Cytokeratin expression patterns for distinction of odontogenic keratocysts from dentigerous and radicular cysts

BACKGROUND: The clinical outcome of treatment of odontogenic cysts differs depending on separate entities. Particular clinical relevance must be attached to the distinction between odontogenic keratocysts, which have an evident tendency to recur, and other odontogenic cysts. The aim of this study was to evaluate cytokeratin (CK) expression patterns as an additional tool for characterization of different cysts as the histomorphologic appearance often is not decisive. METHODS: Thirty cases of dentigerous and radicular cysts respectively as well as 15 cases of odontogenic keratocysts were considered. Expression of CK 5/6, 7, 10, 13, 17, 19 and 20 was determined in addition to Ki-67 immunohistochemically. RESULTS: Expression of CK 17 was discernible in 93.3% of the odontogenic keratocysts, but only in 35.0% of dentigerous and radicular cysts under study (P < 0.001). CK 19 could be detected in 48.3% of dentigerous and radicular cysts, whereas odontogenic keratocysts were completely negative (P < 0.002). CONCLUSION: Immunohistochemical detection of CK 17 and 19 seems to be a valuable additional parameter distinguishing between odontogenic keratocysts and other odontogenic--especially dentigerous--cysts which clinically are likely the most significant differential diagnoses in this context. J Oral Pathol Med (2005) 34: 558-64.     

Comparative immunohistochemical expression of RANK, RANKL and OPG in radicular and dentigerous cysts

Objective

Receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG) are members of the superfamily of ligands and receptors of tumour necrosis factor family involved in bone metabolism. The formation, differentiation and activity of osteoclasts are regulated by these proteins. To clarify the roles of osteoclast regulatory factors in cystic expansion of odontogenic cysts, expression of these proteins were analysed in radicular and dentigerous cysts.

Design

The immunohistochemistry expression of these biomarkers were evaluated and measured in lining epithelium and fibrous capsule of the radicular (n = 20) and dentigerous cysts (n = 20).

Results

A similar expression in lining epithelium was observed in the lesions. The fibrous capsule of dentigerous cyst showed a higher content of RANK-positive and RANKL-positive cells than fibrous capsule of radicular cyst. In the lining epithelium the RANKL/OPG ratio showed higher numbers of OPG-positive than RANKL-positive cells, whereas fibrous capsule of the cysts had a tendency to present a similar expression (OPG = RANKL).

Conclusion

Ours findings indicate the presence of RANK, RANKL and OPG in cysts. Moreover, increased expression of OPG compared to RANKL in the lining epithelium could contribute to the differential bone resorption activity in theses lesions.     

Immunohistochemical detection of factors related to cellular proliferation and apoptosis in radicular and dentigerous cysts

Introduction

This study proposed to investigate aspects of cell proliferation and death in the epithelium of radicular (RCs) and dentigerous (DCs) cysts.

Methods

Serial sections of 17 RCs and 9 DCs were prepared for immunohistochemical detection of caspase-3, Bcl-2, and Ki-67 antigens.

Results

Caspase-3 was detected mainly in the suprabasal and superficial epithelial cells of RCs and DCs, whereas Ki-67 was detected predominantly in the basal layer. Both markers had significant expression in hyperplastic epithelium related to an intense inflammation in the capsule. Immunoreactivity for Bcl-2 was restricted to the basal layer and was significantly higher in atrophic epithelium of DCs than that of RCs.

Conclusions

These results suggest that epithelial proliferation is balanced by apoptosis and that the presence of inflammation inhibits the Bcl-2 expression. DCs and RCs have different formation mechanisms but have similar biological behavior in the presence of intense inflammatory infiltrate.     

Comparison of angiogenesis in keratocystic odontogenic tumours, dentigerous cysts and ameloblastomas

Objective:  The aim of the present study was to evaluate and compare angiogenesis in keratocystic odontogenic tumours, dentigerous cysts (DCs) and ameloblasomas using monoclonal antibody against CD34.
Materials and methods:  Microvessel density was assessed in a total of 53 cases including 20 keratocystic odontogenic tumours, 13 DCs and 20 ameloblastomas (14 solid and six unicystic variants). Microvessel density was expressed as the mean number of microvessels per high-power-field.
Results:  Statistically significant differences in mean microvessel density were observed between keratocystic odontogenic tumours, DCs and solid ameloblastomas ( P  < 0.001). Mean microvessel density was significantly higher in solid ameloblastomas compared with both keratocystic odontogenic tumours and DCs; and was also significantly higher in keratocystic odontogenic tumours than in DCs.
Conclusion:  Within the limitations of the present study, it can be suggested that angiogenesis may be one of the mechanisms possibly contributing to the different biological behaviours of keratocystic odontogenic tumours, DCs and solid ameloblastomas.     

669例牙源性颌骨囊肿临床分析

目的 :比较角化囊肿、根端囊肿、含牙囊肿等三型牙源性颌骨囊肿的临床特点。方法 :收集 2 0年间牙源性角化囊肿 (odontogenickeratocyst,OKC)、根端囊肿 (radicularcyst ,RC)及含牙囊肿 (dentigerouscyst ,DC)的临床资料 ,对其性别构成、年龄分布、发病部位及临床表现等进行比较研究。结果 :①三型颌骨囊肿的男女之比分别为 :OKC 1.6∶1,RC 1.4∶1,DC 4.1∶1(x2 检验 ,P <0 .0 0 5 )。②除DC未见于 70岁以上年龄段外 ,几乎各年龄段均见三型颌骨囊肿的发生 ,三型囊肿组间及组内的年龄分布均有显著性差异 (x2 检验 ,P <0 .0 0 5 )。OKC及RC 2 0～ 2 9岁年龄段患病人数最多 ,分别占各年龄段患病人数的 2 7%及 2 0 % ;DC 10～ 19岁年龄段患病人数最多 ,占各年龄段患病人数的 2 9%。③颌骨的任一部位均见三型颌骨囊肿的发生 ,但发生频率不同 ,三型颌骨囊肿组间及组内发病部位的分布有显著性差异 (x2 检验 ,P <0 .0 0 5 )。OKC以下颌磨牙区发生率最高 ( 5 5 % ) ,其次为下颌前磨牙区( 4 1% ) ;RC及DC则以上颌前牙区发生率最高 ,二者的发生率分别为 5 7%与 75 %。④OKC有 13 7例合并感染 ,感染率 3 9% ;RC 48例合并感染 ,感染率 2 4% ;DC 18例合并感染 ,感染率 16% ,三型间有显著性差异 (x2 检验 ,P <0 .0 0 5     

Tenascin and fibronectin expression in odontogenic cysts

BACKGROUND: Odontogenic cysts (OCs) present distinct evolution and clinical behavior. This study was performed in order to investigate if some components of the extracellular matrix (ECM) may drive these differences. METHODS: Thirty OCs were selected: 10 radicular cysts (RCs), 10 dentigerous cysts (DCs), 10 non-syndrome odontogenic keratocysts (OKCs) and they were immunohistochemically analyzed to verify the expression pattern of tenascin and fibronectin. RESULTS: Tenascin immunostaining was mainly intense as a thick band deep to the epithelial-mesenchymal interface in both RCs and OKCs. The intense tenascin immunoexpression observed in the RCs was usually associated with inflammation. An intense fibronectin reactivity was observed in the basement membrane region and at the cystic wall of OKCs. CONCLUSIONS: Our results demonstrate differences between the expression of ECM proteins in the OCs studied. The higher tenascin and fibronectin expression in the capsule of OKCs suggests marked instability in the cystic structure and may contribute to its aggressive behavior.     

Squamous odontogenic tumor-like proliferations in radicular cysts: a clinicopathologic study of forty-two cases

Introduction

Squamous odontogenic tumor-like epithelial islands occurring in the walls of odontogenic cysts are histologically identical to the squamous odontogenic tumor (SOT). Microscopically, the squamous odontogenic tumor-like proliferations (SOTLPs) share certain histologic features with SOT, acanthomatous and desmoplastic ameloblastoma, and well-dif-ferentiated squamous cell carcinoma. Little is known about the rarely reported SOTLPs occurring in radicular cysts. The purpose of this study was to define the clinical and histopathologic spectrum of SOTLP in radicular cysts and to investigate its histogenesis, prevalence, and biologic behavior.

Methods

A retrospective clinicopathologic study was conducted at the Louisiana State University School of Dentistry, and a total of 42 radicular cysts with SOTLPs were accepted. Clinical findings and detailed histopathologic features were documented, and follow-up information was solicited for the 42 cases.

Results

Forty-two cases of radicular cysts with SOTLPs were found among 1241 radicular cysts. Two thirds of the cases revealed the SOTLPs were arising from budlike extensions of the epithelial lining of the cyst. The SOT-like epithelial islands were in areas free of inflammatory cells in 73.8% of the cases. No evidence of recurrence or unexpected clinical behavior was reported in 11 cases with adequate follow-up.

Conclusions

The prevalence of SOTLPs in radicular cysts at Louisiana State University School of Dentistry is 3.4%. The SOTLPs appear to originate from the epithelial lining of the cyst and do not appear to be directly associated with inflammation. The biologic behavior of the radicular cyst with SOTLP is innocuous, with no apparent potential for neoplastic transformation or recurrence.     

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.     

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.     

A comparative stereologic and ultrastructural study of blood vessels in odontogenic keratocysts and dentigerous cysts

Blood vessels were investigated both stereologically and ultrastructurally in keratocyst and dentigerous cyst. The volume and surface densities of blood vessels in 15 keratocysts and dentigerous cysts were analyzed stereologically. No significant differences were found between them using these parameters, suggesting that their overall vascularity may be similar. However, the ultrastructural study showed marked differences between blood vessels in these two types of cysts. It was observed that fenestrated capillaries were found only in keratocysts. In addition, degeneration of endothelial lining associated with thrombosis was also a prominent feature of this cyst. While ruptured endothelium, narrow lumen and Weibel-Palade bodies were characteristic of vessels in dentigerous cyst. The presence of fenestrated capillaries in keratocyst and not in dentigerous cyst might indicate a rapid transfer of fluid to meet the demand of the relatively active proliferating epithelium, which may be promoted by growth factors released from platelets in those thrombosed vessels.     

Evaluation of mast cells in periapical cysts, dentigerous cysts, and keratocystic odontogenic tumors

J Oral Pathol Med (2012) 41 : 630–636 Background: Several cell types are associated with the development of cystic and tumoral odontogenic lesions. Among inflammatory cells, mast cells can be associated with their pathogenesis. The aim of this study was to analyze mast cells in periapical cysts, dentigerous cysts, and keratocystic odontogenic tumors. Methods: Tissue sections were submitted to toluidine blue staining and immunohistochemistry with antibody anti‐tryptase (clone G3). Mast cells were quantitated using Image‐Pro Plus software to obtain the mean number of mast cells in three regions: epithelial, superficial portion of the fibrous wall and deep portion of the fibrous wall from 20 periapical cysts, 20 dentigerous cysts (six non‐inflamed and 14 inflamed) and 20 keratocystic odontogenic tumors (four non‐inflamed and 16 inflamed). Results: The mean number of mast cells detected per lesion by immunohistochemistry (4.1) was higher than by histochemistry (1.5) (P < 0.0001). Inflamed dentigerous cysts and keratocystic odontogenic tumors showed a higher mean number of mast cells than non‐inflamed lesions in all regions. The deep region from all cysts showed the highest mean number of degranulated mast cells, except for non‐inflamed keratocystic odontogenic tumors analyzed by immunohistochemistry. Conclusions: Immunohistochemical staining detected higher number of mast cells than histochemistry. The higher number of mast cells observed in inflamed lesions could indicate the participation of these cells in the inflammatory response in odontogenic lesions. The prevalence of degranulated mast cells in the deep region suggests intense activity of these cells, possibly related to growth of cystic lesions.     

A comparative study of epithelial cell proliferation between the odontogenic keratocyst, orthokeratinized odontogenic cyst, dentigerous cyst, and ameloblastoma

OBJECTIVES: The aim of the present study was to compare the proliferation index of the epithelial cells between odontogenic keratocysts (OKC), orthokeratinized odontogenic cysts (OOC), dentigerous cysts (DC), and ameloblastomas. MATERIALS AND METHODS: The proliferation index, employing a novel cell proliferation marker IPO-38, was studied by the immunohistochemical technique in 10 OKC, seven OOC, eight DC and 10 ameloblastomas. RESULTS: The ameloblastoma had no higher labeling index (LI) of IPO-38 than the OKC (P = 0.910) but had higher LI than the OOC (P = 0.001) and DC (P = 0.000); the OKC had higher LI than the OOC (P = 0.002) and DC (P = 0.000); and the OOC had higher LI than the DC (P = 0.011). IPO-38-positive cells in the OKC and OOC were located principally in the suprabasal cell layers while the ameloblastoma were found in the peripheral portion in particularly, the follicular and plexiform types. CONCLUSION: These findings support previous studies that the proliferation indices are useful in predicting the different biological behavior of the odontogenic lesions and the OKC should be regarded as a benign tumor rather than simply an odontogenic cyst.     

Cell proliferation, apoptosis and apoptosis-related factors in odontogenic keratocysts and in dentigerous cysts

BACKGROUND: The purpose of this study was to elucidate why odontogenic keratocysts (OKC) can form cystic lesions but not tumor masses, notwithstanding their prominent proliferative activity. METHODS: We investigated cellular proliferation, cell death, and expression of apoptosis-related proteins in the lining cells of OKCs and of dentigerous cysts (DGCs). RESULTS: TdT-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells were observed in the surface layers of OKCs and of DGCs. However, no TUNEL-positive cells were seen in the basal or intermediate layers of both cysts. Ki67-positive ratio in the intermediate layer was the highest in OKCs. The p53-positive ratio of the intermediate layer was highest in OKCs. Bcl-2-positive cells were discernible exclusively in the basal layer of OKCs. CONCLUSIONS: These results suggest that cellular proliferation and death is regulated in association with apoptosis-related proteins in the lining epithelia of OKCs, and subsequently those cysts are seen as cystic lesions but not as tumor masses.     

PTCH gene altered in dentigerous cysts

Motivated by the evidence that odontogenic keratocysts are associated with genetic alterations, we examined the possibility that development of other odontogenic cysts can be attributed to gene malfunctioning, in particular to the PTCH gene. Cyst epithelium was examined for polymorphism on chromosome 9q22.3, the region that contains the PTCH gene. Loss of heterozygosity (LOH) for the D9S287 marker and/or D9S180 marker was observed in about 50% of dentigerous cysts, whereas radicular cysts gave no indication of lesions in the PTCH region. As a more direct argument for PTCH involvement in cystic growth, we report evidence of PTCH expression in dentigerous cyst lining, which indicates malfunctioning of the relevant signaling pathway. While we found no reason to believe that PTCH should be associated with radicular cysts, other genes may be implicated in their development. We performed immunohistochemical comparisons of keratocysts, dentigerous and radicular cysts for the nonmetastatic marker Nm23. A graded response placed radicular cysts in between the other two types, suggesting a similar neoplastic character for their epithelial proliferation.     

Alterations of FHIT and P53 genes in keratocystic odontogenic tumor, dentigerous and radicular cyst

Background:  The purpose of this study was to determine fragile histidine triad (FHIT) and p53 protein expression, and to analyze FHIT and p53 gene status in keratocystic odontogenic tumor (KOT), dentigerous cysts (DC) and radicular cysts (RC).
Methods:  The methods used were immunohistochemistry and molecular genetic methods including loss of heterozygosity (LOH) and gene sequencing.
Results:  FHIT protein expression was different among groups. Aberrant expression was the highest in KOT, then in RC and DC. p53 protein expression was different among groups. LOH in paraffin-embedded specimens was detected in 22.6% and 12.9% for FHIT and p53 respectively. Mutation of p53 gene at codon 237 was observed in only two specimens (one KOT and one DC). Of the six frozen specimens, three exhibited FHIT gene LOH (two RC and one KOT). KOT showed loss of exons 6–7 at FHIT locus and mutation at codon 237 at p53 locus, but this could be a chance result.
Conclusion:  Aberrations of FHIT and p53 genes/proteins could be considered markers responsible for the development of odontogenic lesions.     

Age-standardized incidence rates of ameloblastoma and dentigerous cyst on the Witwatersrand, South Africa

Although a great deal is known about the incidence of cancer, including oral cancer, no such study has been done on odontogenic tumors and jaw cysts. There are therefore no standardized data which would allow for comparative incidences in different countries and between different groups. In the present study, cases of ameloblastomas and dentigerous cysts derived from the records of all the hospital pathology departments and private pathology practices on the Witwatersrand, were recorded for the 10-year period 1965--1974. The population at risk (1970 census) was 974,390 Whites and 1,567,280 Blacks. The annual incidence rates, standardized against the standard world population, for ameloblastomas per million population are 1.96, 1.20, 0.18 and 0.44 for Black males, females and White males, females, respectively. The equivalent four figures for dentigerous cysts are 1.18, 1.22, 9.92 and 7.26. These figures show that ameloblastoma is very much more common in Blacks than Whites in the population at risk. Conversely, dentigerous cysts are much more common in Whites. This makes it unlikely that dentigerous cysts predispose to ameloblastoma formation. These epidemiologic observations give rise to speculation as to whether some component of the South African Black diet or other environmental substance might possibly be an etiologic factor in ameloblastoma.     

Apoptosis in epithelial cells of apical radicular cysts

AIM: To investigate the occurrence of apoptotic cell death in the epithelium of radicular cysts and to compare its frequency in lesions presenting a distinct functional state. METHODOLOGY: Twenty radicular cysts were selected and arranged into two groups with 10 lesions in each group: atrophic (quiescent) and hyperplastic (active) epithelium. Morphologic investigations of apoptosis were conducted by means of optic microscopy in haematoxylin and eosin slides. Immunohistochemical techniques to detect the bcl-2 protein were carried out by streptavidin-biotin-peroxidase assay. In both instances, 30 sequential high-power microscopic fields were observed to determine apoptotic (AI) and bcl-2 immunostaining (bcl-2I) indexes. The presence of AI and bcl-2I within the two groups was compared using the t-test. Correlation between the AI and the bcl-2I was investigated using the Spearman test. RESULTS: Apoptosis was detected in the epithelium of all cysts. Higher AI levels were found in lesions with an atrophic (0.17 +/- 0.19) rather than a hyperplastic (0.10 +/- 0.10) epithelium. The same was found for the bcl-2I levels (0.06 +/- 0.03 vs. 0.04 +/- 0.01, respectively). However, these differences were not statistically significant. A positive and significant correlation was found between AI and bcl-2I. CONCLUSIONS: Apoptosis was always present in the epithelium of the lesions and was more frequent in lesions with atrophic (quiescent) epithelium.