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MIB-1 expression in odontogenic epithelial rests, epithelium of healthy oral mucosa and epithelium of selected odontogenic cysts
Int. J. Oral Maxillofac. Surg. 2005; 34: 432–435 doi:10.1016/j.ijom.2004.09.005, available online at http://www.sciencedirect.com
Research and Emerging Technologies Oral Pathology
MIB-1 expression in odontogenic epithelial rests, epithelium of healthy oral mucosa and epithelium of selected odontogenic cysts An immunohistochemical study
U. Sarac¸og˘lu1, B. Kurt2, ¨ Gu¨nhan2, O. Gu¨ven3 O 1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Kırıkkale, Kırıkkale, Turkey; 2Department of Pathology, Gu¨lhane Military Medical School, Ankara, Turkey; 3Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Ankara, Ankara, Turkey
U. Sarac¸og˘lu, B. Kurt, . Gu¨nhan, O. Gu¨ven:MIB-1 expression in odontogenic epithelial rests, epithelium of healthy oral mucosa and epithelium of selected odontogenic cysts An immunohistochemical study. Int. J. Oral Maxillofac. Surg. 2005; 34: 432–435. # 2004 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. The aim of this study is to investigate the proliferative potential of rests of odontogenic epithelium found in follicles of unerupted teeth, epithelium of oral mucosa and epithelial linings of various odontogenic cysts. MIB-1 expression was studied in the rests of odontogenic epithelium (n = 10), healthy oral mucosa (n = 10), odontogenic keratocysts (n = 10) and other odontogenic cysts (n = 10) using an avidin–biotin peroxidase technique on paraffin sections. The number of positively stained cells was counted on 10 representative areas of epithelium using a 40 objective. The average number of MIB-1 positive cells in each group was calculated. No MIB-1 positive cells were seen in the rests of odontogenic epithelium. The mean numbers of MIB-1 positive cells detected within the epithelium of oral mucosa, and of radicular and dentigerous cysts were similar. The number of MIB-1 positive cells was found to be increased in the presence of marked inflammatory cell infiltration. The highest number of MIB-1 positive cells was seen in the keratocysts. These findings suggest that removal of an unerupted tooth to prevent the possibility of neoplastic transformation of rests of odontogenic epithelium is not a justifiable rationale.
Epithelial tumors and odontogenic cysts are derived from various types of epithelial cells in the oral tissues. These include remnants of odontogenic epithelium, the 0901-5027/040432+04 $30.00/0
epithelial lining of dental follicles and surface epithelium lining the oral mucosa. Numerous studies have indicated that there are differences in the proliferation
Key words: MIB-1; odontogenic epithelial rest; odontogenic cyst; immunohistochemistry. Accepted for publication 6 September 2004 Available online 10 November 2004
rates of various oral epithelial cells which may be important in the pathogenesis of epithelial tumors and odontogenic cysts8,9,14–16,19,21,26.
# 2004 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
MIB-1 expression in odontogenic epithelial rests The proliferative potential of rests of odontogenic epithelial cells found in dental follicles of unerupted teeth has not yet been investigated in detail. Uncertainty in this regard has been the foundation of one of the arguments in favor of surgical intervention for unerupted teeth. The odontogenic keratocyst (OKC), exhibits more aggressive behavior as compared to other odontogenic cysts. This has led to a number of studies investigating possible differences among various cyst linings14,16,20,26,27. Results of the latter studies indicate that the epithelial linings of keratocysts may have increased growth potential that is lacking in other types of odontogenic cyst linings3,13,14,18,27. For this reason, the OKC has also been called a ‘‘cystic tumor’’ by some authors. Immunohistochemical demonstration of proliferation-related markers is a valuable method for showing the proliferative potential of cells. A monoclonal antibody (MIB-1), which recognizes the epitope of Ki-67 antigen, is considered to be a reliable marker of proliferating cells. It is not expressed in quiescent cells. The aim of this study is to investigate the comparative proliferation potential of rests of odontogenic epithelium found in dental follicles of unerupted teeth, epithelium of oral mucosa and epithelial linings of various odontogenic cysts. The proliferation potential of these respective epithelial cells may have some bearing on strategies taken for surgical intervention.
433
Table 1. Number of MIB-1 positive cells for each case (MIB-1 positive cells were counted in 10 high power field) Group 1: rests of odontogenic epithelium No MIB-1 positive cell
*
Group 2: healthy oral mucosa 9 8 11* 5 7 8 8 9 7
Group 3: keratocysts 160 170 200 200 210 170 110 80 90
Group 4: odontogenic cysts 7 22* 12* 8 13* 8 9 11* 11*
These cases have inflammatory cells.
calculated. The density of inflammatory cell infiltration in the surrounding tissues was semiquantitatively graded as ‘‘none’’, ‘‘mild to moderate’’ and ‘‘intense’’.
(Fig. 3), primarily in the basal and parabasal epithelial layers. Discussion
Results
The arithmetical mean number of MIB-1 positive cells in each group is shown in Table 1. No MIB-1 positive cells were seen in rests of odontogenic epithelium (Fig. 1) and the mean numbers of MIB-1 positive cells detected within the epithelium of oral mucosa and within the epithelium of radicular and dentigerous cysts were similar. MIB-1 positive cells were seen only in the basal epithelial cell layer. The number of MIB-1 positive cells was greater in association with significant inflammatory cell infiltration (Fig. 2). The highest number of MIB-1 positive cells were seen in the keratocyst group
In living organisms, there is continuous replacement of cells, with the exception of those in organs composed mostly of stable cells. The process of cell proliferation requires division of cells, which is under tight control of molecules expressed during the cell cycle. Disorganized and increased proliferation of cells occurs in various lesions, including cancer. Growth rate is one of the determinants of tumor aggressiveness. There are several indicators used for determining cell proliferation status1,4,7,11,12,22,25. These include the mitotic count, thymidine labeling index, bromodeoxyuridine incorporation, flow cytometry and immunohistochemical reactivity for various antibodies. Immunohis-
Materials and methods
Ten samples of dental follicles containing rests of odontogenic epithelium, 10 specimens of healthy oral mucosa, 10 cases of OKC and 10 cases of other odontogenic cysts (10 radicular, 10 dentigerous) constitute the material of this study. Oral mucosal samples were obtained during orthodontic or simple tooth extractions. Ten percent buffered formalin-fixed and paraffin-embedded tissue blocks of various odontogenic cysts and dental follicles were retrieved from the archives of The Department of Pathology of Gu¨ lhane Military Medical Academy. Four-micron thick sections were prepared. Slides were immunohistochemically stained with avidin–biotin peroxidase technique by using MIB-1 antibody (Neomarkers). DAB was used as chromogen and Mayers’ hematoxylin was the counterstain. The number of positively stained cells was counted on 10 representative areas of epithelium using a 40 objective. The average number of MIB-1 positive cells in each group was
Fig. 1. No MIB-1 positive cells were seen in the rests of odontogenic epithelium (400).
434
Sarac¸og˘ lu et al.
Fig. 2. MIB-1 positive cells (arrows) were seen in inflammed odontogenic epithelium (200).
Fig. 3. Odontogenic keratocyst epithelium showing large numbers of MIB-1 positive cells (arrows) (200).
tochemical studies using proliferation markers have focused on antibodies like Ki-67, the Ki-67 clone MIB-1, and proliferating cell nuclear antigen (PCNA). These cell cycle-dependent antibodies are quite sensitive, and in particular the MIB-1 antibody has attained favor as a cell proliferation marker. MIB-1 is expressed in proliferating cells during the proliferating phase of the cell cycle, but is not expressed during the resting phase. MIB-1 has been used to investigate the proliferation potential of normal tissues, as well as preneoplastic and neoplastic lesions6,8,9,17,21. The identification of abnormally increased proliferation of precursor cells is an important aspect of neoplastic progression9. The lack of data concerning proliferation potential of odontogenic epithelial rests found in dental follicles of unerupted teeth is a source of controversy concerning surgical removal of unerupted teeth. However, it is also believed that cysts and tumors of the oral cavity could arise from remnants of odontogenic epithelium found in other oral tissues5,10,23. ALDESPERGER et al.2 using PCNA, reported that cells of dental follicle epithelium in asymptomatic dental follicular specimens were apparently at rest. The results of our study demonstrate that odontogenic epithelial rests found in dental follicles of unerupted teeth contained no MIB-1 expressing cells. These findings suggest that removal of an unerupted tooth in order to obviate the presumed risk of neoplastic proliferation originating from the remnants of odontogenic epithelium may not be justified. However, there may still be other reasons for their removal. It is known that the proliferative capacity of oral mucosal epithelium is notably dynamic in that it regularly regenerates itself on a relatively rapid basis. However, in the present study, epithelial cells from healthy oral mucosal specimens showed relatively rare MIB-1 expression. An increased proliferative marker expression was noted in the presence of heavy subepithelial inflammatory cell infiltration. It has been reported that chronic irritation such as that caused by chronic inflammation may stimulate proliferation of oral epithelial cells13,19,24. In this study, the MIB-1 expressions of oral mucosal epithelium and of the epithelial linings of cysts were similar. A higher number of MIB-1 positive cells in odontogenic cyst epithelium and oral mucosal epithelium with subepithelial inflammatory cell infiltrates support the view that ‘‘the number of cycling epithelial cells may increase as a
MIB-1 expression in odontogenic epithelial rests consequence of inflammatory stimulation’’24. The growth rates of epithelial lining of various types of odontogenic cysts seem to differ. Keratocysts, known for their aggressiveness, contained significantly higher numbers of MIB-1 positive cells than the lining of the other odontogenic cysts. Further investigations on genomic changes are needed to understand fully the proliferation potentials of different types of epithelial cells that participate in formation of various odontogenic lesions.
References 1. Alberts B, Bray D, Lewis J, Raff M, Robert K, Watson JD. Molecular biology of the cell. 2nd edn. New York: Garland Publishing Inc. 1989 : 424–426. 2. Aldesperger J, Cambell JH, Coates DB, Summerline DJ, Tomich CE. Early soft tissue pathosis associated with impacted third molars without pericoronal radiolucency. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000: 89: 402–406. 3. Browne RM. The odontogenic keratocyst. Histological features and their correlation with clinical behaviour. Br Dent J 1971: 131: 249–259. 4. Burns B, Curry RH, Bell MEA. Morphological features of prognostic significance in uterine smooth muscle tumors: a review of eighty four cases. Am J Obstet Gynecol 1979: 135: 109–114. 5. Curran AE, Damm DD, Drummond JF. Pathologically significant pericoronal lesions in adults: histopathologic evaluation. J Oral Maxillofac Surg 2002: 60: 613–617. 6. Duchrow M, Schluter C, Key G, Kubbutat MH, Wohlenberg C, Flad HD, Gerdes J. Cell proliferation-associated nuclear antigen defined by antibody Ki-67: a new kind of cell cyclemaintaining proteins. Arch Immunol Ther Exp Warsz 1995: 43: 117–121.
7. Dunphy WG, Newport JW. Unravelling of mitotic control mechanisms. Cell 1988: 55: 925–928. 8. Girod SC, Krueger G, Pape HD. p53 and Ki 67 expression in preneoplastic and neoplastic lesions of the oral mucosa. Int J Oral Maxillofac Surg 1993: 22: 285–288. 9. Girod SC, Pfeiffer P, Ries J, Pape HD. Proliferative activity and loss of function of tumour suppressor genes as ‘biomarkers’ in diagnosis and prognosis of benign and preneoplastic oral lesions and oral squamous cell carcinoma. Br J Oral Maxillofac Surg 1998: 36: 252–260. 10. Glosser JW, Campbell JH. Pathologic change in soft tissues associated with radiographically ‘normal’ third molar impactions. Br J Oral Maxillofac Surg 1999: 37: 259–260. 11. Hall PA, Levison DA. Review: assessment of cell proliferation in histological material. J Clin Pathol 1990: 43: 184– 192. 12. Lee MG, Nurse P. Cell cycle control genes in fission yeast and mammalian cells. Trends Genet 1988: 4: 287–290. 13. Li TJ, Browne RM, Matthews JB. Expression of epidermal growth factor receptors by odontogenic jaw cysts. Virchows Arch 1993: 423: 137–144. 14. Li TJ, Browne RM, Matthews JB. Quantification of PCNA positive cells within odontogenic jaw cyst epithelium. J Oral Pathol Med 1994: 23: 184–189. 15. Li TJ, Browne RM, Matthews JB. Epithelial cell proliferation in odontogenic keratocysts: a comparative immunocytochemical study of Ki67 in simple, recurrent and basal cell nevus syndrome (BCNS)-associated lesions. J Oral Pathol Med 1995: 24: 221–226. 16. Li TJ, Browne RM, Prime SS, Paterson JC, Matthews JB. p53 expression in odontogenic keratocyst epithelium. J Oral Pathol Med 1996: 25: 249–255. 17. Macluskey M, Ogden GR, Green M, Crisholm DM, Schor SL, Schor AM. The association between epithelial proliferation and disease progression in the oral mucosa. Oral Oncol 1999: 35: 409–414. 18. Matthews JB, Mason GI, Browne RM. Epithelial cell markers and prolifer-
19.
20.
21.
22.
23.
24.
25.
26.
27.
435
ating cells in odontogenic jaw cysts. J Pathol 1988: 156: 283–290. Paula AMB, Carvalhais JN, Dominques MG, Barreto DC, Mesquita RA. Cell proliferation markers in the odontogenic keratocysts: effect of inflammation. J Oral Pathol Med 2000: 29: 477–482. Piattelli A, Fioroni M, Santinelli A, Rubini C. p53 protein expression in odontogenic cysts. J Endodont 2001: 27: 459–461. Piattelli A, Rubini C, Fioroni M, Lezzi G, Santinelli A. Prevalence of p53, bcl-2 and Ki-67 immunoreactivity and of apoptosis in normal oral epithelium and in premalignant and malignant lesions of the oral cavity. J Oral Maxillofac Surg 2002: 60: 532–540. Quinn CM, Wright NA. The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applicatios as prognostic variables. J Pathol 1990: 160: 93–102. Rakprasitkul S. Pathologic changes in the pericoronal tissues of unerupted third molars. Quintessence Int 2001: 32: 633– 638. Rodu B, Tate AL, Martinez Jr MG. The implications of inflammation in odontogenic keratocysts. J Oral Pathol Med 1987: 16: 518–521. Schliephake H. Prognostic relevance of molecular markers of oral cancer-a review. Int J Oral Maxillofac Surg 2003: 32: 233–245. Slootweg PJ. p53 protein and Ki-67 reactivity in epithelial odontogenic lesions. An immunohistochemical study. J Oral Pathol Med 1995: 24: 393–397. Stoelinga PJ... Long-term follow-up on keratocysts treated according to a defined protocol. Int J Oral Maxillofac Surg 2001: 30: 14–25.
Address: Orhan Gu¨ven Yesilyurt sokak No: 24/15 06690 Asagi Ayranci Ankara Turkey. Fax: +90 312 2123954 E-mail: [email protected]
Research and Emerging Technologies Oral Pathology
MIB-1 expression in odontogenic epithelial rests, epithelium of healthy oral mucosa and epithelium of selected odontogenic cysts An immunohistochemical study
U. Sarac¸og˘lu1, B. Kurt2, ¨ Gu¨nhan2, O. Gu¨ven3 O 1 Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Kırıkkale, Kırıkkale, Turkey; 2Department of Pathology, Gu¨lhane Military Medical School, Ankara, Turkey; 3Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, University of Ankara, Ankara, Turkey
U. Sarac¸og˘lu, B. Kurt, . Gu¨nhan, O. Gu¨ven:MIB-1 expression in odontogenic epithelial rests, epithelium of healthy oral mucosa and epithelium of selected odontogenic cysts An immunohistochemical study. Int. J. Oral Maxillofac. Surg. 2005; 34: 432–435. # 2004 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Abstract. The aim of this study is to investigate the proliferative potential of rests of odontogenic epithelium found in follicles of unerupted teeth, epithelium of oral mucosa and epithelial linings of various odontogenic cysts. MIB-1 expression was studied in the rests of odontogenic epithelium (n = 10), healthy oral mucosa (n = 10), odontogenic keratocysts (n = 10) and other odontogenic cysts (n = 10) using an avidin–biotin peroxidase technique on paraffin sections. The number of positively stained cells was counted on 10 representative areas of epithelium using a 40 objective. The average number of MIB-1 positive cells in each group was calculated. No MIB-1 positive cells were seen in the rests of odontogenic epithelium. The mean numbers of MIB-1 positive cells detected within the epithelium of oral mucosa, and of radicular and dentigerous cysts were similar. The number of MIB-1 positive cells was found to be increased in the presence of marked inflammatory cell infiltration. The highest number of MIB-1 positive cells was seen in the keratocysts. These findings suggest that removal of an unerupted tooth to prevent the possibility of neoplastic transformation of rests of odontogenic epithelium is not a justifiable rationale.
Epithelial tumors and odontogenic cysts are derived from various types of epithelial cells in the oral tissues. These include remnants of odontogenic epithelium, the 0901-5027/040432+04 $30.00/0
epithelial lining of dental follicles and surface epithelium lining the oral mucosa. Numerous studies have indicated that there are differences in the proliferation
Key words: MIB-1; odontogenic epithelial rest; odontogenic cyst; immunohistochemistry. Accepted for publication 6 September 2004 Available online 10 November 2004
rates of various oral epithelial cells which may be important in the pathogenesis of epithelial tumors and odontogenic cysts8,9,14–16,19,21,26.
# 2004 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
MIB-1 expression in odontogenic epithelial rests The proliferative potential of rests of odontogenic epithelial cells found in dental follicles of unerupted teeth has not yet been investigated in detail. Uncertainty in this regard has been the foundation of one of the arguments in favor of surgical intervention for unerupted teeth. The odontogenic keratocyst (OKC), exhibits more aggressive behavior as compared to other odontogenic cysts. This has led to a number of studies investigating possible differences among various cyst linings14,16,20,26,27. Results of the latter studies indicate that the epithelial linings of keratocysts may have increased growth potential that is lacking in other types of odontogenic cyst linings3,13,14,18,27. For this reason, the OKC has also been called a ‘‘cystic tumor’’ by some authors. Immunohistochemical demonstration of proliferation-related markers is a valuable method for showing the proliferative potential of cells. A monoclonal antibody (MIB-1), which recognizes the epitope of Ki-67 antigen, is considered to be a reliable marker of proliferating cells. It is not expressed in quiescent cells. The aim of this study is to investigate the comparative proliferation potential of rests of odontogenic epithelium found in dental follicles of unerupted teeth, epithelium of oral mucosa and epithelial linings of various odontogenic cysts. The proliferation potential of these respective epithelial cells may have some bearing on strategies taken for surgical intervention.
433
Table 1. Number of MIB-1 positive cells for each case (MIB-1 positive cells were counted in 10 high power field) Group 1: rests of odontogenic epithelium No MIB-1 positive cell
*
Group 2: healthy oral mucosa 9 8 11* 5 7 8 8 9 7
Group 3: keratocysts 160 170 200 200 210 170 110 80 90
Group 4: odontogenic cysts 7 22* 12* 8 13* 8 9 11* 11*
These cases have inflammatory cells.
calculated. The density of inflammatory cell infiltration in the surrounding tissues was semiquantitatively graded as ‘‘none’’, ‘‘mild to moderate’’ and ‘‘intense’’.
(Fig. 3), primarily in the basal and parabasal epithelial layers. Discussion
Results
The arithmetical mean number of MIB-1 positive cells in each group is shown in Table 1. No MIB-1 positive cells were seen in rests of odontogenic epithelium (Fig. 1) and the mean numbers of MIB-1 positive cells detected within the epithelium of oral mucosa and within the epithelium of radicular and dentigerous cysts were similar. MIB-1 positive cells were seen only in the basal epithelial cell layer. The number of MIB-1 positive cells was greater in association with significant inflammatory cell infiltration (Fig. 2). The highest number of MIB-1 positive cells were seen in the keratocyst group
In living organisms, there is continuous replacement of cells, with the exception of those in organs composed mostly of stable cells. The process of cell proliferation requires division of cells, which is under tight control of molecules expressed during the cell cycle. Disorganized and increased proliferation of cells occurs in various lesions, including cancer. Growth rate is one of the determinants of tumor aggressiveness. There are several indicators used for determining cell proliferation status1,4,7,11,12,22,25. These include the mitotic count, thymidine labeling index, bromodeoxyuridine incorporation, flow cytometry and immunohistochemical reactivity for various antibodies. Immunohis-
Materials and methods
Ten samples of dental follicles containing rests of odontogenic epithelium, 10 specimens of healthy oral mucosa, 10 cases of OKC and 10 cases of other odontogenic cysts (10 radicular, 10 dentigerous) constitute the material of this study. Oral mucosal samples were obtained during orthodontic or simple tooth extractions. Ten percent buffered formalin-fixed and paraffin-embedded tissue blocks of various odontogenic cysts and dental follicles were retrieved from the archives of The Department of Pathology of Gu¨ lhane Military Medical Academy. Four-micron thick sections were prepared. Slides were immunohistochemically stained with avidin–biotin peroxidase technique by using MIB-1 antibody (Neomarkers). DAB was used as chromogen and Mayers’ hematoxylin was the counterstain. The number of positively stained cells was counted on 10 representative areas of epithelium using a 40 objective. The average number of MIB-1 positive cells in each group was
Fig. 1. No MIB-1 positive cells were seen in the rests of odontogenic epithelium (400).
434
Sarac¸og˘ lu et al.
Fig. 2. MIB-1 positive cells (arrows) were seen in inflammed odontogenic epithelium (200).
Fig. 3. Odontogenic keratocyst epithelium showing large numbers of MIB-1 positive cells (arrows) (200).
tochemical studies using proliferation markers have focused on antibodies like Ki-67, the Ki-67 clone MIB-1, and proliferating cell nuclear antigen (PCNA). These cell cycle-dependent antibodies are quite sensitive, and in particular the MIB-1 antibody has attained favor as a cell proliferation marker. MIB-1 is expressed in proliferating cells during the proliferating phase of the cell cycle, but is not expressed during the resting phase. MIB-1 has been used to investigate the proliferation potential of normal tissues, as well as preneoplastic and neoplastic lesions6,8,9,17,21. The identification of abnormally increased proliferation of precursor cells is an important aspect of neoplastic progression9. The lack of data concerning proliferation potential of odontogenic epithelial rests found in dental follicles of unerupted teeth is a source of controversy concerning surgical removal of unerupted teeth. However, it is also believed that cysts and tumors of the oral cavity could arise from remnants of odontogenic epithelium found in other oral tissues5,10,23. ALDESPERGER et al.2 using PCNA, reported that cells of dental follicle epithelium in asymptomatic dental follicular specimens were apparently at rest. The results of our study demonstrate that odontogenic epithelial rests found in dental follicles of unerupted teeth contained no MIB-1 expressing cells. These findings suggest that removal of an unerupted tooth in order to obviate the presumed risk of neoplastic proliferation originating from the remnants of odontogenic epithelium may not be justified. However, there may still be other reasons for their removal. It is known that the proliferative capacity of oral mucosal epithelium is notably dynamic in that it regularly regenerates itself on a relatively rapid basis. However, in the present study, epithelial cells from healthy oral mucosal specimens showed relatively rare MIB-1 expression. An increased proliferative marker expression was noted in the presence of heavy subepithelial inflammatory cell infiltration. It has been reported that chronic irritation such as that caused by chronic inflammation may stimulate proliferation of oral epithelial cells13,19,24. In this study, the MIB-1 expressions of oral mucosal epithelium and of the epithelial linings of cysts were similar. A higher number of MIB-1 positive cells in odontogenic cyst epithelium and oral mucosal epithelium with subepithelial inflammatory cell infiltrates support the view that ‘‘the number of cycling epithelial cells may increase as a
MIB-1 expression in odontogenic epithelial rests consequence of inflammatory stimulation’’24. The growth rates of epithelial lining of various types of odontogenic cysts seem to differ. Keratocysts, known for their aggressiveness, contained significantly higher numbers of MIB-1 positive cells than the lining of the other odontogenic cysts. Further investigations on genomic changes are needed to understand fully the proliferation potentials of different types of epithelial cells that participate in formation of various odontogenic lesions.
References 1. Alberts B, Bray D, Lewis J, Raff M, Robert K, Watson JD. Molecular biology of the cell. 2nd edn. New York: Garland Publishing Inc. 1989 : 424–426. 2. Aldesperger J, Cambell JH, Coates DB, Summerline DJ, Tomich CE. Early soft tissue pathosis associated with impacted third molars without pericoronal radiolucency. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000: 89: 402–406. 3. Browne RM. The odontogenic keratocyst. Histological features and their correlation with clinical behaviour. Br Dent J 1971: 131: 249–259. 4. Burns B, Curry RH, Bell MEA. Morphological features of prognostic significance in uterine smooth muscle tumors: a review of eighty four cases. Am J Obstet Gynecol 1979: 135: 109–114. 5. Curran AE, Damm DD, Drummond JF. Pathologically significant pericoronal lesions in adults: histopathologic evaluation. J Oral Maxillofac Surg 2002: 60: 613–617. 6. Duchrow M, Schluter C, Key G, Kubbutat MH, Wohlenberg C, Flad HD, Gerdes J. Cell proliferation-associated nuclear antigen defined by antibody Ki-67: a new kind of cell cyclemaintaining proteins. Arch Immunol Ther Exp Warsz 1995: 43: 117–121.
7. Dunphy WG, Newport JW. Unravelling of mitotic control mechanisms. Cell 1988: 55: 925–928. 8. Girod SC, Krueger G, Pape HD. p53 and Ki 67 expression in preneoplastic and neoplastic lesions of the oral mucosa. Int J Oral Maxillofac Surg 1993: 22: 285–288. 9. Girod SC, Pfeiffer P, Ries J, Pape HD. Proliferative activity and loss of function of tumour suppressor genes as ‘biomarkers’ in diagnosis and prognosis of benign and preneoplastic oral lesions and oral squamous cell carcinoma. Br J Oral Maxillofac Surg 1998: 36: 252–260. 10. Glosser JW, Campbell JH. Pathologic change in soft tissues associated with radiographically ‘normal’ third molar impactions. Br J Oral Maxillofac Surg 1999: 37: 259–260. 11. Hall PA, Levison DA. Review: assessment of cell proliferation in histological material. J Clin Pathol 1990: 43: 184– 192. 12. Lee MG, Nurse P. Cell cycle control genes in fission yeast and mammalian cells. Trends Genet 1988: 4: 287–290. 13. Li TJ, Browne RM, Matthews JB. Expression of epidermal growth factor receptors by odontogenic jaw cysts. Virchows Arch 1993: 423: 137–144. 14. Li TJ, Browne RM, Matthews JB. Quantification of PCNA positive cells within odontogenic jaw cyst epithelium. J Oral Pathol Med 1994: 23: 184–189. 15. Li TJ, Browne RM, Matthews JB. Epithelial cell proliferation in odontogenic keratocysts: a comparative immunocytochemical study of Ki67 in simple, recurrent and basal cell nevus syndrome (BCNS)-associated lesions. J Oral Pathol Med 1995: 24: 221–226. 16. Li TJ, Browne RM, Prime SS, Paterson JC, Matthews JB. p53 expression in odontogenic keratocyst epithelium. J Oral Pathol Med 1996: 25: 249–255. 17. Macluskey M, Ogden GR, Green M, Crisholm DM, Schor SL, Schor AM. The association between epithelial proliferation and disease progression in the oral mucosa. Oral Oncol 1999: 35: 409–414. 18. Matthews JB, Mason GI, Browne RM. Epithelial cell markers and prolifer-
19.
20.
21.
22.
23.
24.
25.
26.
27.
435
ating cells in odontogenic jaw cysts. J Pathol 1988: 156: 283–290. Paula AMB, Carvalhais JN, Dominques MG, Barreto DC, Mesquita RA. Cell proliferation markers in the odontogenic keratocysts: effect of inflammation. J Oral Pathol Med 2000: 29: 477–482. Piattelli A, Fioroni M, Santinelli A, Rubini C. p53 protein expression in odontogenic cysts. J Endodont 2001: 27: 459–461. Piattelli A, Rubini C, Fioroni M, Lezzi G, Santinelli A. Prevalence of p53, bcl-2 and Ki-67 immunoreactivity and of apoptosis in normal oral epithelium and in premalignant and malignant lesions of the oral cavity. J Oral Maxillofac Surg 2002: 60: 532–540. Quinn CM, Wright NA. The clinical assessment of proliferation and growth in human tumours: evaluation of methods and applicatios as prognostic variables. J Pathol 1990: 160: 93–102. Rakprasitkul S. Pathologic changes in the pericoronal tissues of unerupted third molars. Quintessence Int 2001: 32: 633– 638. Rodu B, Tate AL, Martinez Jr MG. The implications of inflammation in odontogenic keratocysts. J Oral Pathol Med 1987: 16: 518–521. Schliephake H. Prognostic relevance of molecular markers of oral cancer-a review. Int J Oral Maxillofac Surg 2003: 32: 233–245. Slootweg PJ. p53 protein and Ki-67 reactivity in epithelial odontogenic lesions. An immunohistochemical study. J Oral Pathol Med 1995: 24: 393–397. Stoelinga PJ... Long-term follow-up on keratocysts treated according to a defined protocol. Int J Oral Maxillofac Surg 2001: 30: 14–25.
Address: Orhan Gu¨ven Yesilyurt sokak No: 24/15 06690 Asagi Ayranci Ankara Turkey. Fax: +90 312 2123954 E-mail: [email protected]