Expression of Bcl-2 in Primary and Recurrent Odontogenic Keratocysts in Comparison with Other Odontogenic Lesions.

PURPOSE: To determine the biological behaviour of common odontogenic cystic lesions by analysing and comparing bcl-2 expression amongst them. MATERIALS AND METHODS: Our study covered 90 formalin fixed paraffin embedded tissue samples: 26 primary cases each of radicular cysts (RC), dentigerous cysts (DC) and odontogenic keratocysts (OKC) and 12 of recurrent OKCs. Bcl-2 expression was analysed immunohistochemically and data analysis was accomplished using SPSS version 17.0. Means were taken for age while for gender and site of the lesions frequencies and percentages were determined. The Chi-square test was applied to evaluate any statistically significant difference of bcl-2 expression in these lesions and p value of ≤0.05 was taken as significant. RESULTS: All the recurrent OKCs showed a strong positivity for bcl-2 that was absent in all of its primary cases (p value<0.05). Although variation in expression of bcl-2 was not found to be statistically significant between RC and DC, however, it became significant when all primary cases of these common odontogenic lesions were compared. CONCLUSIONS: Recurrent OKC showed comparatively a more aggressive behaviour than their primary counterparts and also from RC and DC. Bcl-2 proved to be a valuable adjunct in determining aggressive biological behaviour of odontogenic lesions.

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.

Immunohistochemical analysis of CK 18 in dental follicles of impacted third molars: a pilot study.

OBJECTIVE: Odontogenic tumors are lesions derived from epithelial, ectomesenchymal, and/or mesenchymal elements that still are, or have been, part of the tooth-forming apparatus. Approximately 80% of odontogenic tumors occur in the mandible, with a marked predilection for the posterior region, and are often associated with an unerupted tooth. The aim of this study was to determine whether cytokeratin (CK) 18 immunostaining decorated the follicular tissue removed at the time of prophylactic extraction of impacted mandibular third molars, which might suggest oncofetal transformation. MATERIALS AND METHODS: Fifty-four impactions met the study inclusion criteria, of which 24 cases showed the presence of reduced enamel epithelium and/or connective tissue with odontogenic epithelium, which were subjected to CK 18 immunostaining. RESULTS: All 24 cases with adequate epithelium were CK 18 immunonegative. CONCLUSION: There was no oncofetal transformation in the odontogenic epithelia of the dental follicles studied. Thus, although we reaffirm that evaluation of follicular tissue is imperative since disease conditions may be found in minute follicular spaces, development of odontogenic cysts and tumors is unlikely.

Cyclin d1 expression in odontogenic cysts.

OBJECTIVE: In the present study expression of cyclin D1 in the epithelial lining of odontogenic keratocyst, radicular cyst, dentigerous cyst and glandular odontogenic cyst was investigated to compare proliferative activity in these lesions. MATERIAL AND METHOD: Immunohistochemical staining of cyclin D1 on formalin-fixed, paraffin-embedded tissue sections of odontogenic keratocysts (n=23), dentigerous cysts (n=20), radicular cysts (n=20) and glandular odontogenic cysts (n=5) was performed by standard EnVision method. Then, slides were studied to evaluate the following parameters in epithelial lining of cysts: expression, expression pattern, staining intensity and localization of expression. RESULTS: The data analysis showed statistically significant difference in cyclin D1 expression in studied groups (p < 0.001). Assessment of staining intensity and staining pattern showed more strong intensity and focally pattern in odontogenic keratocysts, but difference was not statistically significant among groups respectively (p=0.204, 0.469). Considering expression localization, cyclin D1 positive cells in odontogenic keratocysts and dentigerous cysts were frequently confined in parabasal layer, different from radicular cysts and glandular odontogenic cysts. The difference was statistically significant (p < 0.01). CONCLUSION: Findings showed higher expression of cyclin D1 in parabasal layer of odontogenic keratocyst and the entire cystic epithelium of glandular odontogenic cysts comparing to dentigerous cysts and radicular cysts, implying the possible role of G1-S cell cycle phase disturbances in the aggressiveness of odontogenic keratocyst and glandular odontogenic cyst.

Cystinosis, Fanconi syndrome, and odontogenic cysts.

Cystinosis is a multisystemic genetic storage disorder characterized by a mutation in the transporter system of cystine. The disease particularly affects the renal system by causing deposition of cystine crystals leading to, if untreated, Fanconi syndrome and end-stage renal disease. This disease also affects the ocular system, central nervous system, endocrine system, hepatobiliary system, and musculoskeletal system. We present the first case of cystine crystal deposition within an odontogenic cyst, confirmed by the correlation of the clinical, radiographic, and histologic findings on this patient.

Immunohistochemical profile of integrins in enlarged dental follicles and dentigerous cysts.

OBJECTIVE AND STUDY DESIGN: The morphological distinction between incipient dentigerous cyst (IDC) and enlarged pericoronal dental follicle (EDF) remains one of the most controversial questions in the literature. The objective of this study was to analyze the immunohistochemistry expression of alfa(2)beta(1), alfa(3)beta(1), and alfa(5)beta(1) in 23 cases of EDFs and 21 cases of IDCs. RESULTS: All integrins were immunopositive in the cases studied. A significant difference was detected regarding alfa(2)beta(1) integrin (P < .0001) in which a higher expression was present in IDCs. Moreover, statistical difference was also found between basal and suprabasal cell layer in cystic epithelium (P < .0034). The alfa(3)beta(1) integrin expression showed significant difference (P < .013) between EDF and IDC with a tendency of more pronounced staining in IDC. CONCLUSIONS: These results corroborate the possibility of histopathological distinction between EDF and IDC in which squamous metaplasia of reduced enamel epithelium to stratified epithelium would be the first event of cystic transformation.

Immunohistochemical analysis of the biological potential of odontogenic keratocysts.

BACKGROUND: The aim of this study was to analyse the usefulness of detecting important apoptosis and proliferation markers in assessing the biological potential of odontogenic keratocysts (OKC) and thus selecting the optimal diagnostic algorithm for these lesions. METHODS: Indirect immunohistochemistry and relevant statistical methods were used for analysis of formalin-fixed and paraffin-embedded samples from 98 patients. RESULTS: Nevoid basal cell carcinoma syndrome (NBCCS) keratocysts were characterized by higher expression of Bcl-2, p27Kip1 and c-erbB-2 as well as by lower proliferative activity measured by Ki-67 in basal cell epithelium and by a lower inflammatory response in comparison with sporadic keratocysts. Dentigerous, radicular and non-specified odontogenic cysts differed from both NBCCS and sporadic keratocysts in a wide spectrum of apoptosis and/or cell cycle-related protein expressions, higher proliferation in the basal cell layer, and vice versa, lower proliferation in the suprabasal cell layer. CONCLUSIONS: The NBCCS keratocysts have a different immunophenotype from sporadic keratocysts and both types are distinguishable from dentigerous, radicular and non-specified odontogenic cysts. These findings confirm the separate biological potential of these lesions and the results of the immunohistochemical analysis have diagnostic and prognostic implications.

The differential expression pattern of BMP-4 between the dentigerous cyst and the odontogenic keratocyst.

BACKGROUND: Bone morphogenic protein-4 (BMP-4) is widely expressed in oral cavity and involved in tooth morphogenesis, cellular differentiation and proliferation. The purpose of this study was to compare the difference in expression pattern of BMP-4 in odontogenic keratocysts (OKC) and dentigerous cysts (DC). METHODS: We evaluated 77 cysts, OKC (n = 34) or DC (n = 43). The average age of patients with OKC was 29.5 +/- 14.4 and that of patients with DC was 36.1 +/- 19.4. The male to female ratio was 20:14 for OKC and 27:16 for DC. Ten cases of OKC were recurrences. Expression of BMP-4 was determined by immunohistochemistry and in situ hybridization. RESULTS: The intensity scales were (-) for invisible or trace staining, (+) for visible staining, and (++) for dense, strong staining. OKCs exhibited the following staining patterns: the epithelium in 15/34 specimens and the mesenchymal cells in 17/34 specimens showed (++) stain. In contrast, the staining pattern of DC was (-) for epithelium in 37/43 specimens. The mesenchymal cells showed (-) degree staining in 30/43 specimens. The difference between the groups studied was significant (P < 0.001 in epithelium and mesenchymal cells). When recurrent and non-recurrent OKC were compared BMP-4 was expressed more intensely in the recurrent cases (P = 0.036 in epithelium). The difference in BMP-4 expression in mesenchymal cells was not significant. In situ hybridization demonstrated positive mRNA probes to BMP-4 were localized in epithelium and mesenchymal cells of OKCs and DCs. CONCLUSIONS: BMP-4 was expressed more intensely in OKC when compared with DC, and was more intensely expressed in recurrent cases.

Case report of a pigmented dentigerous cyst and a review of the literature on pigmented odontogenic cysts.

This paper reports the first case of a dentigerous cyst containing melanin-pigment and melanocytes in the lining epithelium, and the first case of a odontogenic cyst with macroscopically visible pigmentation in the cyst wall. The patient was a 29-year-old Japanese male with a cystic lesion in the left retromolar area of the mandible. Pathologic examination revealed the lesion to be a dentigerous cyst with or without mild surface keratinization, and numerous granules of melanin-pigment were distributed in the basal cells of the epithelial lining. Furthermore, dendritic melanocytes were scattered in the basal layer. Review of the literature revealed that pigmented odontogenic cysts are uncommon, and only 11 cases have been documented; eight were odontogenic keratocyst, one was a gingival cyst, one was a botryoid odontogenic cyst, and one was a lateral periodontal cyst. The possible origin of melanocytes in odontogenic lesions is discussed.

Immunohistochemical study of bcl-2 protein, Ki-67 antigen and p53 protein in epithelium of glandular odontogenic cysts and dentigerous cysts.

The aim of the present study was the evaluation of the immunohistochemical expression of the apoptosis-inhibiting protein bcl-2, the cell-cycle-related antigen Ki-67 and the p53 protein, which is involved both in cell cycle and apoptosis regulation, in the lining epithelium of glandular odontogenic cysts of the jaws. Formalin-fixed and paraffin-embedded tissue sections of three glandular odontogenic cysts and six dentigerous cysts were immunostained with a standard avidin-biotin peroxidase procedure, after microwave antigen retrieval. The glandular odontogenic cysts showed immunoreactivity for bcl-2 protein in the basal and suprabasal layers, while staining in dentigerous cysts was basal or focal. Most mucous cells and superficial cuboidal cells were negative. The percentage of Ki-67- or p53-positive cells was lower in glandular odontogenic cysts compared with dentigerous cysts. The findings suggest that the biological behavior of glandular odontogenic cysts may be associated with deregulation of cell death in the lining epithelium, while cell proliferation and p53 status do not seem to play a significant role.

Immunocytochemical expression of parathyroid hormone related protein (PTHrP) in odontogenic jaw cysts.

OBJECTIVE: To investigate the immunocytochemical expression of parathyroid-hormone-related protein (PTHrP) in odontogenic jaw cysts. DESIGN: Retrospective study of archival tissue. SETTING: University department, UK. MATERIAL: Odontogenic keratocysts (n=27), and dentigerous and radicular cysts (n=10 each). INTERVENTION: Immunocytochemistry by biotin streptavidin technique. MAIN OUTCOME MEASURE: Intensity of staining of PTHrP determined by TV image analysis. RESULTS: The epithelial linings of all the odontogenic keratocysts, 9/10 dentigerous, and 8/10 radicular cysts showed reactivity for PTHrP mainly localised to the basal and suprabasal layers. Odontogenic keratocyst linings expressed significantly higher levels of PTHrP than those of dentigerous and radicular cysts (P<0.003 in each case). There were no differences in epithelial expression of PTHrP between solitary, recurrent and naevoid basal cell carcinoma syndrome-associated odontogenic keratocysts. The fibrous tissue walls of all types of cyst reacted strongly for PTHrP with a trend towards decreasing intensity from odontogenic keratocysts, to dentigerous and then radicular cysts. CONCLUSION: It is possible that PTHrP modulates growth and bone resorption in odontogenic cysts. PTHrP may act synergistically with interleukin-1 to increase bone resorption or stimulate osteoblasts and inhibit osteoclasts (resulting in reduced resorption) via its transforming growth factor beta-like activity.

Immunohistochemical study on proliferating cell nuclear antigen expression in ameloblastomas.

The aim of this study is to evaluate the proliferating activity of ameloblastomas and its correlation to the biological behaviour according to each histological type. 38 cases of solid and unicystic ameloblastomas were reviewed including 1 case of ameloblastic carcinoma and 1 recurrent case. An anti-PCNA antibody, PC10(Dako), was applied for the detection of proliferating cell nuclear antigen (PCNA) in paraffin embedded tissue sections. Also 20 cases of dentigerous cysts were reviewed. In conclusion, we observed that there was no difference between the proliferating activities of the different histological types of solid ameloblastomas. Because 1 case of ameloblastic carcinoma and one recurrent case revealed remarkably high PCNA reactivity, we believe that PCNA would be useful in showing the differentiation between benign and malignant ameloblastomas. In unicystic ameloblastomas, plexiform intraluminal growth was considered to be an important feature in tumorous transformation of cystic epithelium.

Estudo imunocitoquímico comparativo dos folículos pericoronários, cistos dentígeros e queratocistos odontogênicos / Immunohistochemical comparative study of the dental follicles with dentigerous cysts and odontogenic keratocysts

Com o objetivo de estabelecer as características imunocitoquímicas de folículos pericoronários, cistos dentígeros e queratocistos odontogênicos, foram selecionados dos arquivos do Laboratório de Anatomia Patológica do Departamento de Patologia da Faculdade de Odontologia de Bauru USP, dez casos de folículos pericoronários com epitélio reduzido do orgäo do esmalte, dez casos de folículos pericoronários com metaplasia escamosa, dez casos de cistos dentígeros e dez casos de queratocistos odontogênicos, submetidos a evidenciaçäo imunocitoquímica de um painel constituído dos seguintes marcadores: citoqueratina de alto peso molecular, citoqueratina de baixo peso molecular, laminina, fibronectina, colágeno IV, vimentina e proteína S100. A partir dos resultados obtidos pudemos concluir que o padräo imunocitoquímico das 4 condiçöes estudadas permite uma diferenciaçäo diagnóstica entre folículos pericoronários, cistos dentígeros e queratocistos odontogênicos, utilizando-se a marcaçäo da proteína S100. A diferenciaçäo pela marcaçäo com a proteína S100 pode ser complementada pela evidenciaçäo das células de Langerhans, que caracteristicamente estäo presentes nos revestimentos epiteliais dos cistos dentígeros

The nature of ghost cells in calcifying odontogenic cyst: an immunohistochemical study.

Two solid and two cystic forms of calcifying odontogenic cysts were stained immunohistochemically to study keratin, carcinoembryonic antigen, epithelial membrane antigen, and S-100 protein expression in ghost cells. The patterns of immunoreactivity were compared with those of dentigerous cysts, odontogenic keratocysts, ameloblastomas, calcifying epitheliomas of Malherbe, and control samples. Immunostaining patterns of calcifying odontogenic cysts were found to be similar to the odontogenic lesions and different from calcifying epithelioma. It is concluded that ghost cells are "keratinizing" odontogenic cells showing aberrant differentiation. These cells should not be regarded as metaplastic. The similarity of the immunostaining patterns of cystic and solid calcifying odontogenic cysts supports the view that these lesions are two morphologic variants of the same entity.

Lectin histochemistry of cystic jaw lesions: an aid for differential diagnosis between cystic ameloblastoma and odontogenic cysts.

The binding sites for Ulex europaeus agglutinin I (UEA-I), Bandeirea simplicifolia agglutinin I (BSA-I), and peanut agglutinin (PNA) were comparatively examined in the surgical materials from 41 cases of cystic and solid ameloblastomas and 42 cases of non-neoplastic odontogenic cysts including dentigerous cyst, odontogenic keratocyst, and radicular cyst. In non-neoplastic cysts, most of epithelial lining layers gave positive binding with UEA-I and BSA-I. However, no positive reactions were obtained for these two lectins in the epithelial components of ameloblastoma, except for limited UEA-I binding to markedly keratinized tumor cells in four cases. PNA binding was irregular and did not make any clear distinction between ameloblastomas and cysts. The results suggest that the lectin staining for UEA-I and BSA-I is a useful histologic aid for differential diagnosis between cystic ameloblastoma and non-neoplastic jaw cysts.

Immunohistochemical study of jaw cysts: different existence of keratins in odontogenic and non-odontogenic epithelial linings.

Keratins and secretory component (SC) were immunohistochemically examined in fresh tissue samples from 45 odontogenic and 35 non-odontogenic cysts. Lining epithelia of almost all cases contained keratins which reacted with polyclonal antibodies (Dako, Bio-Science), and no difference could be found between the two groups of lesions. By staining with two monoclonal antibodies against keratins, i.e., RGE53 (Bio-Science) and RKSE60 (Bio-Science), it was revealed that the epithelia of non-odontogenic cysts, which were columnar epithelium in most cases, had fully and positively reacted with RGE53, while none of the cases was positive for RKSE60. In contrast, the squamous linings of odontogenic cysts except for two cases did not react with RGE53, and few cases possessed RKSE60-reactive keratin. SC was also contradictory. All non-odontogenic cysts exhibited SC. Regarding each pair of non-odontogenic and odontogenic cysts covered with RGE53 and SC-positive, and RKSE60-negative squamous epithelium, it seemed reasonable from the staining results to conclude that the squamous linings were metaplastic from the columnar epithelium. Based on the results, concomitant examinations of SC with keratins will be helpful in deciding the epithelial derivation of jaw cysts.