Co-expression of Ki-67 and p53 protein in ameloblastoma and keratocystic odontogenic tumor

Abstract Objectives. The purpose of this study was to evaluate the cell proliferation and p53 protein expression in ameloblastomas (ABs), keratocystic odontogenic tumor (KCOT) and dentigerous cyst (DC). Method. The immunohistochemistry were carried out for Ki-67 and p53 protein expression by using MIB-1 clone and DO-7 clone, respectively, in ABs (n = 23), KCOT (n = 32), DC (n = 30), normal oral mucosa (NOM) (n = 12) and fetal oral mucosa (FOM) (n = 10). Results. Both the Ki-67 LI Labeling index (LI) and p53 LI was significantly higher in ABs than KCOT, DC, NOM and FOM. The Ki-67 LI and p53 LI was significantly higher in KCOT as compared to DC. Ki-67 LI and p53 LI was observed in descending order in ABs, KOCT, FOM, NOM and DC. There was significant correlation between Ki-67 expression and p53 expression in ABs, KCOT, DC and NOM. The densely stained p53 positive cells were noted higher in ABs than KCOT. The very few densely p53 positive cells were noted in DC, NOM and FOM. Conclusion. The results suggest that the p53 protein expression does not necessarily imply an association with malignant disease and/or p53 gene mutation, but a tendency to be expressed in an increasing quantitative and qualitative manner, as the biologic behavior of odontogenic cyst or tumors becomes more aggressive. p53 over-expression may promote cell proliferation in odontogenic lesions. Thus, it can be stipulated that Ki-67 and p53 protein expression can be used as a prognostic marker in odontogenic lesions.     

同源盒基因HOXC13在牙源性肿瘤中的表达

目的:检测同源盒基因HOXC13 mRNA在牙源性肿瘤中的表达,探讨其发生的意义。方法:采用原位杂交法检测47例成釉细胞瘤(ameloblastoma,AB)(原发29例,复发14例,恶变4例)、3例牙源性钙化囊性瘤(CCOT)、3例成釉细胞纤维瘤(AF)、2例牙源性钙化上皮瘤(CEOT)、10例牙源性角化囊性瘤(KCOT)的HOXC13 mRNA水平,同时选取7例正常口腔黏膜上皮作为对照。采用SPSS10.0软件包对数据进行χ2检验。结果:HOXC13 mRNA在AB中的阳性率为97.9%(46/47),CCOT中为100%(3/3),CEOT中为100%(2/2),KCOT上皮中为70.0%(7/10),正常口腔黏膜细胞中为42.9%(3/7),AB、KCOT、正常黏膜3组间差异显著(Ρ=0.001),但角化及颗粒样变退化细胞却为阴性。3例AF均为阴性。结论:牙源性肿瘤的发生、发展与HOXC13的高表达有关,且受其调控。HOXC13 mRNA在牙源性病损上皮中表达有异质性,该基因可促进上皮增殖,阻抑成釉细胞的终末分化,其丢失可导致上皮细胞角化和退变。     

Peripheral odontogenic tumours--differential diagnosis in gingival lesions

Peripheral odontogenic tumours (POT) are rare benign focal overgrowths of the oral soft tissue, usually occurring in the gingiva. Between 1996-2000, 6 out of 406 excised gingival lesions were diagnosed as POT (1.5%). Tumours included peripheral odontogenic fibroma (2 patients), peripheral calcifying odontogenic cyst (2 patients), peripheral ameloblastoma (1 patient), and peripheral calcifying epithelial odontogenic tumour (1 patient). Review of the literature reveals that peripheral odontogenic fibroma and peripheral ameloblastoma were the most common POT. The purpose of this article was to analyse the clinical data of these tumours according to the presented cases and the literature review, to elucidate typical features of each tumour type and enhance easy identification.     

Analysis of the neoplastic nature and biological potential of sporadic and nevoid basal cell carcinoma syndrome-associated keratocystic odontogenic tumor

BACKGROUND: Keratocystic odontogenic tumor (KCOT), also known as odontogenic keratocyst, is a benign cystic neoplasm, which may be associated with nevoid basal cell carcinoma syndrome (NBCCS) and if it does, will occur as multiple cystic lesions. KCOT is locally destructive despite its bland histological features. However, the neoplastic nature of KCOT is not well established. Heparanase is an endo-d-glucuronidase enzyme that specifically cleaves heparan sulfate (HS) and the increase of its level in tumors promotes invasion, angiogenesis, and metastasis. METHODS: To investigate the neoplastic character of KCOT, we studied the localization patterns of heparanase in KCOT, focusing on the differences between sporadic and NBCCS-associated KCOTs, by immunohistochemistry and in situ hybridization. To compare the expression pattern of these cysts with non-tumorous odontogenic developmental cyst, dentigerous cyst was included. RESULTS: All the odontogenic cysts showed positive immunoreaction for heparanase protein in various intensities. The expression pattern of heparanase gene corresponded to that of protein expression. Interestingly, intense gene and protein expressions were observed in KCOT associated with NBCCS compared with sporadic ones and dentigerous cyst. CONCLUSIONS: The results implied that heparanase expression may be correlated with the neoplastic properties of KCOT, particularly in NBCCS-associated cases.     

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.     

Keratocystic odontogenic tumor: case report with CT and ultrasonography findings

Keratocystic odontogenic tumor (KCOT) is a benign odontogenic tumor with a potentially aggressive and infiltrative behavior. KCOT is most commonly occurred in mandible and demonstrate a unilocular, round, oval, scalloped radiolucent area, while large lesions may appear multilocular. An important characteristic of KCOT is its propensity to grow in an antero-posterior direction within medullary cavity of bone causing minimal expansion. Definitive diagnosis relies on histological examination. In this report, a KCOT that had an expansion both buccal and lingual cortical bone is described including its features in computed tomography and ultrasonographic exams. The lesion was removed surgically via an intraoral approach under local anesthesia and histologically reported as a KCOT.     

Prevalence of developmental odontogenic cysts in children and adolescents with emphasis on dentigerous cyst and odontogenic keratocyst (keratocystic odontogenic tumor)

Objective. To investigate the incidence and prevalence of developmental odontogenic cysts in children and adolescents and compare the features of the two most common types, dentigerous cyst and keratocystic odontogenic tumor (KCOT). Study design. A retrospective review in a series of 369 patients with all histological diagnoses of developmental odontogenic cysts in children (≤12 years) and adolescents (13–18 years) was conducted. Results. Among these, 361 (97.8%) patients were diagnosed as dentigerous cyst (n = 281) and KCOT (n = 80), with the male-to-female ratios of dentigerous cyst and KCOT both being 2:1. The average age of the patients with KCOT was older than that of those with dentigerous cyst (14.7 years vs 11.8 years, p < 0.001). Dentigerous cyst (59.1%) was more common in children, but KCOT (78.8%) was more common in adolescents (p < 0.001). Dentigerous cyst (57.6%) predominantly located on the maxilla, but KCOT (60.3%) predominantly located on the mandible (p = 0.010). Conclusions. Adolescent patients with lesions located on the mandible would favor KCOT over dentigerous cyst. This study aids in better knowledge of the prevalence of developmental odontogenic cysts in a large pediatric population, and shows that a well-supported early diagnosis is indispensable for a more adequate treatment.     

Recurrent keratocystic odontogenic tumor in the masseter muscle overlying the boney perforations: a case report

Keratocystic odontogenic tumor (KCOT) is a benign intraosseous neoplasm of odontogenic origin with high recurrence rates and tendency to invade adjacent tissue. Most recurrences occur in the first 5 years after surgery and are usually located at the site of the primary tumor in the jaws. We report a rare case of KCOT which recurred in the masseter muscle 14 years after segmental mandibulectomy and autogenous frozen lesional mandible reimplantation. The patient had undergone enucleation of KCOT in the right mandible 20 years before segmental mandibulectomy. This case could further demonstrate the aggressive behavior of KCOT.     

Simultaneous palatal pleomorphic adenoma and mandibular keratocystic odontogenic tumor in a pediatric patient

BACKGROUND: Neoplasms of the salivary gland account for 3% of all head and neck tumors; most of these occur in the parotid gland and are benign; 80% of them are pleomorphic adenomas. Benign neoplasms of the salivary gland are rare in children compared with adults. Keratocystic odontogenic tumor (KCOT) is considered the second most frequent neoplasm of all odontogenic tumors after the ameloblastoma. In the present report, we introduce the unusual presentation of a child with a simultaneous pleomorphic adenoma of the right hard palate and a KCOT of the left mandibular angle. DISCUSSION: The case is significant for 2 reasons; according to the literature, there are few reports of pleomorphic adenoma arising from a minor salivary gland of the palate in a patient younger than 18 years. This is to our knowledge the first recorded instance of simultaneous palatal pleomorphic adenoma and mandibular KCOT occurring in a child.     

Surgical management of dentigerous cyst and keratocystic odontogenic tumor in children: a conservative approach and 7-year follow-up

Dentigerous cyst (DC) is one of the most common odontogenic cysts of the jaws and rarely recurs. On the other hand, keratocystic odontogenic tumor (KCOT), formerly known as odontogenic keratocyst (OKC), is considered a benign unicystic or multicystic intraosseous neoplasm and one of the most aggressive odontogenic lesions presenting relatively high recurrence rate and a tendency to invade adjacent tissue. Two cases of these odontogenic lesions occurring in children are presented. They were very similar in clinical and radiographic characteristics, and both were treated by marsupialization. The treatment was chosen in order to preserve the associated permanent teeth with complementary orthodontic treatment to direct eruption of the associated permanent teeth. At 7-years of follow-up, none of the cases showed recurrence.     

Odontogenic tumours: 240 cases diagnosed over 31 years at a Brazilian university and a review of international literature

This study describes the epidemiology and clinical presentation of odontogenic tumours (OT) seen at a regional Brazilian oral and maxillofacial pathology service; to assess the quantitative impact of the most recent World Health Organization (WHO) classification of these lesions; and to compare this series with others available in international databases. The study was carried out by retrospectively analysing 240 cases diagnosed from 1978 to 2009, followed by a comprehensive review of the literature. The patients’ mean age was 29 years, with a male to female ratio of 1:1.1. Benign lesions comprised 97.9% of the cases (mostly keratocystic odontogenic tumours (KCOT), odontomas and ameloblastomas) with the remaining tumours depicting a prevalence of less than 5%. Adenomatoid OT were less frequent than in most previous studies, while malignant OT were strikingly numerous. Most OT in children and in the anterior maxilla were odontomas, while maxillary ameloblastomas were rare. Lack of swelling was more frequent in KCOT than in ameloblastomas. The present study confirms the relative impact of KCOT in the epidemiology of OT and identifies more similarities between the present series with reports from the United States and Europe than with African and Asian populations.     

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提要：外周性牙源性肿瘤又称骨外型牙源性肿瘤或软组织牙源性肿瘤,主要发生在牙龈,包括牙源性真性肿瘤及错构瘤。外周性牙源性肿瘤约占所有牙源性肿瘤的4%左右,英文文献表明其中外周性牙源性纤维瘤最多见,其次是外周性成釉细胞瘤及外周性牙源性钙化囊性瘤。外周性牙源性肿瘤临床上容易与牙龈发生的炎症性或反应性病变相混淆,明确诊断依赖组织病理学检查。外周性牙源性肿瘤不包括骨内型牙源性肿瘤穿破骨皮质侵犯牙龈。外周性牙源性肿瘤预后普遍好于相应的骨内型肿瘤,但切除不彻底仍可复发,建议长期随访。     

Peripheral odontogenic tumor: a clinicopathologic study of 30 cases. General features and hamartomatous lesions

BACKGROUND: Peripheral odontogenic tumors (POT), either neoplastic or hamartomatous, are rare. This study briefly summarizes the general features of POT and selectively reviews the histomorphologic spectrum of under-recognized hamartomatous lesions that we have designated peripheral odontogenic hamartomas (POH) in order to shed more light into the pathogenesis of POT. METHODS: Archival material accessioned at our institutions between 1970 and 2004 was systematically searched to identify examples of POT/POH. RESULTS: Among 39 660 biopsies, we retrieved 25 cases of 'classical' POT and five cases of 'unique' POH. Odontogenic fibroma and ameloblastoma were by far the most common. Of POH, two purely epithelial lesions showed multiple strands of basaloid rests [odontogenic gingival epithelial hamartoma (OGEH)] and a conglomerate of polyhedral epithelium, ghost cells and concentric calcifications (calcifying epithelial odontogenic tumor-like hamartoma), respectively. OGEH and peripheral squamous odontogenic tumor (PSOT) deserve to be a related entity. In two types of mixed POH, ectomesenchymal elements appeared juxtaposed to the squamous lining (gingival cyst-like organoid hamartoma) and ghost cells aggregated in the enamel organ of a microdont (peripheral odontoma). None of POH exhibited continuity with the surface epithelium. CONCLUSION: On the basis of this relatively limited series of cases, POH, to conceptualize a unified histogenetic source, are speculated to arise from the soft-tissue remnants of dental lamina. Gingival rests of Serres seem to retain the ability to pursue epithelial-ectomesenchymal interactions that are necessary leading to odontoma formation.     

Three-dimens?onal cone-beam computed tomography for diagnos?s of keratocystic odontogenic tumours; Evaluation of four cases

The keratocystic odontogenic tumour (KCOT), formerly known as the odontogenic keratocyst (OKC) is a benign intraosseous lesion that derives from remnants of the dental lamina. Due to its characteristics, clinical and histopathological features and various treatment approaches, this pathology is different comparing with other odontogenic cysts. Radiographically the KCOT appears as well-defined unilocular or multilocular radiolucency with thin radiopaque borders. In most cases, conventional radiographic imaging, such as panoramic views and intraoral periapical films, are adequate to determine the location and estimate the size of an KCOT. However, the clinical use for cone-beam computed tomography (CBCT) in oral and maxillofacial surgery increases and provides additional information about the contents and borders of the large lesions. In the present cases, the diagnostic performances of CBCT versus panoramic radiograph for four KCOTs were evaluated. It was concluded that appearance of lesions in the maxillofacial region could be better documented in the correct dimensions by CBCT versus panoramic radiograph. Key words:Odontogenic keratocyst, cone-beam computed tomography, three dimensional, panoramic radiograph.     

Calretinin Expression in Unicystic Ameloblastoma: An Aid in Differential Diagnosis

Calretinin is a 29 kDa calcium-binding protein, which is widely expressed in the central and peripheral neural tissue. It has also been demonstrated in odontogenic epithelium during odontogenesis and in neoplastic odontogenic tissues. The lining epithelium of eight cases of unicystic ameloblastoma, six cases of dentigerous cyst, six cases of odontogenic keratocyst, reclassified as keratocystic odontogenic tumor (KCOT), and four cases of solid/multicystic ameloblastoma was examined for the expression of calretinin. No positive staining was observed in any of the dentigerous cysts and keratocystic odontogenic tumor linings. In comparison, coarse dark brown staining was seen in the stellate reticulum of solid multicystic ameloblastoma and more superficial epithelial layers of unicystic ameloblastoma. In conclusion, we have highlighted calretinin to be a specific immunohistochemical marker for neoplastic ameloblastic tissue that can be used as an important diagnostic aid in the differential diagnosis of unicystic ameloblastoma and cystic odontogenic lesions.     

Bcl—xL、Livin在牙源性角化囊性瘤组织中的表达及意义

目的：检测Bcl-xL、Livin在牙源性角化囊性瘤囊壁上皮细胞中的表达,初步探讨凋亡抑制蛋白在牙源性角化囊性瘤发生发展中的意义。方法：免疫组化法检测32例牙源性角化囊性瘤,30例单囊型成釉细胞瘤及30例含牙囊肿手术切除标本中Bcl-xL、Livin蛋白的表达。结果：Bcl-xL在牙源性角化囊性瘤、单囊型成釉细胞瘤及含牙囊肿中的阳性表达率分别为84．38％、90．00％、36．67％,Bcl-xL在牙源性角化囊性瘤中的阳性表达率高于含牙囊肿。 Livin在牙源性角化囊性瘤、单囊型成釉细胞瘤及含牙囊肿囊壁中阳性表达率分别为59．38％、66．67％、20．00％,Livin在牙源性角化囊性瘤中的阳性表达率高于含牙囊肿（P＜0．05）,牙源性角化囊性瘤中Bcl-xL与Livin的表达呈正相关（r＝0．483,P＜0．05）。结论：Bcl-xL、Livin在牙源性角化囊性瘤的发生发展中可能起一定作用,并且二者可能具有协同效应。     

Differences in collagen fibres in the capsule walls of parakeratinized and orthokeratinized odontogenic cysts

Epithelial-mesenchymal interactions are thought to play an important role in the pathogenesis of odontogenic lesions. Keratocystic odontogenic tumour (KCOT) is a benign cystic neoplasm with a characteristic parakeratinized epithelial lining, which differs histologically and behaviourally from the so-called orthokeratinized odontogenic cyst (OOC). The purpose of this study was to investigate the differences in collagen fibres within the fibrous tissue walls of KCOT and OOC. Formalin-fixed paraffin-embedded tissue samples from 15 cases of KCOT and 15 cases of OOC were collected. Paraffin sections were stained with picrosirius red and observed under a standard light microscope using optical polarization. Unicystic ameloblastoma (UA, 15 cases) and subcutaneous epidermoid cysts (EC, 15 cases) were included in the study for comparative purposes. Significant difference was detected between the polarization colours in the fibrous tissue walls of KCOT and OOC (P < 0.05), whilst no significant differences were found between KCOT and UA and between OOC and EC (P > 0.05). The stromal collagen fibres of KCOT were different from those of OOC, but similar to those of UA, which suggests that the stroma of KOCT may play an important role in determining the neoplastic behaviour of the lesion through epithelial-mesenchymal interaction.     

Co-expression of Ki-67 and p53 protein in ameloblastoma and keratocystic odontogenic tumor

Abstract

Objectives. The purpose of this study was to evaluate the cell proliferation and p53 protein expression in ameloblastomas (ABs), keratocystic odontogenic tumor (KCOT) and dentigerous cyst (DC). Method. The immunohistochemistry were carried out for Ki-67 and p53 protein expression by using MIB-1 clone and DO-7 clone, respectively, in ABs (n = 23), KCOT (n = 32), DC (n = 30), normal oral mucosa (NOM) (n = 12) and fetal oral mucosa (FOM) (n = 10). Results. Both the Ki-67 LI Labeling index (LI) and p53 LI was significantly higher in ABs than KCOT, DC, NOM and FOM. The Ki-67 LI and p53 LI was significantly higher in KCOT as compared to DC. Ki-67 LI and p53 LI was observed in descending order in ABs, KOCT, FOM, NOM and DC. There was significant correlation between Ki-67 expression and p53 expression in ABs, KCOT, DC and NOM. The densely stained p53 positive cells were noted higher in ABs than KCOT. The very few densely p53 positive cells were noted in DC, NOM and FOM. Conclusion. The results suggest that the p53 protein expression does not necessarily imply an association with malignant disease and/or p53 gene mutation, but a tendency to be expressed in an increasing quantitative and qualitative manner, as the biologic behavior of odontogenic cyst or tumors becomes more aggressive. p53 over-expression may promote cell proliferation in odontogenic lesions. Thus, it can be stipulated that Ki-67 and p53 protein expression can be used as a prognostic marker in odontogenic lesions.     

Multicentric familial squamous odontogenic tumor

Three cases of multicentric squamous odontogenic tumor, one of which was previously reported, are presented in three black siblings. A review of the literature indicates that 5 of the 26 previously recorded cases arose in multiple sites, but no evidence of familial history has been suggested. Although squamous odontogenic tumor has been described as a relatively rare, benign odontogenic neoplasm, the multicentric familial nature of our present cases suggests this represents either a reactive hyperplasia or hamartoma of residual odontogenic epithelium within the periodontal tissues. Management of previous cases has varied from simple curettage to maxillectomy with only one case of recurrence.