic mucus-laden cells. We have reviewed the literature and compared the clinicopathological findings of the reported case of GOC with those of botryoid odontogenic cysts (BOC). The anatomical location, age range, and sex of GOC cases were very similar to those of BOC. GOC appears to be a multilocular and mucoe-pidermoid variant of non-keratinizing odontogenic cysts, which also includes BOC. GOC should be separated from the other types of odontogenic cyst and central mucoepidermoid tumours of salivary gland origin.     

Glandular odontogenic cyst in China: report of 12 cases and immunohistochemical study

OBJECTIVE: The purpose of this study was to present 12 additional cases of glandular odontogenic cyst (GOC) in the Department of Oral Pathology, School of Stomatology, Wuhan University, People's Republic of China, and to investigate their immunohistochemical cytokeratins (CKs) expression in the epithelial components. METHODS: A total of 12 GOCs were reviewed clinically and radiographically, and immunohistologic CKs AE1, 7, 8/18, 10/13, 14, 16, 19 and 20 were performed by using a standard biotin-streptavidin immunoperoxidase technique on paraffin sections. RESULTS: The present series showed that eight occurred in males and four in females. The mean age was 37.6 years with a peak incidence occurring in the third decades (six of 12). Mandibles were more affected than maxillas (7:5), especially anterior mandible (four of seven). Radiographically, ratio multilocular to unilocular radiolucencies was 5:7 usually with well-defined borders. Histologically, cystic spaces were lined by non-keratinized stratified epithelia containing focal plaque-like or whirlpool-like thickenings; surface epithelial layer-containing eosinophilic cuboidal cells; mucous cells; and mucin pools of microcystic areas in the epithelium. Immunohistochemistry showed that epithelium of GOCs stained for CKs AE1, 7, 8/18, 10/13, 14 and 19 with slight changes in their patterns, and no reaction to CKs 16 and 20. CONCLUSIONS: Most clinical and histologic features in this study were analogous to those reported west population, although with slight difference between them. Histologically, the morphology of the epithelium strongly suggested an odontogenic origin, and CKs expression of GOC was similar to that of odontogenic epithelium, suggesting histochemically that GOC might be derived from odontogenic epithelium.     

Immunohistochemical detection of hepatocyte growth factor, transforming growth factor-β and their receptors in epithelial odontogenic tumors

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.     

Molecular pathology of odontogenic tumors

Odontogenic tumors are lesions derived from the elements of the tooth-forming apparatus and are found exclusively within the jawbones. This review represents a contemporary outline of our current understanding of the molecular and genetic alterations associated with the development and progression of odontogenic tumors, including oncogenes, tumor-suppressor genes, oncoviruses, growth factors, telomerase, cell cycle regulators, apoptosis-related factors, regulators of tooth development, hard tissue-related proteins, cell adhesion molecules, matrix-degrading proteinases, angiogenic factors, and osteolytic cytokines. It is hoped that better understanding of related molecular mechanisms will help to predict the course of odontogenic tumors and lead to the development of new therapeutic concepts for their management.     

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牙源性肿瘤是颌骨最常见病损之一,临床上绝大多数牙源性肿瘤均发生在颌骨内。良性肿瘤多无自觉症状,直至肿瘤生长到一定程度出现颌面部组织膨隆方被发现,早期患者多是在做牙髓治疗或体检照片时无意中发现的,除非继发感染,患者一般没有疼痛等不适感觉。牙源性肿瘤的病理学分类很多,基于局部生物学行为的特点,WHO在2005年将原来的牙源性角化囊肿和牙源性钙化囊肿归列入牙源性肿瘤。牙源性肿瘤的临床表现多样,一般需要结合病理学检查确诊。手术处理是治疗牙源性肿瘤惟一有效的方法,但如何选择有效术式是临床医师需要慎重考虑的问题。本文就几种常见牙源性肿瘤的外科治疗作了简要概述。     

骨外型牙源性钙化上皮瘤1例报告

牙源性钙化上皮瘤是一种良性肿瘤，也称Pindborg瘤，可分为骨内型和骨外型2种，主要发生于颌骨内，偶见于颌骨外。本文报告1例发生于口底的牙源性钙化上皮瘤，其临床症状与口底皮样囊肿相似．术后经组织病理学确诊，主要组织病理学特征是嗜酸性环状钙化团块。因其具有局部侵袭性，为避免复发，提倡完整切除肿物。     

Significance of podoplanin expression in keratocystic odontogenic tumor

J Oral Pathol Med (2010) 39 : 110–114
Background:  The most important clinical features of the keratocystic odontogenic tumor (KCOT) are its potential for locally destructive behavior, a tendency to recur, and its origin in the odontogenic epithelium. The clinical features of KCOT are similar to those of ameloblastoma (AM). Histologically, KCOT is distinguished from jaw cyst with keratinization (orthokeratinized odontogenic cyst; OOC). However, current scientifically based clinical parameters cannot predict any potential for neoplastic behavior, or aggressive and localized invasiveness, in patients with KCOT. We have shown that podoplanin, a lymphatic endothelial marker, is highly expressed in AM. The purpose of this study was to determine the usefulness of podoplanin for reclassification of the odontogenic keratocyst (OKC) from cyst to tumor status.
Methods:  Paraffin-embedded tissue specimens of 57 OKCs (46 KCOTs and 11 OOCs) and 15 dentigerous cysts (DCs) were immunohistochemically examined using antibody against podoplanin.
Results:  Immunohistochemical reactivity for podoplanin was detected in the cell membrane and cytoplasm of most of the basal and suprabasal layer, areas of budding basal cell proliferation, epithelial nests and peripheral cells of daughter cysts in the stromal connective tissue in KCOTs. In the case of OOC and DC, only cases associated with inflammation were positive for podoplanin.
Conclusion:  Podoplanin is strongly expressed in KCOTs in comparison with OOCs. The pattern of staining for podoplanin in KCOT could be related to its neoplastic nature, and suggests a role of the protein in tumor invasiveness.     

Cystic variant of calcifying epithelial odontogenic tumor

The calcifying epithelial odontogenic tumor is a rare benign odontogenic neoplasm of the jaw. Clinically, calcifying epithelial odontogenic tumor manifests as an intraosseous lesion (central type) in the majority of cases (95%). Extraosseous or peripheral lesions account for less than 5% of cases. Calcifying epithelial odontogenic tumor can be associated with an impacted tooth and give a radiographic simulation of dentigerous cyst. Most calcifying epithelial odontogenic tumors are solid in nature, histopathologically, and might have few cyst-like spaces within them. However, a true cystic calcifying epithelial odontogenic tumor is a rare possibility. We describe a case of a true cystic variant of calcifying epithelial odontogenic tumor in a 30-year-old male, which to our knowledge, is only the second reported case.     

Epidermal growth factor receptor in odontogenic cysts and tumors

The expression of epidermal growth factor receptor (EGFR) was investigated in 67 cases of odontogenic cysts and 35 cases of odontogenic tumors using monoclonal antibody to EGFR (Biomarker, Israel) to determine the presence and significance of this transmembrane growth factor receptor. The cystic epithelial cells of odontogenic cystic lesions (keratocyst 60%; primordial cyst 75%; radicular cyst 35%; and follicular cyst 47.4%) were positive to EGFR staining. Cytochemical characterization of EGFR in those cystic epithelium was cell membrane positive type as in the normal epithelium. No expression of EGFR was found in the odontogenic tumors. This diversity of EGFR represents no binding activity of EGF, or loss of EGFR in the tumor cell upon EGFR mediated growth in odontogenic tumors was suggested a different tumor cell growth factor status or microenvironment in cell proliferation mechanism at the cellular level in cysts and tumors of odontogenic origin.     

Malignant transformation of calcifying epithelial odontogenic tumour with solitary pulmonary metastasis

This report describes the management of a case of calcifying epithelial odontogenic tumour (CEOT) that underwent malignant transformation and metastasized to the lung. The solitary pulmonary metastasis was discovered incidentally on computed tomography (CT) imaging of the neck. It appears that only one previous case with proven pulmonary metastasis has been reported in the literature, which involved multiple pulmonary deposits managed with platinum chemotherapy. The long-term prognosis of metastatic CEOT is therefore unknown. In the case presented here, the patient was managed successfully with surgery alone. There is often diagnostic uncertainty because histological features of benign, recurrent, and malignant CEOT are not dissimilar. Ki-67 immunohistochemistry is helpful, as higher levels are more indicative of malignancy. We consider that in cases of suspected recurrent and malignant CEOT, CT imaging of the thorax and abdomen as part of follow-up may identify metastases early, resulting in earlier treatment, an improved prognosis, and reduced morbidity and mortality.     

Ameloblastoma, calcifying epithelial odontogenic tumor, and glandular odontogenic cyst show a distinctive immunophenotype with some myoepithelial antigen expression

Background:  Odontogenic neoplasms have some morphologic overlap with salivary gland neoplasms, many of which show myoepithelial differentiation. In the 1980s, an ultrastructural study identified a population of myoepithelial-like cells in calcifying epithelial odontogenic tumor. Myoepithelial derived tumors have since been shown to have distinct immunohistochemical profiles.
Methods:  We examined a series of odontogenic neoplasms, including 11 ameloblastomas, four calcifying epithelial odontogenic tumors, five glandular odontogenic cysts (GOCs), and five keratocystic odontogenic tumors with a panel of myoepithelial-associated immunohistochemical stains. We also assessed representative control examples of oral mucosa, odontogenic rests, and dentigerous cysts.
Results:  All of the neoplastic and non-neoplastic oral epithelium-derived entities share a p63-positive, high molecular weight cytokeratin (CK5/6)-positive immunophenotype. Calponin reactivity was at least focally present in two of four calcifying epithelial odontogenic tumors, three of five GOCs, and 10 of 11 ameloblastomas; the sole completely non-reactive ameloblastoma represents a lung metastasis. One case of calcifying epithelial odontogenic tumor was focally positive for glial fibrillary acidic protein. However, other more definitive markers of myoepithelial differentiation, including S-100 and smooth muscle actin, were negative. Two of three calcifying epithelial odontogenic tumors and five of five GOCs were also positive for a low molecular weight cytokeratin (CK7).
Conclusions:  Ameloblastomas, GOCs, and calcifying epithelial odontogenic tumors show a distinctive immunophenotype which overlaps with that of myoepithelial-derived salivary gland neoplasms but does not provide definitive support for myoepithelial differentiation.     

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由于颌骨内的成牙组织常可作为囊肿和肿瘤的组织来源,因此颌骨是人类骨骼中最好发上皮性囊肿和肿瘤的部位。这类牙源性病损好发于年轻人,可造成颌骨及邻近组织的破坏,导致口腔颌面部外形改变,某些侵袭性病损具有较高的复发倾向,可对患者的生存质量及心理健康造成严重影响。本文着重讨论几种常见的牙源性囊肿与牙源性肿瘤的病理学诊断。