Dedifferentiation of odontogenic keratocyst epithelium after cyst decompression.

PURPOSE: Cytokeratin-10 expression by cystic epithelium has been shown in the suprabasilar layers of odontogenic keratocyts (OKCs) but not in dentigerous cysts. Cyst decompression and irrigation result in the loss of keratinization. In this study, we used cytokeratin-10 antibody staining to evaluate changes in OKC epithelium to determine if decompression/irrigation treatment results in an epithelial modulation that may be associated with lower long-term recurrence. METHODS: Fourteen OKCs were exteriorized by removal of mucosa and bone. An irrigation port was placed into the cyst for twice-daily irrigations. At 3-month intervals, panoramic radiographs were obtained and cyst-lining cells were sampled and stained for cytokeratin-10. Residual cystectomy was performed when necessary based on clinical and radiographic criteria, and the lining was evaluated by histologic and immunohistochemical examination. RESULTS: There were 6 males and 8 females with a mean age of 32 years. Ten cysts were mandibular, and 4 were maxillary. Average duration of irrigation was 8.4 months (range, 6 to 12 months), and the mean shrinkage of the radiolucency was 65% (range, 5% to 91%). All cytologic samples obtained at 3 and 6 months contained cytokeratin-10-positive epithelial cells. At the time of cystectomy, 9 of 14 cases were cytokeratin-10 negative and no longer showed histologic features of OKCs. Specimens from the remaining 5 patients were histologically consistent with OKC and were cytokeratin-10 positive. Mean treatment time of the cytokeratin-10-positive group was 7 months, and that of the cytokeratin-10-negative group was 9 months. CONCLUSION: Epithelial dedifferentiation and loss of cytokeratin-10 production were observed in 64% of patients treated by cyst decompression/irrigation after a 9-month average treatment time. Longitudinal follow-up of these patients will determine whether this change is associated with lower rates of recurrence than alternative OKC therapy.     

The odontogenic keratocyst: a cyst, or a cystic neoplasm?

The odontogenic keratocyst (OKC, currently designated by the World Health Organization as a keratocystic odontogenic tumor) is a locally aggressive, cystic jaw lesion with a putative high growth potential and a propensity for recurrence. Although it is generally agreed that some features of OKCs are those of a neoplasia, notably the relatively high proliferative rate of epithelial cells, controversies over the behavior and management of OKCs still exist. This article is intended to review this intriguing entity and to summarize the findings of recent studies related to the nature of OKCs and their clinical and therapeutic implications. Recent advances in genetic and molecular research, i.e., PTCH1 mutations and involvement of the Hedgehog signaling pathway, have led to increased knowledge of OKC pathogenesis which hints at potential new treatment options, although the question of whether the OKC is a cyst or a cystic neoplasm is yet to be answered with certainty. Since some advocate a more conservative treatment for OKCs, notably marsupialization and decompression, future treatment strategies may focus on molecular approaches and eventually reduce or eliminate the need for aggressive surgeries.     

Expression of keratinocyte growth factor and its receptor in odontogenic keratocysts

Background:  The mitotic activity of the epithelial cells of odontogenic keratocysts (OKCs) is greater than that of other odontogenic jaw cysts, and the mitotic activity of the epithelial cells decreases after marsupialization. Keratinocyte growth factor (KGF) interacts with its specific receptor (KGFR), and elicits the proliferation and/or differentiation of the various types of epithelial cells. The aim of this study was to investigate the expression of KGF/KGFR in OKCs before and after marsupialization.
Methods:  The expression of KGF was immunohistochemically detected in the specimens of 16 OKCs and 11 dentigerous cysts before and after marsupialization. The expression of KGF mRNA was measured in the fibroblasts isolated from OKCs by real-time PCR.
Results:  KGF was expressed in the epithelial cells and fibroblasts of 12 and seven of 16 OKC specimens, respectively. The intensity of the KGF expression in both the epithelial cells and the fibroblasts significantly decreased after marsupialization. KGFR was expressed throughout the epithelium in 15 of 16 OKC specimens, but the intensity of the KGFR expression did not change after marsupialization. The expression of KGF was detected in the epithelium of two of 11 dentigerous cyst specimens, but not in the fibroblasts before marsupialization. Real-time PCR revealed that recombinant human interleukin (IL)-1α increased the expression of KGF mRNA in the fibroblasts isolated from OKCs.
Conclusion:  KGF/KGFR signaling may play a crucial role in the epithelial cells of OKCs. Furthermore, the expression of KGF in the fibroblasts of OKCs is regulated by IL-1α.     

Molecular alterations in odontogenic keratocysts as potential therapeutic targets

The odontogenic keratocyst (OKC) is a cystic lesion, lined by uniformly thickened parakeratinized epithelium. Some lesions are large and tend to recur after surgical treatment. The neoplastic nature of OKCs remains a matter of dispute. It is known that some sporadic OKCs harbor PTCH1 mutations, and via the dissection of cyst epithelium, these mutations were demonstrated to occur much more frequently than previously thought. In addition to the classical PTCH1 mutations, Hedgehog pathway disturbance and Bcl‐2 protein overexpression, as detected via genome‐wide expression analysis of OKCs, have been published. Changes in DNA methylation patterns and alterations in microRNA expression levels have recently been reported in these lesions. We reviewed the molecular mechanisms that underlie the pathogenesis of OKCs as described over the past few years and explored the molecular alterations that can be therapeutically targeted.     

The multifocal nature of odontogenic keratocysts

The odontogenic keratocyst, OKC, is a very aggressive intraosseos lesion with a recurrence rate of approximately 25 percent to 60 percent.' The tendency for this lesion to "return" after surgical treatment has prompted studies to obtain more information concerning the inherent nature of the lesion. The OKC lesions are usually treated with enucleation of the soft tissue lining, curettage and ostectomy of the bony margins, or with more aggressive block resection. The purpose of this study was to characterize the multifocal aspect of the OKC and to demonstrate the presence of cystic lesions remote from the margins of the primarily diagnosed cyst itself. A retrospective chart review was conducted of seven patients who had sustained a long history of recurrent OKCs. Three types of documentation were reviewed for each patient: Orthopantomograms, cephalograms, and CT scans, which had been taken over the long-term course of the disease, Detailed operation reports of surgical procedures to treat the OKC lesions, and; Large histologic specimens from the six patients who received total resection of the involved mandibular bodies. These hemimandibulectomy slides offered a unique opportunity to observe OKC activity throughout a wide osseous area. All patients hod been operated multiple times over a period of 10 to 21 years, coming eventually to mandibular resection. The operating surgeon in all of the cases was one of the authors, Philip J. Boyne, DMD, MS, DSc. All patients exhibited the multifocal nature of OKCs with demonstrable cyst formation at distant sites in the mandible. Two patients had local recurrences at the margins of the primary lesion in addition to cyst formation at distant sites. The authors concluded that clinicians should respect the multifocal nature of OKCs. The "recurrences" observed in OKCs may not necessarily be due to the degree of skill of the surgeon or the technique used to eradicate the primary cyst, but instead are probably a reflection of the multifocal nature of the pathologic lesion itself. The OKC is a very aggressive intraosseos lesion of the jaws, which not infrequently clinicians detect in the process of routine oral examination.     

Immunohistochemical analysis of cell-cycle- and apoptosis-related factors in lining epithelium of odontogenic keratocysts

We examined the immunohistochemical expressions of cell-cycle- and apoptosis-related factors to investigate the possible role of these factors in odontogenic keratocyst (OKC). Expression of cyclin D1 and p16 protein was detected in the basal and parabasal cells in lining epithelium of OKCs and was found more frequently in basal cell nevus syndrome (BCNS)-associated OKCs than in primary or recurrent OKCs. Positivity for p21 protein was detected in basal to superficial cells, whereas that for p27 protein was detected in parabasal to superficial cells in lining epithelium of OKCs. DNA topoisomerase IIalpha reacted with nuclei in basal and parabasal cells of the lining epithelium of OKCs, and positive cells were observed in BCNS-associated OKCs significantly more frequently than in primary or recurrent OKCs. Expression of Fas in suprabasal to superficial cells and expression of Fas-L in basal and parabasal cells were detected in lining epithelium of OKCs. Immunoreactivity for caspase-3 was detected in basal to suprabasal or superficial cells in lining epithelium of OKCs. Single stranded (ss)DNA-positive nuclei were detected in superficial cells in lining epithelium of OKCs. Fas was more broadly distributed in BCNS-associated OKCs than in primary OKCs, and ssDNA-positive cells were observed in BCNS-associated OKCs significantly more frequently than in primary or recurrent OKCs. These results suggest that BCNS-associated OKCs might be a distinguishable entity from solitary OKCs.     

正角化牙源性囊肿的临床病理及免疫组化研究

目的：探讨一组正角化牙源性囊肿（orthokeratinized odontogenic cyst,OOC)的临床病理及免疫组化特点。方法：以OOC的名称报告20例，观察其组织学和免疫组化特点，并与牙源性角化囊肿（odontogenic keratocyst,OKC)病变进行比较。结果：本组病例约占同期所有OKC的9．9％（20／202），其中男性14例，女性6例，就诊平均年龄39．1％；随访资料显示：15例患者行囊肿刮治后无复发；组织学和免疫组化比较发现：OOC和OKC之间差异有显著性，OOC上皮不表现OKC上皮的形态分化特点，细胞增殖活性较低。结论：OOC可能代表一组有别于牙源性角化囊肿的颌骨病损。     

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.     

Evaluation of collagen in connective tissue walls of odontogenic cysts –A histochemical study

J Oral Pathol Med (2011) 40 : 257–262 Background: The purpose of this study was to evaluate the nature of collagen in the connective tissue walls of odontogenic cysts, like the odontogenic keratocyst (OKC), dentigerous cyst and radicular cyst using picrosirius red stained sections. Furthermore, it was intended to assess if the capsular connective tissue can affect the nature of overlying epithelium, thus emphasizing the role of epithelial–mesenchymal interactions in biological behaviour of the cysts. Materials and method: The material for the study included 51 formalin‐fixed paraffin‐embedded tissue blocks (15 odontogenic keratocyst, 15 dentigerous cysts, 15 radicular cysts and four normal mucosa and two dental follicular tissue as controls), retrieved from the Department of Oral Pathology and Microbiology, MCODS, Manipal. Tissue blocks were sectioned at 5‐μm thickness, stained with picrosirius red stain and observed with polarization and light microscopy. Results: Few sections of OKC and dentigerous cyst exhibited greenish‐yellow birefringence in sub‐epithelial region, whereas others showed a yellowish‐orange birefringence under polarization microscopy. Most radicular cysts had yellowish‐orange to orange birefringence. Shift in colour in case OKC and dentigerous cyst was attributed to the presence of inflammation in those sections. These regions also exhibited either a change in phenotype or thickness of overlying epithelium. Conclusion: This technique can be used to study the nature of collagen fibres in odontogenic cyst walls. Further studies with an increased sample size and using various epithelial and mesenchymal markers and ssDNA antibodies should be carried out to confirm the effect of epithelial–mesenchymal interactions on the nature of epithelium of odontogenic cysts.     

Immunohistochemical study of the orthokeratinized odontogenic cyst: a comparison with the odontogenic keratocyst

OBJECTIVE: Orthokeratinized odontogenic cyst (OOC) is a developmental cyst that occurs in the maxilla and the mandible and is defined by the World Health Organization as the uncommon orthokeratinized type of odontogenic keratocyst (OKC). However, studies have shown that OOC has peculiar clinicopathologic aspects and biologic behavior when compared with other developmental odontogenic cysts, especially OKCs. Therefore, in this study, the immunohistochemical profile of the OOC was delineated and compared with that of the OKC. STUDY DESIGN: Twelve cases of OOC were submitted to a panel of antibodies composed of cytokeratins (10, 13, and 14) and extracellular matrix proteins: fibronectin, types I and III collagen, and tenascin. For comparative means, 12 cases of OKC also were submitted to the same panel of antibodies. RESULTS: The results obtained showed that OOCs expressed cytokeratin 10 and showed variable expression of cytokeratins 13 and 14. Fibronectin and collagen types I and III also were expressed in OOC in a fibrillar aspect. OKC showed only the superficial keratin layer positive to cytokeratin 10 and the basal and suprabasal layers with variable expression of cytokeratin 14, and cytokeratin 13 was present in the upper epithelial layers. The extracellular matrix proteins showed a nonfibrillar expression. Tenascin was immunoexpressed only in OKC. CONCLUSION: The immunohistochemical profile of the studied cysts clearly showed that OOC presents a well-formed cystic enveloping, whereas the OKC profile is compatible with a more aggressive biologic behavior.     

Marsupialization is the optimal treatment for odontogenic keratocyst in pediatric patients

Odontogenic keratocyst (OKC) shows a high rate of recurrence, so aggressive treatment has been recommended. However, if the patient is a child and still has unerupted permanent teeth in the region of the OKC, aggressive treatment may not be the best option. We report herein a case of multiple OKCs in a pediatric patient treated using marsupialization five times and enucleation twice. Recurrence was not observed after surgical treatments in 7 years of follow-up. We suggest that treatment with marsupialization should be considered as the first-line treatment strategy for young patients with OKC.     

The immunoprofile of odontogenic keratocyst (keratocystic odontogenic tumor) that includes expression of PTCH, SMO, GLI-1 and bcl-2 is similar to ameloblastoma but different from odontogenic cysts

Background:  The aggressive biological behavior of odontogenic keratocysts (OKCs), unlike that of other odontogenic cysts, has argued for its recent re-classification as a neoplasm, 'keratocystic odontogenic tumor'. Identification of mutations in the PTCH gene in some of the OKCs that were expected to produce truncated proteins, resulting in loss of control of the cell cycle, provided additional support for OKCs having a neoplastic nature.
Methods:  We investigated the immunohistochemical expression of the sonic hedgehog (SHH) signaling pathway-related proteins, PTCH, smoothened (SMO) and GLI-1, and of the SHH–induced bcl-2 oncoprotein in a series of primary OKC (pOKC), recurrent OKC (rOKC) and nevoid basal cell carcinoma syndrome-associated OKCs (NBCCS-OKCs), and compared them to solid ameloblastomas (SAMs), unicystic ameloblastomas (UAMs), 'orthokeratinized' OKCs (oOKCs), dentigerous cysts (DCs) and radicular cysts (RCs).
Results:  All studied lesions expressed the SHH pathway-related proteins in a similar pattern. The expression of bcl-2 in OKCs (pOKCs and NBCCS-OKCs) and SAMs was significantly higher than in oOKCs, DCs and RCs ( P  <   0.001).
Conclusions:  The present results of the immunoprofile of OKCs (that includes the expression of the SHH-related proteins and the SHH-induced bcl-2 oncoprotein) further support the notion of OKC having a neoplastic nature. As OKCs vary considerably in their biologic behavior, it is suggested that the quality and quantity of interactions between the SHH and other cell cycle regulatory pathways are likely to work synergistically to define the individual phenotype and corresponding biological behavior of this lesion.     

下颌骨大型囊性病变开窗术后骨腔改变及其影响因素

目的:观察牙源性角化囊肿(odontogenic keratocyst,OKC),单囊型成釉细胞瘤(unicystic ameloblastoma,UAB)和根尖囊肿(radicular cyst,RC)开窗减压术后骨腔的改变,并分析其影响因素。方法:27例颌骨囊性病变患者中,OKC 16例,RC 6例,UAB 5例,均行开窗减压术,术后规律随访。运用Image J软件测量术前、术后口腔曲面体层片上病变区域骨密度和囊腔大小的变化,并进行分析。结果:OKC、UAB和RC开窗减压术后,骨腔逐渐缩小,骨密度逐渐增大。术后3个月,不同病理类型颌骨囊性病变开窗减压术后愈合速度不同,差异有统计学意义(P<0.05);术后6个月,3种类型囊性病变骨密度增加速度的差异无统计学意义(P>0.05)。骨腔大小变化与初始囊腔大小有一定的相关性(P<0.05)。骨密度变化与初始囊腔大小相关(P<0.05),不同病理类型囊性病变的骨密度增加速度不同,差异有统计学意义(P<0.05)。年龄与骨腔大小变化无相关性(P>0.05)。结论:开窗减压术治疗颌骨囊性病变效果显著,初始囊腔大小及病理类型对OKC、UAB和RC的愈合有一定的影响,年龄不影响开窗减压术后成骨速度。     

Survivin、bcl-2、caspase-3在牙源性角化囊肿中的表达及意义

目的检测凋亡相关蛋白survivin、bcl-2、caspase-3在角化囊肿中的表达,探讨其在角化囊肿发生发展中的意义。方法免疫组织化学方法检测20例角化囊肿(10例原发和10例复发)、10例含牙囊肿和10例根端囊肿中survivin、bcl-2、cas-pase-3的表达。结果Survivin、bcl-2、caspase-3阳性染色分别见于13(65%)、13(65%)、9(45%)例角化囊肿。Survivin、bcl-2在角化囊肿上皮基底层细胞中阳性表达,阳性率显著高于含牙囊肿和根端囊肿;caspase-3在角化囊肿上皮表层细胞表达。Survivin的表达与bcl-2正相关,与caspase-3无明显相关性。结论Survivin、bcl-2、caspase-3在角化囊肿形成和发展中起一定作用。     

Odontogenic keratocyst: Review of 256 cases for recurrence and clinicopathologic parameters

Odontogenic keratocyst (OKC) is of particular interest because of its high recurrence rate and aggressive behavior. Two hundred fifty-six cases of OKC were reviewed for the age of the patient at diagnosis, sex of the patient, OKC location, and radiographic findings, and 132 patients with OKC were observed to estimate recurrence, which was analyzed for age, sex, location, and several histopathologic findings. OKCs occurred more frequently in men (58.6%) than in women (41.4%), and they occurred in patients within a wide age range, most commonly in patients in the third decade of life (28.9%), followed by those in the second decade (25.0%); the mean age of patients with OKC was 30.8 years. One hundred ninety-six of the 256 cases (76.5%) occurred in the mandible, and the other 60 cases (23.5%) occurred in the maxilla. The mandibular molar and the premolar areas (51.2%) were the most common sites, and the most frequent clinical manifestations at first admission were swelling, pain, or both (82.4% of total cases). Radiographic impressions included dentigerous cyst (27.3%), OKC (25.4%), primordial cyst (14.8%), ameloblastoma (11.7%), residual cyst (9.8%), and radicular cyst (3.1%). The frequency of recurrence at the follow-up examination was 58.3%. There was no significant difference in the recurrence rate on the basis of the sex of the patient. However, OKCs had a significantly higher recurrence rate in patients in the fifth decade of life than in patients in the other age groups (P = .005).Recurrence rates were significantly dependent on the sites of involvement, and OKCs in the mandibular molar region had significantly higher recurrence rates than those in other sites (P = .001). The histopathologic presence of one or more daughter cysts was significantly related to recurrence (P = .03).     

A radiologic analysis of dentigerous cysts and odontogenic keratocysts associated with a mandibular third molar

OBJECTIVE: The purpose of this study was to discriminate radiographically between dentigerous cysts (DCs) and odontogenic keratocysts (OKCs) associated with a mandibular third molar. STUDY DESIGN: The material consisted of panoramic radiographs of dentigerous cysts (44 patients, 45 cysts) and odontogenic keratocysts (15 patients, 16 cysts), all of which were related to a mandibular third molar. The radiographic images were analyzed with reference to the patients' ages and symptoms. RESULTS: The mean age of patients in the OKC group was less than that of patients in the DC group. The mean area of the cysts in the OKC group was larger than that of those in the DC group. The mean distance from the second to the third molar in the DC group was greater than that in the OKC group. Although there was a significant correlation between the area and distance in the DC and OKC groups, the patients' ages did not significantly correlate to the area and distance of either cyst. CONCLUSIONS: The OKCs had a tendency toward rapid growth in the patient's youth but short movement of a third molar compared with the DCs. The DCs and OKCs do not appear to develop gradually from the period when follicles or dental lamina were formed but arise at various periods randomly.     

Odontogenic Keratocyst Is Frequently Misdiagnosed for a Lateral Periodontal Cyst in Premolar and Anterior Tooth-Bearing Areas

IntroductionRadiolucent lesions with gingival swelling found in the premolar and intercanine region can elicit a different clinical diagnosis than one confirmed by histologic findings. The purpose of the study is to identify and present the frequency of the unexpected microscopic diagnosis of odontogenic keratocyst (OKC) in a location preoperatively favoring a lateral periodontal cyst (LPC) with similar clinical and radiographic appearance.MethodsA retrospective analysis of biopsies received from 2011 and 2019 was performed, and the number of LPC and OKC cases was assessed. The alignment of clinical and radiographic diagnosis to histologic findings and anatomic location was analyzed, and the number of OKC cases preoperatively misdiagnosed as LPCs was identified.ResultsA total of 79,257 biopsies were received. Of those, 184 were diagnosed as LPCs and 742 as OKCs. For all preoperatively diagnosed LPCs, the clinical and histologic diagnosis aligned; however, 182 of 742 OKCs were submitted with a clinical misdiagnosis of LPCs. The location of these lesions with the unanticipated diagnosis overlapped with those for LPCs, specifically the maxillary and mandibular anterior and premolar regions.ConclusionsRadiolucent lesions with gingival swelling in the premolar and intercanine region are frequently clinically and radiographically misdiagnosed. A biopsy should be considered in all cases to establish the correct pathologic diagnosis and treatment course.     

Odontogenic Keratocyst: To Decompress or Not to Decompress? A Comparative Study of Decompression and Enucleation Versus Resection/Peripheral Ostectomy

PURPOSE: We discuss the outcome of 2 well-established and widely accepted methods used for the treatment of odontogenic keratocyst (OKC), enucleation with peripheral ostectomy or resection and decompression followed by enucleation and peripheral ostectomy. PATIENTS AND METHODS: A retrospective chart review of all cases of OKC treated in the University of Maryland's Department of Oral and Maxillofacial Surgery between 1994 and 2004 was undertaken. A total of 31 patients with OKCs was identified. Three of these patients diagnosed with basal cell nevus syndrome and multiple OKCs and 6 patients who did not have adequate follow-up were excluded from this study; thus, 22 patients were evaluated. Of these 22 patients, 11 were treated with resection or enucleation with peripheral ostectomy (group I) and 11 were treated with decompression followed by enucleation when indicated (group II). RESULTS: A total of 22 patients with biopsy-proven OKC ranging in age from 18 to 90 years were separated into 2 treatment arms. Group I comprised 6 females and 5 males, age 18 to 71 years, with 6 OKCs located in the mandible and 5 in the maxilla. Group II comprised 6 females and 5 males, age 24 to 90 years, with 10 OKCs in the mandible and 1 in the maxilla. The choice of treatment approach was based on the size of the cyst, recurrence status, and radiographic evidence of cortical perforation. The last follow-up revealed no recurrences in group I and 2 recurrences in group II. Both patients with recurrence in group II had undergone enucleation of the same lesion in the past, and both cysts recurred within 2 years after initial treatment. CONCLUSIONS: Our study results concur with the literature regarding recurrence rates of OKC. The aggressive nature of some OKCs necessitates equally aggressive treatment, whereas long-term follow up even for nonsyndromic patients with single lesions is of paramount importance. Age of the patient and the site and histological characteristics of the treated lesions were not significantly associated with the incidence of recurrence.     

P53 protein expression in odontogenic cysts

p53 protein seems to be related to the suppression of cell proliferation. p53-positive tissues seem to have a higher proliferative activity than p53-negative ones. Odontogenic keratocyst (OKC) has a different behavior from other types of cysts because it is more aggressive, with a tendency to recurrence. Twenty-two dentigerous cysts, 24 radicular cysts, and 20 OKCs were used in the present study. Two dentigerous cysts (9.1%), 2 radicular cysts (8.3%), and 9 OKCs (45%) expressed the p53 protein. The differences between the three groups were statistically significant (p = 0.003). In 10 cases of OKCs epithelial dysplasia was found. One of the 10 OKCs without dysplasia and 8 of the 10 OKCs with dysplasia were p53-positive: the difference between the two groups was statistically significant (p = 0.007). The overexpression of p53 protein was not on the other hand correlated with the occurrence of multiple, bilateral, and recurrent OKCs. Moreover the distribution of p53-positive cells was parabasal in contrast with other types of cysts. These qualitative and quantitative differences in proliferative activity in OKCs seem to point to an alteration in cell cycle control.