Open Access

Histopathological and immunohistochemical study in keratocystic odontogenic tumors: Predictive factors of recurrence

  • Authors:
    • Tomofumi Naruse
    • Kentaro Yamashita
    • Souichi Yanamoto
    • Satoshi Rokutanda
    • Yuki Matsushita
    • Yuki Sakamoto
    • Hiroshi Sakamoto
    • Hisazumi Ikeda
    • Tohru Ikeda
    • Izumi Asahina
    • Masahiro Umeda
  • View Affiliations

  • Published online on: March 24, 2017     https://doi.org/10.3892/ol.2017.5905
  • Pages: 3487-3493
  • Copyright: © Naruse et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to identify the most useful markers for predicting recurrence of keratocystic odontogenic tumors (KCOTs). A total of 65 tumor samples from 63 patients diagnosed with typical parakeratinized cysts and KCOTs between 1992 and 2014 were retrospectively studied. Clinical and histopathological data and treatment modality were reviewed. In addition, the expression profiles of Ki‑67, cluster of differentiation (CD)34 and podoplanin were assessed using immunohistochemistry. The association between these factors and the rate of KCOT recurrence was evaluated. The presence of daughter cysts, epithelial islands and high Ki‑67, CD34 and podoplanin expression levels were revealed to be associated with tumor recurrence. In particular, univariate analysis revealed that high CD34 expression levels were significantly associated with tumor recurrence (P=0.034), as was conservative surgical treatment (P=0.003). Multivariate analysis revealed that conservative treatment was the greatest independent risk factor for tumor recurrence (odds ratio=13.337; P=0.018). These results suggest that overexpression of CD34 may be a potent predictor of tumor recurrence and radical treatment of the teeth that are in contact with the tumors is recommended in order to prevent tumor recurrence.

Introduction

Keratocystic odontogenic tumors (KCOTs) are classified as benign odontogenic tumors by the World Health Organization (WHO) (1). A KCOT is defined as a benign unicystic or multicystic intraosseous tumor of odontogenic origin, with a characteristic lining of parakeratinized stratified squamous epithelium that is noted for its locally aggressive nature and capacity for recurrence (1,2). The high rate of recurrence is due to the neoplastic nature of these tumors, including a high rate of proliferative activity and angiogenesis, and the presence of daughter cysts and epithelial islands (35). The incomplete surgical removal of the epithelial components of KCOTs due to their fragility is also a factor contributing to recurrence (3,6).

Various markers of proliferation as well as microvessel density (MVD) have previously been examined with regard to their capacity to predict tumor recurrence in immunohistochemical studies (38). One such marker of proliferation is Ki-67, a prototypical cell cycle-associated nuclear protein that is expressed by proliferating cells in all phases of the cell cycle, with the exception of G0, and is rapidly degraded following mitosis, with a half-life of ≤1 h (7,8). The immunohistochemical detection of Ki-67 has been used to evaluate the proliferative potential of tumor cells, and to predict the recurrence of KCOTs (7,8).

MVD is determined by detecting the expression levels of cluster of differentiation (CD)34, and is frequently used to quantify angiogenesis in benign and malignant oral tumors, including KCOTs (4,9,10). In our previous study, it was reported that CD34 expression was associated with tumor growth in oral squamous cell carcinoma (10).

Podoplanin is a transmembrane glycoprotein that is specifically expressed by lymphatic endothelial cells, and its expression is associated with lymph node metastasis in head and neck squamous cell carcinoma (11). Podoplanin has also been detected in a variety of neoplastic tissues, and its expression may be associated with the extracellular matrix signaling pathways, neoplastic nature and proliferative capacity of KCOTs (5,12,13).

Although these markers are useful for predicting tumor recurrence, to the best of our knowledge, no previous studies have examined their utility in the context of surgical treatment procedures for KCOTs. In the present study, clinicopathological and immunohistochemical analyses were combined in order to investigate how these factors may be associated with KCOT recurrence.

Materials and methods

Patients

The present study was approved by the independent ethics committee of Nagasaki University Hospital (Nagasaki, Japan; approval no. 15061127). The medical records of patients who were diagnosed with a typical parakeratinized cyst and KCOT between 1992 and 2014 at Nagasaki University Hospital according to the WHO classification, and who underwent a complete surgical tumor excision, were retrospectively reviewed in the current study. Paraffin embedded samples from these patients were obtained from the pathology department of Nagasaki University Hospital. Information regarding patient gender and age, the site and duration of the lesion prior to treatment, surgical modality and the time to follow-up and tumor recurrence was obtained from the patient records. Patients for whom the follow-up period was <6 months, and those who were diagnosed with nevoid basal cell carcinoma syndrome (NBCCS), were omitted from the current study. One patient with multiple lesions was selected for the present study as they had not satisfied the diagnostic criteria for NBCCS (14).

Immunohistochemistry

Paraffin-embedded sections of resected KCOT tissue specimens cut at 4 µm were deparaffinized in xylene and were soaked in 10 mmol/l citrate buffer (pH 6.0) and placed in an autoclave at 121°C for 5 min for antigen retrieval. Endogenous peroxidase was blocked by incubation with 0.3% H2O2 in methanol for 30 min. Immunohistochemical staining was performed using the Envision system (ENVISION+; Dako; Agilent Technologies, Inc., Glostrup, Denmark). The following antibodies were used as primary antibodies: Monoclonal antibody for Ki-67 (dilution, 1:50; cat. no., M7240; Dako, Agilent Technologies, Inc.), CD34 (undiluted; cat. no., M716529; Dako, Agilent Technologies, Inc.) and podoplanin (dilution, 1:50; cat. no., M3619; Dako, Agilent Technologies, Inc.) derived from mouse. The sections were then washed in Dulbecco's PBS, followed by incubation with the primary antibodies at 4°C overnight. Following the incubation of sections with secondary antibodies (undiluted; cat. no., K4001; Dako, Agilent Technologies, Inc.) for 30 min at room temperature, the reaction products were visualized by immersing the sections in diaminobenzidine solution, and the samples were counterstained with Meyer's hematoxylin and mounted. Negative controls were created by the replacement of the primary antibody with phosphate-buffered saline (PBS). Ki-67 expressions were evaluated by light microscopy in the basal to suprabasal cell layers by calculating the mean number of positive cells in 5 randomly selected visual fields of each tissue section. The MVD was determined from CD34 expression levels in the stromal cells bordering the tumor parenchyma, by evaluating the number of CD34-positive capillaries in the 200-µm region immediately below the epithelium, as previously described (4). The neoplastic character of the tumor tissues was assessed using podoplanin labeling in the basal to suprabasal cell layers by calculating the total immunoreactivity score as the product of proportional scores, which were based on the estimated fraction of positively labeled tumor cells for all tumor cells (0, none; 1, <25%; 2, 25–50%; 3, >50%) (5). All immunohistochemical assessments were performed blind by two examiners, and based on the results of these assessments, the present study compared the responses and characterized the tumors.

Statistical analysis

The associations between marker expression levels and the patient clinicopathological features were analyzed using Fisher's exact test. Continuous data are presented as the median with interquartile range (IQR). Multiple logistic regression analysis and univariate and multivariate logistic regression analyses were performed in order to identify independent factors for predicting tumor recurrence. Predictors that were not determined to be associated with recurrence by the univariate analysis were not included in the multivariate analysis. P<0.05 was considered to indicate a statistically significant result.

Results

Clinical characteristics of patients with KCOTs

Medical records were reviewed for a total of 65 tumors in 63 patients who were treated during the aforementioned 22-year period, and the clinicopathological features are summarized in Table I. Males and females accounted for 58.7 and 41.3% of patients, respectively. The median age of the patients was 41 years (range, 10–87 years). Regarding the site of tumor involvement, 44 patients (69.8%) had mandibular tumors, 18 (28.6%) had maxillary tumors, and 1 (1.6%) had tumors involving the maxilla and the mandible. Radiographic examination using panoramic and computed tomography revealed unilocular radiolucency in 53 tumors (81.5%), with the remainder (18.5%) being multilocular. The median tumor size was 35 mm (range, 5–120 mm). Single tumors were detected in 62 patients (98.4%), whereas 1 patient (1.6%) had three tumors. Recurrence was observed for 13/65 tumors (20.0%) and the median time to recurrence was 36 months (range, 10–137 months). Of the 65 tumors, 55 (84.6%) were treated with surgical enucleation, and 10 (15.4%) with marsupialization and subsequent enucleation. The median follow-up period for marsupialization was 5.5 months (range, 5–14 months). In 24 tumors (36.9%), enucleation was used in combination with peripheral ostectomy with a bone bur (Table II). The most frequently used treatment modality for cases in which the roots of teeth were in contact with the margins of the primary tumor was conservative (no extraction; 37 cases; 56.9%), which included 29 cases of no treatment and 8 cases of apicoectomy; radical treatment (extraction) was administered for 28 tumors (43.1%), including 22 extractions and 6 cases in which there was no contact with the root (solitary tumor; Table III). No patients underwent a partial mandibulectomy or maxillectomy.

Table I.

Clinicopathological characteristics of 65 keratocystic odontogenic tumors in 63 patients.

Table I.

Clinicopathological characteristics of 65 keratocystic odontogenic tumors in 63 patients.

CharacteristicValue
Gender, n (%)
  Male37 (58.7)
  Female26 (41.3)
Age, years
  Range10–87
  Median41
Site of involvement, n (%)
  Maxilla18 (28.6)
  Mandible44 (69.8)
  Mixed1 (1.6)
Number of tumors, n (%)
  Single62 (98.4)
  Multiple1 (1.6)
X-ray results, n (%)
  Unilocular53 (81.5)
  Mutilocular12 (15.5)
Tumor size, mm
  Range5–120
  Median35
Follow-up period, months
  Range6–252
  Median16
Daughter cysts/epithelial islands, n (%)
  Absent33 (50.7)
  Present32 (49.3)
Recurrence, n (%)
  No52 (80.0)
  Yes13 (20.0)
Recurrence period, months
  Range10–137
  Median36

Table II.

Surgical modality used in the treatment of keratocystic odontogenic tumors (n=65).

Table II.

Surgical modality used in the treatment of keratocystic odontogenic tumors (n=65).

FactorValue
Marsupialization and subsequent enucleation, n (%)10 (15.4)
Follow-up period of marsupialization, months
  Range5–14
  Median5.5
Enucleation alone, n (%)55 (84.6)
Peripheral ostectomy, n (%)
  Absent41 (63.1)
  Present24 (36.9)

Table III.

Surgical modality used when the root of the tooth was in contact with the margin of the primary keratocystic odontogenic tumor (n=65).

Table III.

Surgical modality used when the root of the tooth was in contact with the margin of the primary keratocystic odontogenic tumor (n=65).

Surgical modalityNo. of cases (%)
Conservative treatment (non-extracted)37 (56.9)
  No treatment29 (44.6)
  Apicoectomy8 (12.3)
Radical treatment (extracted)28 (43.1)
  No contact with primary tumors6 (9.3)
  Extraction22 (33.8)
Histopathological and immunohistochemical analysis

The presence of one or more daughter cyst (Fig. 1A) or epithelial island (Fig. 1B) in the cyst wall was observed in 32/65 tumors (49.3%), of which 7 recurred during the follow-up period. No daughter cysts or epithelial islands were observed in the cyst wall of 33 tumors (50.7%), and 6 of these cases demonstrated recurrence during the follow-up period.

Hematoxylin-eosin staining (Fig. 2A) and immunohistochemical analysis (Fig. 2B-D) revealed the presence of Ki-67-positive cells in the basal and suprabasal cell layers of the tissue samples. The median Ki-67 labeling indexes (LI) was 7.5% (IQR=1.8–17.26) in all tumors, and 5.0% (IQR=0–17.3) and 12.5% (IQR=7.5–17.1) in non-recurrent and recurrent tumors, respectively. There were 4 tumors (13.8%) with an LI ≤7.5% and 9 (39.1%) with an LI >7.5% that demonstrated recurrence (Fig. 2B). CD34-positive blood vessels were observed in the connective tissues and the MVD was 6.5% (IQR=3–10) in all tumors, and 5.0% (IQR=3–9.25) and 8.5% (IQR=6.25–14.5) in non-recurrent and recurrent tumors, respectively. There were 3 tumors with an MVD <6.5 and 10 with an MVD >6.5 that demonstrated recurrence (Fig. 2C; Table IV). Podoplanin was expressed in the cell membrane and cytoplasm of the majority of cells in the basal and suprabasal cell layers. Recurrence was observed in 3 tumors with scores of 0 or 1, and in 10 tumors with scores of 2 or 3 (Fig. 2D; Table V).

Table IV.

Ki-67 and CD34 immunoreactivity (MVD) in keratocystic odontogenic tumors.

Table IV.

Ki-67 and CD34 immunoreactivity (MVD) in keratocystic odontogenic tumors.

FactorNo. of casesKi-67 LI, % (IQR)MVD, % (IQR)
Non-recurrence525.0 (0–17.3)5.0 (3–9.25)
Recurrence1312.5 (7.5–17.1)8.5 (6.25–14.5)
Total657.5 (1.8–17.3)6.5 (310)

[i] Data are presented as the median with interquartile range. CD34, cluster of differentiation 34; MVD, microvessel density; LI, labeling index.

Table V.

Podoplanin immunoreactivity in keratocystic odontogenic tumors.

Table V.

Podoplanin immunoreactivity in keratocystic odontogenic tumors.

Number of patients

FactorTotalScore 0Score 1Score 2Score 3
Non-recurrence52681622
Recurrence130328

Uni- and multivariate analyses of tumor recurrence. A univariate analysis revealed that high CD34 expression levels and conservative treatment were significantly associated with tumor recurrence (P=0.034 and P=0.003, respectively). The presence of daughter cysts or epithelial islands and the expression of Ki-67 and podoplanin, were not associated with recurrence; however the rate of each was observed to increase in tumor tissue that were positive for these factors, as compared with tissues that were negative (Table VI). A multivariate analysis revealed that conservative treatment was the only independent predictor of tumor recurrence (odds ratio=13.337; P=0.018; Table VII).

Table VI.

Univariate analysis of keratocystic odontogenic tumor recurrence.

Table VI.

Univariate analysis of keratocystic odontogenic tumor recurrence.

Recurrence, n

Variable+Recurrence rate (%)P-value
Gender 0.127
  Male271027.0
  Female25  310.7
Age, years 0.764
  ≤4125  721.9
  >4127  618.2
Tumor size, mm 0.356
  ≤3529  517.2
  >3523  825.8
Tumor site 0.485
  Maxilla15  316.7
  Mandible371021.3
Radiographic findings 0.447
  Unilocular431018.9
  Multilocular  9  325.0
Daughter cyst + epithelial islands 0.764
  Absent27  618.1
  Present25  721.9
Ki-67, % 0.096
  ≤7.529  412.1
  >7.523  928.1
CD34, MVD 0.034
  ≤6.529  3   9.4
  >6.5231030.3
Podoplanin score 0.542
  0–114  317.6
  2–3381020.8
Surgical modality 0.317
  Marsupialization + enucleation  7  330.0
  Enucleation alone451018.1
Surgical modality 0.003
  Conservative251232.4
  Radical27  1   3.6
Peripheral osteotomy 0.431
  Absent32  921.9
  Present20  416.7

[i] Ki-67, marker of proliferation Ki67; CD34, cluster of differentiation 34; MVD, microvessel density.

Table VII.

Multivariate analysis of regional keratocystic odontogenic tumor recurrence.

Table VII.

Multivariate analysis of regional keratocystic odontogenic tumor recurrence.

ParameterOdds ratio95% CIP-value
CD34 (≤6.5 vs. >6.5)   4.3660.992–19.2060.051
Surgical modality (conservative vs. radical)13.337   1.565–113.6470.018

[i] CD34, cluster of differentiation 34; CI, confidence interval.

Discussion

Investigation of the pathological and neoplastic characteristics and the proliferative and angiogenic activities of KCOTs may provide a means of predicting tumor recurrence and reveal novel treatment approaches. Therefore, the present study aimed to identify the most useful markers associated with KCOT recurrence.

The association between the tumor histopathological features and KCOT recurrence was examined, and the presence of daughter cysts or epithelial islands showed a high recurrence rate compared with the absence of them, but the result was not significant. Previous studies have reported that the presence of daughter cysts is significantly associated with a high rate of tumor recurrence (6), as well as a high frequency of allelic loss in tumor suppressor genes, suggesting a neoplastic nature (15). However, another study refuted these results (8). The disparity may be due to the number of cases examined in each of these studies.

The median LI for Ki-67 for basal and suprabasal cell layers was previously demonstrated to be 4.5–13.8% in recurrent tumors, representing a significant association (4,7,8). Ki-67 is a marker that is often used to assess cell proliferation in aggressive tumors such as oral cancer or ameloblastoma (16,17). In the present study, the median LI for Ki-67 was ~12.5% in the recurrent group, as compared with ~5.0% in the non-recurrent group; however, univariate analysis determined that there was no significant difference between the two groups. The discrepancy between the previously reported values and the results of the present study may be due to variations in the evaluations. In the present study, the median positive cell rate was used as cut off value for univariate analysis, but different statistical analysis was used in other studies (4,7) or 10% for Ki-67 positive cells were used as cut off value for high expression (8).

Angiogenesis is essential for the proliferation of tumor cells (4) and is evaluated by MVD, of which has previously been implicated in oral squamous cell carcinoma (10). When nutrient consumption in the tumor parenchyma exceeds the local supply of nutrients, the tumor cells enter a hypoxic state and produce vascular endothelial growth factor to ensure the provision of the necessary nutrients and oxygen by promoting angiogenesis (10,18). Previous studies have reported that the typical diffusion range for nutrients and oxygen is 70–200 µm (4); therefore, the tumor cells that are located >100 µm from blood vessels often become hypoxic (19). From these studies, angiogenesis in the 200 µm region immediately below the epithelium was investigated in the present study, and it was identified that the number of blood vessels positive for CD34 expression was associated with the rate of tumor recurrence. Previous studies have reported that CD34 expression is a histopathological marker of tumor aggressiveness (4,9,20); however, to the best of our knowledge, the present study is the first to demonstrate that angiogenesis directly beneath the epithelium is a significant factor in predicting the recurrence of KCOTs.

The expression of podoplanin in KCOT tissues reflects the neoplastic activity of the tumor, including cell proliferation and local invasiveness (5,12,13,21). Podoplanin-positive cells are also involved in extracellular matrix remodeling, which is associated with cell growth (13,21). In the present study, ~91.8% of all tumors examined were positive for podoplanin expression; however, univariate analysis revealed that there was no significant difference in podoplanin expression levels between the recurrent and non-recurrent tumor tissues. Previous studies have indicated that podoplanin expression levels are also indicative of tumor aggressiveness (5,12,13,21), and that they are decreased following marsupialization or decompression (13). In the present study, no significant difference in the rate of recurrence was identified between those tumors treated with marsupialization and subsequent enucleation and those treated by enucleation alone, which may also suggest that podoplanin expression levels are not useful as a marker for KCOT recurrence.

Although there have been numerous retrospective studies that have investigated the association between the type of surgical procedure administered and the rate of tumor recurrence (6,2224), to the best of our knowledge, no previous studies specifically examined the correlation between tumor recurrence and the surgical modality used when the tooth root was in contact with the margins of the primary tumor. The results of the current study demonstrated that conservative treatment was significantly associated with tumor recurrence; therefore, teeth that remain in contact with primary tumors may present a risk for recurrence, as previously suggested (23). The majority of primary KCOTs occur in the mandibular molar region; an apicoectomy against mandibular molars is often inaccurate because it is anatomically difficult to access compared with anterior region (23). Although peripheral osteotomy with a bone bur has previously been used to prevent recurrence (23,24), it was identified in the present study that the use of peripheral osteotomy was not associated with the rate of tumor recurrence.

Multivariate analysis identified conservative treatment to be the only independent factor for predicting KCOT recurrence. Therefore, it was hypothesized that the surgical modality may be more useful for predicting KCOT recurrence, compared with histopathological factors or molecular markers. Although NBCCS was omitted and solitary KCOT cases were selected to reduce biases associated with tumor recurrence, residual confounding effects may remain due to the retrospective study design. Additionally, a potential limitation of the current study was the relatively small number of patient cases that were examined, due to the low incidence of KCOT amongst oral lesions. Therefore, further prospective and intergroup studies are required.

In conclusion, overexpression of CD34 may be a potent marker of tumor recurrence and the radical treatment (extraction) of teeth that are in contact with tumors is a promising approach for preventing the recurrence of KCOTs. However, as KCOT is more prevalent in younger patients, this may not be a widely acceptable treatment due to cosmetic and occlusional complications; therefore, a more elaborate peripheral osteotomy with a bone bur may be required when apicoectomy is selected.

Glossary

Abbreviations

Abbreviations:

KCOT

keratocystic odontogenic tumor

CD

cluster of differentiation

MVD

microvesssel density

NBCCS

nevoid basal cell carcinoma syndrome

WHO

World Health Organization

LI

labeling index

References

1 

Barnes L, Eveson JW, Reichart P and Sidransky D: Pathology and genetics of head and neck tumours. WHO Classif Tumour. 9:2912005.

2 

Neville BW, Damm DD, Allen CM and Bouquot JE: Oral and Maxillofacial Pathology. 3rd (eds). Saunders/Elsevier. St. Louis, MO: 683–687. 2009.

3 

Mendes RA, Carvalho JFC and van der Waal I: Characterization and management of the keratocystic odontogenic tumor in relation to its histopathological and biological features. Oral Oncol. 46:219–225. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Suemitsu M: A pathomorphological study of fractal analysis in parenchymal-stromal border on keratocystic odontogenic tumor-with special reference to proliferative activity and vascular distribution. Int J Oral-Medical Sci. 10:372–383. 2012. View Article : Google Scholar

5 

Okamoto E, Kikuchi K, Miyazaki Y, González-Alva P, Oku Y, Tanaka A, Yoshida N, Fujinami M, Ide F, Sakashita H and Kusama K: Significance of podoplanin expression in keratocystic odontogenic tumor. J Oral Pathol Med. 39:110–114. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Myoung H, Hong SP, Hong SD, Lee JI, Lim CY, Choung PH, Lee JH, Choi JY, Seo BM and Kim MJ: Odontogenic keratocyst: Review of 256 cases for recurrence and clinicopathologic parameters. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 91:328–333. 2001. View Article : Google Scholar : PubMed/NCBI

7 

Selvi F, Tekkesin MS, Cakarer S, Isler SC and Keskin C: Keratocystic odontogenic tumors: Predictive factors of recurrence by Ki67 and AgNOR labelling. Int J Med Sci. 9:262–268. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Kuroyanagi N, Sakuma H, Miyabe S, Machida J, Kaetsu A, Yokoi M, Maeda H, Warnakulasuriya S, Nagao T and Shimozato K: Prognostic factors for keratocystic odontogenic tumor (odontogenic keratocyst): Analysis of clinico-pathologic and immunohistochemical findings in cysts treated by enucleation. J Oral Pathol Med. 38:386–392. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Jamshidi S, Zargaran M, Baghaei F, Shojaei S, Zare Mahmoodabadi R, Dehghan A and Moghimbeigi A: An immunohistochemical survey to evaluate the expression of CD105 and CD34 in ameloblastoma and odontogenic keratocyst. J Dent (Shiraz). 15:192–198. 2014.PubMed/NCBI

10 

Naruse T, Kawasaki G, Yanamoto S, Mizuno A and Umeda M: Immunohistochemical study of VEGF expression in oral squamous cell carcinomas: Correlation with the mTOR-HIF-1α pathway. Anticancer Res. 31:4429–4437. 2011.PubMed/NCBI

11 

Yuan P, Temam S, El-Naggar A, Zhou X, Liu DD, Lee JJ and Mao L: Overexpression of podoplanin in oral cancer and its association with poor clinical outcome. Cancer. 107:563–569. 2006. View Article : Google Scholar : PubMed/NCBI

12 

Friedrich RE, Scheuer HA and Zustin J: Expression of podoplanin in nevoid basal cell carcinoma syndrome-associated keratocystic odontogenic tumours. Anticancer Res. 32:2125–2128. 2012.PubMed/NCBI

13 

Tsuneki M, Maruyama S, Yamazaki M, Cheng J and Saku T: Podoplanin expression profiles characteristic of odontogenic tumor-specific tissue architectures. Pathol Res Pract. 208:140–146. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Evans DG and Farndon PA: Nevoid basal cell carcinoma syndrome. GeneReviews®. Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH and Stephens K: University of Washington. (Seattle, USA). 2015.

15 

Agaram NP, Collins BM, Barnes L, Lomago D, Aldeeb D, Swalsky P, Finkelstein S and Hunt JL: Molecular analysis to demonstrate that odontogenic keratocysts are neoplastic. Arch Pathol Lab Med. 128:313–317. 2004.PubMed/NCBI

16 

Soluk Tekkeşın M, Mutlu S and Olgaç V: Expressions of bax, bcl-2 and ki-67 in odontogenic keratocysts (keratocystic odontogenic tumor) in comparison with ameloblastomas and radicular cysts. Turk Patoloji Derg. 28:49–55. 2012.PubMed/NCBI

17 

Yanamoto S, Kawasaki G, Yoshitomi I and Mizuno A: Expression of p53R2, newly p53 target in oral normal epithelium, epithelial dysplasia and squamous cell carcinoma. Cancer Lett. 190:233–243. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Toi M, Matsumoto T and Bando H: Vascular endothelial growth factor: Its prognostic, predictive, and therapeutic implications. Lancet Oncol. 2:667–673. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Carmeliet P and Jain RK: Angiogenesis in cancer and other diseases. Nature. 407:249–257. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Alaeddini M, Mostafaloo E, Mirmohammadkhani O, Eshghyar N and Etemad-Moghadam S: Exploring the concept of ‘inflammatory angiogenesis’ in keratocystic odontogenic tumor. Med Oral Patol Oral Cir Bucal. 18:e241–e245. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Zhang X, Wang J, Ding X, Xing S, Zhang W and Wang L, Wu H and Wang L: Altered expression of podoplanin in keratocystic odontogenic tumours following decompression. Oncol Lett. 7:627–630. 2014.PubMed/NCBI

22 

González-Alva P, Tanaka A, Oku Y, Yoshizawa D, Itoh S, Sakashita H, Ide F, Tajima Y and Kusama K: Keratocystic odontogenic tumor: A retrospective study of 183 cases. J Oral Sci. 50:205–212. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Chirapathomsakul D, Sastravaha P and Jansisyanont P: A review of odontogenic keratocysts and the behavior of recurrences. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 101:5–10. 2006. View Article : Google Scholar : PubMed/NCBI

24 

Morgan TA, Burton CC and Qian F: A retrospective review of treatment of the odontogenic keratocyst. J Oral Maxillofac Surg. 63:635–639. 2005. View Article : Google Scholar : PubMed/NCBI

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APA
Naruse, T., Yamashita, K., Yanamoto, S., Rokutanda, S., Matsushita, Y., Sakamoto, Y. ... Umeda, M. (2017). Histopathological and immunohistochemical study in keratocystic odontogenic tumors: Predictive factors of recurrence. Oncology Letters, 13, 3487-3493. https://doi.org/10.3892/ol.2017.5905
MLA
Naruse, T., Yamashita, K., Yanamoto, S., Rokutanda, S., Matsushita, Y., Sakamoto, Y., Sakamoto, H., Ikeda, H., Ikeda, T., Asahina, I., Umeda, M."Histopathological and immunohistochemical study in keratocystic odontogenic tumors: Predictive factors of recurrence". Oncology Letters 13.5 (2017): 3487-3493.
Chicago
Naruse, T., Yamashita, K., Yanamoto, S., Rokutanda, S., Matsushita, Y., Sakamoto, Y., Sakamoto, H., Ikeda, H., Ikeda, T., Asahina, I., Umeda, M."Histopathological and immunohistochemical study in keratocystic odontogenic tumors: Predictive factors of recurrence". Oncology Letters 13, no. 5 (2017): 3487-3493. https://doi.org/10.3892/ol.2017.5905