| Abstract|| |
Context: p53 and survivin are involved in cell cycle progression and inhibition of apoptosis, respectively. Survivin is a unique protein which functions in progression of cell division and inhibits apoptosis leading to cell proliferation and cell survival. According to the literature, mutation of p53 leads to promotion of survivin function. Thus, the importance of cell cycle aberration and uncontrolled proliferation resulting from mutation of p53 and up-regulation of survivin is discussed.
Aims: To assess the role of p53 and survivin in ameloblastoma and adenomatoid odontogenic tumor (AOT).
Settings and Design: The percentages of positive tumor cells were considered for statistical evaluation. Nuclear labeling index for p53 and nuclear, cytoplasmic and combined labeling index for survivin was obtained from the stained slides.
Materials and Methods: Immunohistochemical expression of p53 and survivin was done qualitatively and quantitatively in 25 cases each of ameloblastoma and AOT.
Statistical Analysis Used: Mann-Whitney U-test, Wilcoxon signed ranks test and Pearson's correlation test.
Results: Quantitatively, p53 and survivin expression was statistically significant in AOT (P = 0.003) and qualitatively, in ameloblastoma (P = 0.004). Survivin expression was significant (P = 0.002) between the study groups unlike that of p53 (P = 0.554).
Conclusions: There was no much difference in p53 expression in ameloblastoma and AOT suggestive of cell cycle aberration in both the odontogenic tumors, but significant difference in survivin expression in ameloblastoma and AOT with higher percentage of positive cells in ameloblastoma may be indicative of an aggressive behavior of ameloblastoma.
Keywords: Adenomatoid odontogenic tumor, ameloblastoma, immunohistochemical expression, p53, survivin
|How to cite this article:|
Shaikh Z, Niranjan K C. Cell cycle aberration in ameloblastoma and adenomatoid odontogenic tumor: As evidenced by the expression of p53 and survivin. Indian J Dent Res 2015;26:565-70
A series of genetic and molecular alterations appear to promote the development and progression of tumors.  Several studies have reported differences in the proliferative potential of odontogenic epithelial cells, with significant impact on the formation of odontogenic tumor.  Many proteins are involved in cell processes such as proliferation, differentiation and apoptosis.  Regulation of the cell cycle and control of apoptosis are thought to be intimately linked processes. 
|How to cite this URL:|
Shaikh Z, Niranjan K C. Cell cycle aberration in ameloblastoma and adenomatoid odontogenic tumor: As evidenced by the expression of p53 and survivin. Indian J Dent Res [serial online] 2015 [cited 2019 Jul 18];26:565-70. Available from: http://www.ijdr.in/text.asp?2015/26/6/565/176916
Ameloblastoma is the second most common odontogenic tumor arising from odontogenic epithelium and is characterized by a benign but locally aggressive behavior, with a high risk of recurrence.  Adenomatoid odontogenic tumor (AOT) is an uncommon benign odontogenic tumor characterized histologically by sheets, whorls, rosettes and duct-like pattern of tumor cells.  Its nature as a neoplasm or hamartoma is still a subject of diverging opinions based on clinical observations and has little scientific evidence. 
p53, a tumor suppressor gene is located on the short arm of chromosome 17pl3.1.  When DNA has sustained damage, p53 activates DNA repair proteins by inducing cell cycle arrest at the G1/S regulation point and initiates apoptosis if DNA damage is irreparable,  thereby playing a critical role in both cell cycle progression and induction of apoptosis.  Survivin, a member of inhibitor of apoptosis protein family, is localized to chromosome 17q25.  It is a unique bifunctional protein which suppresses apoptosis by inhibiting caspase-3 and caspase-9 and regulates G2/M phase of the cell cycle by associating with mitotic spindle microtubules. It is highly expressed in embryonic tissues and neoplasms but absent in terminally differentiated cells. 
Several studies have proposed that the subcellular distribution of survivin is regulated by active import into the nucleus and chromosomal maintenance 1 (CRM1)-mediated export to the cytoplasm. ,, Recent studies have suggested that the nuclear pool of survivin is involved in promoting cell proliferation, whereas the cytoplasmic pool of survivin controls cell survival. ,,,
Survivin is known to be repressed by wild-type p53. , The upregulation of survivin with mutation of p53 in cell cycle is generally well known, , but data describing the expression pattern and the role of p53 and survivin in odontogenic tumors is limited. Thus, in the present study, p53 and survivin expression both nuclear and cytoplasmic was assessed in ameloblastoma and AOT by immunohistochemistry for a better insight into their biological behavior.
| Materials and Methods|| |
A retrospective immunohistochemical study was done with a sample size of 50 consisting 25 cases each of ameloblastoma and AOT. The study was approved by the Institutional Ethics Committee. About 4 μm sections of the paraffin embedded tissue blocks were taken on 3-aminopropyl triethoxysilane coated slides. The tissue sections were deparaffinized in xylene, rehydrated in a decreasing isopropyl alcohol series and antigen retrieval was done with ethylenediaminetetraacetic acid buffer (pH 8.0). A super sensitive polymer horseradish peroxidase detection system, a biotin free detection system supplied by Biogenex life sciences limited (California, USA) was followed. Primary survivin rabbit monoclonal antibody (Clone EP28880Y, immunoglobulin [IgG]; Biogenex Ltd., USA; diluted at 1:40) and p53 protein mouse monoclonal antibody (Clone DO7, IgG2b; Biogenex Ltd., USA; diluted at 1:150) was applied to detect survivin and p53 proteins, respectively. The sections were treated with diaminobenzene chromogen and counterstained with Harri's hematoxylin. Ten tooth germs from postmortem fetal oral tissues were taken as control and prepared in similar manner as that of the sample tissues.
All immunostained slides were separately examined by two oral pathologists using a binocular optical microscope, and no interobserver variability was observed. The staining intensity was assessed by grading on a four point scale as "0" for negative staining, "1" for mild staining, "2" for moderate staining and "3" for intense staining. The expression of p53 and survivin was quantitatively assessed by counting the number of positive tumor cells among 400 tumor cells in the region of highest expression using an eye-piece occulometer grid at an objective magnification of ×40. The results were multiplied by 100 and were expressed as the percentage of positive cells.  Nuclear expression of survivin (A) and cytoplasmic expression of survivin (B) was assessed separately. The data were statistically analyzed by Mann-Whitney U-test, Wilcoxon signed ranks test and Pearson's correlation test. A P < 0.05 was considered as statistically significant.
| Results|| |
Expression was evident as a brown color in the cell nucleus for p53 and in the nucleus (A) and/or cytoplasm (B) for survivin. Out of ten tooth germs, four showed expression for both p53 and survivin; two tooth germs showed only p53 expression and one tooth germ showed only survivin expression. In three tooth germs, neither p53 nor survivin expression was evident. p53 staining was observed in inner enamel epithelium (IEE) and the staining intensity was predominantly moderate [Figure 1]a. Staining intensity for survivin was mild to moderate with cytoplasmic expression in IEE, stellate reticulum and outer enamel epithelium with focal nuclear staining in IEE [Figure 1]b. The percentage of p53 positive cells ranged from 0% to 85%, while survivin (A and B) positive cells ranged from 0% to 86% with average percentage of 24.89% and 29.1%, respectively [Table 1] and [Table 2]. A significant positive correlation was found between p53 and survivin in tooth germs (r = 0.793, P = 0.006).
|Figure 1: Intense p53 and survivin expression in tooth germ. (a) Intense p53 expression in tooth germ (×10). p53 nuclear expression in inner enamel epithelial cells (×40) (immunostaining: Diaminobenzene chromogen, p53 monoclonal antibody). (b) Intense survivin expression in tooth germ (×10). Survivin cytoplasmic expression in inner enamel epithelial cells, stellate reticulum and outer enamel epithelial cells with focal nuclear expression in inner enamel epithelial cells (×40) (immunostaining: Diaminobenzene chromogen, survivin monoclonal antibody)|
Click here to view
|Table 1: Qualitative and quantitative analysis of p53 expression in tooth germ, ameloblastoma and adenomatoid odontogenic tumor |
Click here to view
|Table 2: Qualitative and quantitative analysis of survivin expression in tooth germ, ameloblastoma and adenomatoid odontogenic tumor |
Click here to view
The 25 cases of ameloblastoma included 14 men and 11 women. The mean age of occurrence was 28.76 years. p53 expression was seen in peripheral ameloblast-like and few central stellate reticulum-like cells [Figure 2]a. Survivin expression was predominantly cytoplasmic (B), seen in both peripheral ameloblast-like and central stellate reticulum-like cells with only focal nuclear expression (A) in peripheral ameloblast-like cells [Figure 2]b. A positive correlation was observed between p53 and survivin in ameloblastoma (r = 0.251; P = 0.226).
|Figure 2: Moderate p53 and survivin expression in follicular ameloblastoma. (a) Moderate p53 expression in follicular ameloblastoma (×10). p53 nuclear expression in ameloblast-like cells and stellate reticulum-like cells (×40) (immunostaining: Diaminobenzene chromogen, p53 monoclonal antibody). (b) Moderate survivin expression in follicular ameloblastoma (×10). Survivin cytoplasmic expression in ameloblast-like cells and stellate reticulum-like cells with focal nuclear expression in peripheral cells (×40) (immunostaining: Diaminobenzene chromogen, survivin monoclonal antibody)|
Click here to view
AOT sample included seven men and 18 women with mean age of 19.4 years. p53 and survivin expression was present predominantly in the cells forming whorls, lining duct-like structures and rosettes [Figure 3]a and b. Survivin expression was predominantly cytoplasmic with few cells showing nuclear staining. Statistically significant positive correlation was observed between p53 and survivin expression in AOT (r = 0.846; P = 0.000).
|Figure 3: Intense p53 and survivin expression in adenomatoid odontogenic tumor. (a) Intense p53 expression in whorls, rosette and duct-like structure in adenomatoid odontogenic tumor (×10). p53 nuclear expression in duct-like structure with no expression in spindle shaped cells (×40) (immunostaining: Diaminobenzene chromogen, p53 monoclonal antibody). (b) Intense survivin expression in whorls, rosette and duct-like structure in adenomatoid odontogenic tumor (×10). Survivin cytoplasmic expression in rosette (×40) (immunostaining: Diaminobenzene chromogen, survivin monoclonal antibody)|
Click here to view
[Table 1] and [Table 2] summarize the staining intensity and number of positively stained p53 and survivin cells in ameloblastoma and AOT, respectively. The percentage of p53 positive cells ranged from 56% to 98% with an average percentage of 75.97% in ameloblastoma and 33-93% with an average percentage of 69.87% in AOT. The percentage of survivin positive cells ranged from 63% to 97% with an average percentage of 78.25% in ameloblastoma and 29-86% with an average percentage of 62.94% in AOT. p53 staining was predominantly intense in ameloblastoma and AOT, survivin staining was predominantly moderate in ameloblastoma and AOT, but no significance was seen between the study groups. Quantitatively, there was no significant difference in p53 expression between ameloblastoma and AOT, but significance was observed in survivin expression between the two groups [Table 3]. Nuclear and cytoplasmic survivin expression in ameloblastoma and AOT was not significant (P = 0.076 and P = 0.031) due to focal survivin nuclear positivity.
|Table 3: Pair wise comparison of p53 and survivin expression in ameloblastoma and adenomatoid odontogenic tumor by Mann-Whitney U-test |
Click here to view
Wilcoxon signed ranks test showed a significant difference in p53 and survivin expression in AOT quantitatively, but with respect to staining intensity significant difference was observed in ameloblastoma [Table 4].
|Table 4: Qualitative and quantitative analysis of p53 and survivin (A and B) expression in each study group by Wilcoxon signed ranks test |
Click here to view
| Discussion|| |
Odontogenic tumors are lesions that are derived from the tooth forming tissues or their remnants that remain entrapped either within the jawbones or in the adjacent soft tissues.  No definite cause or stimulus has been elucidated in the etiopathogenesis of these tumors.  Ameloblastoma represents approximately 13-24% of all odontogenic tumors. , It is a benign, but a locally aggressive neoplasm.  Various factors have been associated with its aggressive behavior such as increase in the proliferative potential and changes in the expression of tumor suppressor genes and their protein products. ,
AOT is an uncommon tumor of odontogenic origin with a slow, progressive and circumscribed growth.  Considerable amount of debate is still ongoing whether it is a hamartoma or a neoplasm. The relative small size of the tumor and lack of recurrences in most cases support the fact that it is a hamartoma. On the contrary, early diagnosis of the lesion is considered to be a reason for its small size. 
There are several genes that play a role in the control of the G2/M phase of the cell cycle that are repressed by p53. Survivin is repressed at both RNA and protein levels by p53.  p53 interacts with the survivin promoter, which is demonstrated as the first promoter to confer p53-dependent repression. Survivin promoter is repressed by both direct (p53 binding) and indirect (induction of p21 protein) mechanisms. Each mechanism may depend on particular stress, phase of the cell cycle and cell type.  Thus, when p53 is mutated survivin is upregulated which not only promotes cell division but also inhibits apoptosis.
p53 expression was present in six out of ten tooth germs (60%). This was in contrast to previous studies where tooth germs failed to reveal any immunoreactivity to p53. ,,, The expression of p53 in the present study can be explained in response to various stresses such as oxidative stress, osmotic shock, heat shock, hypoxia, ribonucleotide depletion and deregulated oncogene expression in stressed cells of the tooth germ.  Under stress, certain proteins bind to Mdm2 or to the Mdm2/p53 complex, blocking p53 export to the cytoplasm and later preventing its degradation, resulting in the accumulation of p53 in the nucleus. 
Expression of p53 in normal mucosa has been attributed as an early event in carcinogenesis resulting from genetic alterations due to exposure to various carcinogens which over a period of time leads to cancer.  Thus, in the present study, expression of p53 in tooth germs could be an early event in the neoplastic transformation of the odontogenic epithelial cells similar to the expression of p53 in the normal oral epithelium.
Survivin expression was seen in five tooth germs out of ten (50%) in the present study which was similar to a study by Kumamoto and Ooya, where cytoplasmic expression of survivin was seen in IEE cells except for focal areas of nuclear staining in IEE cells in the present study. This may suggest that survivin is not only involved in cell survival during tooth development but also to an certain extent in cell division also.  Survivin is chiefly expressed in the undifferentiated proliferating cells such as stem cells, basal cells of the oral epithelium, embryonic and fetal tissues but becomes undetectable in most terminally differentiated cells.  Absence of survivin expression in five tooth germs may be due to differentiation of IEE cells into ameloblasts as hard tissue formation was evident in these tooth germs. However, there is no recent literature on the expression of survivin during late stages of tooth development.
No significant difference was seen in p53 expression between ameloblastoma and AOT (P = 0.554). This is in contrast to previous studies where significant difference has been reported in p53 expression in both the tumors. , Thus, AOT in the present study can be correlated to ameloblastoma in relation to p53. Gomes et al. performed HUMARA gene polymorphism assay on odontogenic tumors and suggested that AOTs are monoclonal and therefore neoplastic in nature and Garg et al. also accepted AOT as a true neoplasm. ,
Survivin exists in 5 different isoforms as a result of alternatively spliced transcripts: Survivin, Survivin-2B, Survivin-ΔEx3, Survivin-3B and Survivin-2α., Survivin and Survivin-2B are localized in the cytoplasm, particularly in mitochondria; Survivin-ΔEx3 is primarily nuclear, Survivin-2α is located in both the cytoplasm and nucleus and the subcellular localization of Survivin-3B remains to be determined. ,, These five survivin splicing variants and their unique subcellular compartmentalization create a delicate balance between induction and inhibition of the apoptotic process. , Survivin basically exists in two subcellular compartments as a result of the properties of different polypeptides specified by alternatively spliced transcripts.  Conflicting data is reported with respect to survivin expression in various tissues and tumors. In general, malignant tumors are characterized mainly by nuclear localization. ,, In this study, nuclear, cytoplasmic as well as combined survivin immunoreactivity was observed in both ameloblastoma and AOT.
Recent studies in the literature have described cytoplasmic expression of survivin to be associated with cell survival and nuclear expression with cell proliferation.  Thus, predominant cytoplasmic expression of survivin in the peripheral ameloblast-like cells in the present study can be correlated with its role in cell survival rather than in the proliferation of peripheral ameloblast-like cells. The presence of few ameloblast-like cells with nuclear survivin expression in the present study could probably suggest its sparse role in proliferative nature of ameloblastoma contributing to its benign but locally aggressive behavior.
The average percentage positivity for both nuclear and cytoplasmic expression of survivin was higher in ameloblastoma than AOT. Significant difference was detected among the studied groups suggesting that there could be a difference in the behavior of tumor cells in ameloblastoma and AOT with respect to evasion of apoptosis.
There was a significant difference in the expression of p53 and subcellular (nuclear and cytoplasmic) localization of survivin in AOT but only p53 and nuclear expression of survivin were significant in ameloblastoma. These results show variability in p53 and survivin expression in ameloblastoma and AOT [Table 3] and [Table 4]. However, due to predominant cytoplasmic expression of survivin and focal nuclear staining, there were no statistically significant differences in subcellular compartmentalization of survivin both in ameloblastoma and AOT.
The present study was done to explore the association of p53 and survivin in ameloblastoma and AOT for a better understanding about their different biological behavior. To the best of our knowledge, this is the first study highlighting the nuclear and cytoplasmic expression of survivin. A conclusion can be drawn that mutation of p53 upregulates survivin both in ameloblastoma and AOT. The predominant cytoplasmic staining of survivin suggests its role more as an antiapoptotic in these tumors rather than in cell division. Due to variable expression of p53 and subcellular localization of survivin between the tumors, the nature of AOT as a hamartoma or a neoplasm still remains obscure. Further studies have to be conducted using large sample size and molecular diagnostic tools and methods to elicit genetic profile of these lesions for better understanding of the mechanisms involved in tumorigenesis and behavior of these odontogenic tumors.
We wish to acknowledge Dr. Srinath Thakur, Principal, SDM College of Dental Sciences and Hospital, Dr. Kaveri Hallikeri, Professor and Head, Department of Oral Pathology, SDM College of Dental Sciences and Hospital, Dr. Amsavardani Tayaar @ Padmini. S, Professor, Department of Oral Pathology, SDM College of Dental Sciences and Hospital, Dr. M V Muddapur, Statistician, SDM College of Dental Sciences and Hospital, Dharwad, for their valuable support in the course of the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kumamoto H. Molecular pathology of odontogenic tumors. J Oral Pathol Med 2006;35:65-74.
de Oliveira MG, Lauxen Ida S, Chaves AC, Rados PV, Sant′Ana Filho M. Odontogenic epithelium: Immunolabeling of Ki-67, EGFR and survivin in pericoronal follicles, dentigerous cysts and keratocystic odontogenic tumors. Head Neck Pathol 2011;5:1-7.
Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, et al.
Control of apoptosis and mitotic spindle checkpoint by survivin. Nature 1998;396:580-4.
Kumamoto H, Ooya K. Expression of survivin and X chromosome-linked inhibitor of apoptosis protein in ameloblastomas. Virchows Arch 2004;444:164-70.
Melrose RJ. Benign epithelial odontogenic tumors. Semin Diagn Pathol 1999;16:271-87.
Crivelini MM, Soubhia AM, Felipini RC. Study on the origin and nature of the adenomatoid odontogenic tumor by immunohistochemistry. J Appl Oral Sci 2005;13:406-12.
Miller C, Mohandas T, Wolf D, Prokocimer M, Rotter V, Koeffler HP. Human p53 gene localized to short arm of chromosome 17. Nature 1986;319:783-4.
Yahya RS, Fouda MI, El-Baz HA, Mosa TE, Elmaksoud MD. Serum survivin and TP53 gene expression in children with acute lymphoblastic leukemia. Iran J Public Health 2012;41:37-44.
Hoffman WH, Biade S, Zilfou JT, Chen J, Murphy M. Transcriptional repression of the anti-apoptotic survivin gene by wild type p53. J Biol Chem 2002;277:3247-57.
Shi Y. Survivin structure: Crystal unclear. Nat Struct Biol 2000;7:620-3.
Altieri DC. The case for survivin as a regulator of microtubule dynamics and cell-death decisions. Curr Opin Cell Biol 2006;18:609-15.
Knauer SK, Mann W, Stauber RH. Survivin′s dual role: An export′s view. Cell Cycle 2007;6:518-21.
Stauber RH, Mann W, Knauer SK. Nuclear and cytoplasmic survivin: Molecular mechanism, prognostic, and therapeutic potential. Cancer Res 2007;67:5999-6002.
Knauer SK, Krämer OH, Knösel T, Engels K, Rödel F, Kovács AF, et al.
Nuclear export is essential for the tumor-promoting activity of survivin. FASEB J 2007;21:207-16.
Qi G, Tuncel H, Aoki E, Tanaka S, Oka S, Kaneko I, et al.
Intracellular localization of survivin determines biological behavior in colorectal cancer. Oncol Rep 2009;22:557-62.
Li F, Yang J, Ramnath N, Javle MM, Tan D. Nuclear or cytoplasmic expression of survivin: What is the significance? Int J Cancer 2005;114:509-12.
Mirza A, McGuirk M, Hockenberry TN, Wu Q, Ashar H, Black S, et al.
Human survivin is negatively regulated by wild-type p53 and participates in p53-dependent apoptotic pathway. Oncogene 2002;21:2613-22.
Schuler M, Bossy-Wetzel E, Goldstein JC, Fitzgerald P, Green DR. p53 induces apoptosis by caspase activation through mitochondrial cytochrome c release. J Biol Chem 2000;275:7337-42.
Zhang W, Hanks AN, Boucher K, Florell SR, Allen SM, Alexander A, et al.
UVB-induced apoptosis drives clonal expansion during skin tumor development. Carcinogenesis 2005;26:249-57.
Kumamoto H. Molecular alterations in the development and progression of odontogenic tumors. Oral Med Pathol 2010;14:121-30.
Lee SK, Kim YS. Current concepts and occurrence of epithelial odontogenic tumors: I. Ameloblastoma and adenomatoid odontogenic tumor. Korean J Pathol 2013;47:191-202.
Nodit L, Barnes L, Childers E, Finkelstein S, Swalsky P, Hunt J. Allelic loss of tumor suppressor genes in ameloblastic tumors. Mod Pathol 2004;17:1062-7.
Migaldi M, Sartori G, Rossi G, Cittadini A, Sgambato A. Tumor cell proliferation and microsatellite alterations in human ameloblastoma. Oral Oncol 2008;44:50-60.
Al-Fayad DW. Immunohistochemical expression of p53 in different types of ameloblastoma. Al Anbar Univ 2010;8:66-73.
Sandra F, Nakamura N, Kanematsu T, Hirata M, Ohishi M. The role of MDM2 in the proliferative activity of ameloblastoma. Oral Oncol 2002;38:153-7.
Kumamoto H, Izutsu T, Ohki K, Takahashi N, Ooya K. p53 gene status and expression of p53, MDM2, and p14 proteins in ameloblastomas. J Oral Pathol Med 2004;33:292-9.
Salehinejad J, Zare-Mahmoodabadi R, Saghafi S, Jafarian AH, Ghazi N, Rajaei AR, et al.
Immunohistochemical detection of p53 and PCNA in ameloblastoma and adenomatoid odontogenic tumor. J Oral Sci 2011;53:213-7.
Garg D, Palaskar S, Shetty VP, Bhushan A. Adenomatoid odontogenic tumor - Hamartoma or true neoplasm: A case report. J Oral Sci 2009;51:155-9.
Adamkov M, Halasova E, Rajcani J, Bencat M, Vybohova D, Rybarova S, et al.
Relation between expression pattern of p53 and survivin in cutaneous basal cell carcinomas. Med Sci Monit 2011;17:BR74-80.
el-Sissy NA. Immunohistochemical detection of p53 protein in ameloblastoma types. East Mediterr Health J 1999;5:478-89.
Al-Salihi KA, Li LY, Azlina A. p53 gene mutation and protein expression in ameloblastomas. Braz J Oral Sci 2006;5:1034-40.
Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991;253:49-53.
Olson MO, Dundr M. The moving parts of the nucleolus. Histochem Cell Biol 2005;123:203-16.
Sauter ER, Cleveland D, Trock B, Ridge JA, Klein-Szanto AJ. p53 is overexpressed in fifty percent of pre-invasive lesions of head and neck epithelium. Carcinogenesis 1994;15:2269-74.
Altieri DC. Survivin, versatile modulation of cell division and apoptosis in cancer. Oncogene 2003;22:8581-9.
Barboza CA, Pereira Pinto L, Freitas Rde A, Costa Ade L, Souza LB. Proliferating cell nuclear antigen (PCNA) and p53 protein expression in ameloblastoma and adenomatoid odontogenic tumor. Braz Dent J 2005;16:56-61.
Gomes CC, Oliveira Cda S, Castro WH, de Lacerda JC, Gomez RS. Clonal nature of odontogenic tumours. J Oral Pathol Med 2009;38:397-400.
Mahotka C, Wenzel M, Springer E, Gabbert HE, Gerharz CD. Survivin-deltaEx3 and survivin-2B: Two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer Res 1999;59:6097-102.
Caldas H, Honsey LE, Altura RA. Survivin 2alpha: A novel survivin splice variant expressed in human malignancies. Mol Cancer 2005;4:11.
Raj D, Brash DE, Grossman D. Keratinocyte apoptosis in epidermal development and disease. J Invest Dermatol 2006;126:243-57.
Piras F, Murtas D, Minerba L, Ugalde J, Floris C, Maxia C, et al.
Nuclear survivin is associated with disease recurrence and poor survival in patients with cutaneous malignant melanoma. Histopathology 2007;50:835-42.
Fortugno P, Wall NR, Giodini A, O′Connor DS, Plescia J, Padgett KM, et al.
Survivin exists in immunochemically distinct subcellular pools and is involved in spindle microtubule function. J Cell Sci 2002;115 (Pt 3):575-85.
Duffy MJ, O′Donovan N, Brennan DJ, Gallagher WM, Ryan BM. Survivin: A promising tumor biomarker. Cancer Lett 2007;249:49-60.
Adamkov M, Lauko L, Balentova S, Pec J, Pec M, Rajcani J. Expression pattern of anti-apoptotic protein survivin in dysplastic nevi. Neoplasma 2009;56:130-5.
Dr. Zulfin Shaikh
Department of Oral and Maxillofacial Pathology, Al-Badar Dental College and Hospital, Gulbarga, Karnataka
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]