Immunohistochemical Detection of Nerve Growth Factor Expression in Follicular and Plexiform Ameloblastoma

Renuga Devi, S (2020) Immunohistochemical Detection of Nerve Growth Factor Expression in Follicular and Plexiform Ameloblastoma. Masters thesis, Vivekanandha Dental College for Women, Tiruchengode.


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Title: Immunohistochemical detection of Nerve Growth Factor (NGF) expression in follicular and plexiform ameloblastoma. INTRODUCTION: Odontogenic tumours (OT) are lesions derived from the epithelial and/or mesenchymal elements of the tooth forming apparatus and are therefore found exclusively within the jaw bones. OTs are not frequently occurring lesions accounting for < 2–3% of all oral and maxillofacial specimens sent for diagnosis to oral pathology services. If viewed as a percentage of all tumours in the human body, this figure is reduced to a conservative estimate of approximately 0.002–0.003%. Ameloblastoma is an aggressive odontogenic tumour that forms from odontogenic epithelium within a mature fibrous stroma devoid of odontogenic ectomesenchyme. At present, it is known that the potential sources to develop an ameloblastoma are varied, and these include: • Cell rests of enamel organ, • Epithelium of existing odontogenic cyst, • Disturbances of the developing enamel organ, • Basal cells of the surface epithelium of the jaws. Although classified as a benign tumour, ameloblastoma is also the most common odontogenic tumour of epithelial origin with severe clinical implications. Ameloblastoma has a locally aggressive growth pattern; about 70% of cases undergo malignant transformation, and up to 2% metastasize to other sites. Ameloblastoma constitutes about 14% of all jaw tumours and cysts, and it is the most prevalent odontogenic tumours in developing countries. The tumor shows an approximately equal prevalence in the third to seventh decades of life. Ameloblastoma has two relatively distinct cells, an anti-apoptotic proliferating site in the periphery (Ameloblast like cells) and a pro-apoptotic differentiating site in the centre (Stellate reticulum like cells) resembling the enamel organ during odontogenesis. The molecular background of ameloblastoma has been poorly understood, thus hindering the development of noninvasive therapies. The neurotrophins and neurotrophin receptors plays a major role in apoptosis, survival, and differentiation of neural and non-neural cells. The neurotrophin family comprises four different members. The first of these growth factors to be described was the neuronal growth factor (NGF), followed by the discovery of the brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4/5 (NT-4/5). The actions mediated by these molecules depend on their binding to two different subsets of transmembrane receptors. On one side, the pro-neurotrophins (immature form of these factors) and mature neurotrophins bind to the p75 neurotrophin receptor (p75NTR), and on the other, only mature neurotrophins bind to three different tropomyosin-related kinase (TrK A, TrK B, TrK C) receptors in a specific manner. In this way, NGF binds to TrKA, BDNF and NT-4/5 to TrKB, and NT-3 to TrkC. Following ligand binding, p75NTR can act independently or p75NTR can also act as a TrK co-receptor, allowing a stronger binding affinity of the neurotrophins to the TrK receptors. p75NTR and TrK receptors can interact both in synergistic or antagonistic manners. The formation of a p75NTR/TrK complex was shown to facilitate the affinity and selectivity of each neurotrophin for its TrK receptor. AIM OF THE STUDY: 1. The study is aimed at evaluating the expression of Nerve Growth Factor in follicular and plexiform ameloblastoma. Objectives: 2. To detect and analyze the immunohistochemical expression pattern of Nerve Growth Factor in follicular type of ameloblastoma. 3. To detect and analyze the immunohistochemical expression pattern of Nerve Growth Factor in plexiform type of ameloblastoma. 4. To compare the immunohistochemical expression pattern of Nerve Growth Factor among the follicular and plexiform types of ameloblastoma. JUSTIFICATION: 1. High and low affinity neurotrophin receptors namely TrK and p75NTR along with neurotrophin signalling pathways, plays a crucial role for survival/proliferation regulating pathways (RAS, MAPK, P13, IKK and NFkB) of the neuronal and non-neuronal cells prove p75NTR independent, p75NTR dominant or TrK dominant system. 2. Expression of RAS, MAPK, P13K, IKK, and NFkB have been elucidated in other tumours by the binding of nerve growth factor ligand with nerve growth factor receptors through earlier studies. 3. Expression of P75NTR in peripheral Ameloblast like cells of Ameloblastoma has already been documented in literature. This study will detect the role of nerve growth factor and its possible role in the biological behaviour of ameloblastoma METHODOLOGY: • 40 paraffin embedded study samples will be extracted from the archives of the Department of Oral Pathology and Microbiology, Vivekananda Dental College for Women, Tiruchengode. • The study sample comprises of follicular and plexiform types of ameloblastoma. • The selected samples will be sectioned into two sections of 3 to 5 microns. One section will be stained with haematoxylin and eosin (H&E), and the other will be Immunohistochemically stained with NGF marker. • In all samples, under H&E staining, when morphological analysis disclosing the presence of more than one histological pattern of Ameloblastoma, then the pattern which predominates will be considered for final diagnosis. • Immunohistochemical standardisation will be done using nervous tissue as positive control. Immunohistochemical reactivity is classified into three groups:(+) mildly positive, (++) moderately positive and (++) strongly positive. • Inclusion criteria - histological patterns of Follicular and plexiform types of Ameloblastoma. • Exclusion criteria - hybrid Ameloblastoma, other histological variants of Ameloblastoma and recurrent Ameloblastoma. STATISTICAL ANALYSIS: Statistical package for social science SPSS version 16 will be used. The scores for strongly positive immunoreactivity will be given between 6 and 9, for moderate positive immunoreactivity between score 2 and 3, and for weakly positive immunoreactivity, score 1 and 2 will be given [Nunia et al., 2016]. [50] An unpaired t-test will be used to compare the staining intensity between follicular and plexiform ameloblastoma and a Chi-square Test will be employed to determine the magnitude of expression between follicular and plexiform ameloblastoma. Potential Risk: There is no potential risk. BENEFITS: Histological diagnosis via IHC will bring us to a non-surgical approach of the treatment of ameloblastoma in the near future. OUTCOME MEASURES: By obtaining thorough knowledge on the altered molecular signalling pathways in this neoplasia, we can definitely elucidate the mechanisms of tumorigenesis, cell differentiation, and tumour progression.

Item Type: Thesis (Masters)
Additional Information: 241721452
Uncontrolled Keywords: Immunohistochemical Detection, Nerve Growth Factor Expression, Follicular, Plexiform Ameloblastoma.
Subjects: DENTAL > Oral Pathology and Microbiology
Depositing User: Subramani R
Date Deposited: 24 Feb 2021 16:52
Last Modified: 24 Feb 2021 16:52

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