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Molecular Etiopathogenesis of Ameloblastoma Current
Molecular Etiopathogenesis of Ameloblastoma Current
REVIEW ARTICLE
Department of Oral and Maxillofacial Pathology, SVS Institute of Dental Sciences, Mahabubnagar, Telangana, India, 2Departement of Dental Anatomy and Oral
Biology, College of Dentistry, Al Jouf University, Sakaka, Al Jouf, Kingdom of Soudi Arabia
Keywords
Ameloblastin, ameloblastoma, matrix
metalloproteinase, molecular and genetic
alterations, signaling molecules
Correspondence
Dr.S. Shylaja, SVS Institute of Dental
Sciences, Mahabubnagar, Telangana, India.
Phone: +91-9441023999, Email: eswardental@
rediffmail.com
Abstract
The ameloblastoma (AB) is a true neoplasm of enamel organ type tissue which does not
undergo dierentiation to the point of enamel formation. AB is locally invasive and recurs
despite adequate surgical removal. It is of varied origin, although the stimulus initiating
the process is unknown. The study of molecular and genetic alterations associated with
the development and progression of the AB will help to predict the course of the tumor
and lead to the development of new therapeutic concepts for their management. An
attempt has been made at compiling about molecular pathogenesis of AB.
Introduction
Ameloblastoma (AB) is the second most common benign
epithelial odontogenic tumor. ABs are clinically classified into
solid/multicystic, unicystic, desmoplastic, and peripheral types,
and based upon the pattern of arrangement of tumor cells they
may be divided into follicular, plexiform, acanthomatous, granular,
basal cell types, etc.[1] AB histologically resembles the epithelial
odontogenic apparatus, such as enamel organ and dental lamina, in
some respects; however, the detailed mechanism of oncogenesis,
cytodierentiation, and tumor progression remains unknown.
This review focuses on molecular and genetic alterations that
occur in AB which are helpful for better treatment and prognosis.
Clonality
Most odontogenic tumors are monoclonal in nature.[2] An
initial mutation/molecular alteration is the first event in the
development of the tumor. However, the sequence of events
remains unknown.[3]
Stem Cell Related Molecules
Kumamoto et al., (2010) analyzed the expression of stem cell
related molecules (Bmi-1, CD133, and ATP-binding cassette
Journal of Medicine, Radiology, Pathology & Surgery Vol. 1:2 Mar-Apr 2015
Etiopathogenesis of ameloblastoma
Spandana, et al.
Etiopathogenesis of ameloblastoma
Spandana, et al.
Etiopathogenesis of ameloblastoma
Spandana, et al.
Marker
Expression in AB
ABCG2,
Increased
CD-133, Bmi-1
Suggestive of
Oncogenesis
Cell differentiation
Malignant potential
Syndecan-1
Decreased
Aggressiveness
Invasiveness
51 integrin
Increased
Invasiveness
Podoplanin
Increased
Invasiveness through
collective cell migration
MT
Increased
Invasiveness
High recurrence
Ki-67
Increased in peripheral
cells
Aggressiveness
PCNA
Cyclin D1
Increased
Malignant transformation
Anti-apoptotic
(bcl-2, bcl-x)
Peripheral cells
Cytodifferentiation
Malignant transformation
Fas, FasL
Central cells in
Acanthomatous
and Granular cell
ameloblastoma
Cytodifferentiation
Neoplastic
transformation
Rb
Increased
PTEN
Increased
Aggressiveness
MMP-1,-2,-9
Increased
Aggressiveness
Invasiveness
PTHrP
Increased
Osteoclastogenesis tumor
expansion
PTCH1
Increased
Proliferation of
odontogenic epithelium
BMP-2,-4,-7
Increased
Cytodifferentiation
apoptotic cell death
-catenin
Increased
Cell migration
Conclusion
The development and progression of AB are aected by
alterations of many kinds of genes and molecules. Further
molecular studies, including genomic and proteomicbased profiling, are required to clarify the etiology and
pathogenesis of AB. A better understanding of underlying
molecular mechanisms will help to predict the course of AB and
lead to the development of new therapeutic applications such
as molecular-targeted treatment and patient-tailored therapy.
Invasiveness
Aggressiveness
Poor prognosis
Lymph node metastasis
Journal of Medicine, Radiology, Pathology & Surgery Vol. 1:2 Mar-Apr 2015
Etiopathogenesis of ameloblastoma
References
1. 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.
2. Gomes CC, Oliveira Cda S, Castro WH, de Lacerda JC,
GomezRS. Clonal nature of odontogenic tumours. JOral Pathol
Med 2009;38:397-400.
3. Gomes CC, Duarte AP, Diniz MG, Gomez RS. Current
concepts of ameloblastoma pathogenesis. J Oral Pathol Med
2010;39:585-91.
4. Kumamoto H, Ohki K. Detection of CD133, Bmi-1, and ABCG2
in ameloblastic tumors. JOral Pathol Med 2010;39:87-93.
5. Leocata P, Villari D, Fazzari C, Lentini M, Fortunato C,
Nictina PA. Syndecan-1 and Wingless-type protein-1 in
human ameloblastomas. JOral Pathol Med 2007;36:394-9.
6. Bologna-Molina R, Mosqueda-Taylor A, Lopez-Corella E,
Almeida OP, Carrasco-Daza D, Garcia-Vazquez F, et al.
Syndecan-1 (CD138) and Ki-67 expression in different subtypes
of ameloblastomas. Oral Oncol 2008;44:805-11.
7. Al-Otaibi O, Khounganian R, Anil S, Rajendran R. Syndecan-1
(CD 138) surface expression marks cell type and differentiation
in ameloblastoma, keratocystic odontogenic tumor, and
dentigerous cyst. JOral Pathol Med 2013;42:186-93.
8. Heikinheimo K, Morgan PR, Happonen RP, Stenman G,
Virtanen I. Distribution of extracellular matrix proteins in
odontogenic tumours and developing teeth. Virchows Arch B
Cell Pathol Incl Mol Pathol 1991;61:101-9.
9. Souza Andrade ES, da Costa Miguel MC, Pinto LP, de Souza LB.
Ameloblastoma and adenomatoid odontogenic tumor: The role
of alpha2beta1, alpha3beta1, and alpha5beta1 integrins in local
invasiveness and architectural characteristics. Ann Diagn Pathol
2007;11:199-205.
10. Gonzlez-Alva P, Tanaka A, Oku Y, Miyazaki Y, Okamoto E,
Fujinami M, et al. Enhanced expression of podoplanin in
ameloblastomas. JOral Pathol Med 2010;39:103-9.
11. Ribeiro AL, Nobre RM, Rocha GC, de Souza Lobato IH, de Melo
Alves Junior S, Jaeger RG, et al. Expression of metallothionein
in ameloblastoma. A regulatory molecule? J Oral Pathol Med
2011;40:516-9.
12. Johann AC, Caldeira PC, Souto GR, de Abreu MH, Aguiar MC,
Mesquita RA. Metallothionein immunoexpression in selected
benign epithelial odontogenic tumors. J Oral Pathol Med
2014;43:177-82.
13. Florescu A, Simionescu C, Ciurea R, Pitru A. P53, Bcl-2 and
Ki67 immunoexpression in follicular solid ameloblastomas.
Rom J Morphol Embryol 2012;53:105-9.
Journal of Medicine, Radiology, Pathology & Surgery Vol. 1:2 Mar-Apr 2015
Spandana, et al.