Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 132-174) Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2008. / Also available online.

Thesis (M. Phil.)--University of Hong Kong, 2008.

Thesis (Ph. D.)--University of Hong Kong, 2008. / Includes bibliographical references (leaf 132-174) Also available online.

Thesis (Ph. D.)--Ohio State University, 2005. / Document formatted into pages; contains xviii, 169 p. Includes bibliographical references. Abstract available online via OhioLINK's ETD Center; full text release delayed at author's request until 2006 March 9.

Thesis (Ph.D.) - University of Queensland, 2002. / Includes bibliography.

Thesis (M.Phil.) - University of Queensland, 2005. / Includes bibliography.

Perineural invasion (PNI) in cutaneous squamous cell carcinoma (cSCC) and desmoplastic melanoma (DM) may be a negative prognostic finding, and likely contributes to increased rates of local recurrence. The biological mechanisms underlying PNI remain unclear, although several lines of evidence implicate neurotrophins and their receptors. Expression of the high affinity nerve growth factor (NGF) receptor TrkA has been shown to be associated with PNI in numerous malignancies, although literature in cutaneous neoplasms is sparse. Given this, we sought to ascertain the incidence of PNI in a cohort cSCCs using double immunostaining (DIS), and to investigate PNI's relationship with TrkA expression and established histopathologic prognosticators. In DMs we investigated the relationship between TrkA and PNI. In DM we additionally analyzed expression of the low affinity NGF receptor (p75NGFR) and the presence of a functional polymorphism in the glial cell line-derived neurotrophic factor (GDNF) receptor RET (RETp) as they relate to PNI. In this IRB approved study, cSCCs from the head and neck (H&N) and 53 from non-H&N areas were immunohistochemically analyzed for PNI (DIS with S100 and p63) and TrkA expression. For DM, 43 cases were immunohistochemically evaluated for TrkA and p75NGFR expression while RETp was detected by direct DNA sequencing. The presence of each was correlated with histologically observed PNI. In cSCCs, comparing H&N versus non-H&N areas; using hemotoxylin and eosin (H&E) PNI was detected in 11% versus 6% of cases respectively and using DIS, in 23% versus 15% respectively, with significant disagreement between both methods (𝜅=0.47, p=0.002). There was a 2.33 fold increase in PNI detection with DIS compared to H&E (95%CI: 1.12-4.87; p=0.02). TrkA expression was 2.9 times more frequently observed in cSCCs from the H&N compared to those from non-H&N areas (p=0.01). Regardless of site, TrkA expression was associated with decreased degree of differentiation (OR=6.46, p=0.0006) and high-risk morphologic variants (OR = 6.53, p=0.002). TrkA expression was not significantly associated with PNI (p=0.33). In DM, PNI was present in 67% of cases. On univariate analysis; p75NGFR was associated with PNI (expression detected in 79% of PNI-positive cases compared to 36% of PNI-negative cases, p=0.005), increased Breslow's depth and greater Clark's Level (p= 0.007 and p= 0.01 respectively). RETp was noted in 28% of cases but was not significantly associated with PNI (p=0.27) or other histopathologic variables. TrkA expression was absent in all cases. PNI was associated with increased Breslow's depth and Clark's Level (p=0.01 and p=0.009 respectively). Controlling for the association between p75NGFR and depth, p75NGFR remained associated with an increased propensity for PNI (OR=4.68, p=0.04). In conclusion, increased PNI detection with DIS in cSCCs underscores the adjunctive utility of immunohistochemistry in microstaging. Although unlikely to play a role in the development of PNI, TrkA's association with cSCCs from H&N and select histopathologic parameters suggests a role for the NGF-TrKA axis in tumorogenesis while its absent expression in DM suggests that expression is lineage-related. Lastly, In DM, p75NGFR expression is significantly associated with PNI and a more locally aggressive phenotype.

Magister Scientiae Dentium - MSc(Dent) / Background: Recent epidemiological reports established that there is an increase in the incidence of oral squamous cell carcinoma in young patients. Some report this to be in the absence of contributing habits such as smoking and alcohol use. Few reports of such a nature have reported a similar trend in South Africa. Aim: Describe the epidemiological pattern of oral squamous cell carcinoma seen at the Tygerberg academic complex. Method: Histopathological biopsy reports of patients diagnosed by the oral pathology department of Tygerberg hospital from 1996 to 2013 were electronically retrieved and included. Patients were grouped by age into two groups, one included patients 40 years and younger, the other included patients older than 40 years. Descriptive analysis was performed for age, sex, smoking and alcohol habits and oral site of tumor. Frequency of OSCC patients was calculated manually from the total number of oral biopsies. Chi- square or Fisher’s exact tests were used as appropriate. Probabilities of less than 0.05 were regarded as significant. Results: The total number of OSCC patients over the 18-year period was 2220. The mean age was 57.6years.The male to female ratio was 2.9:1 for all age groups and 2.2:1 for young patients. The majority of patients (96%) were above 40 years old. Smoking and alcohol were commonly reported for all age groups (91.3%) and (83.8%) for young patients. The tongue was the commonest site for all age groups (30.8%) followed by oropharynx (27.3%) while in younger patients, the oropharynx was the commonest site (30.3%) followed by tongue (29.2%). Conclusion: The study confirmed that OSCC is still an affliction of people older than 40 years and males are predominantly affected. Smoking and alcohol are strong risk factors for OSCC irrespective of patient's age. OSCC among people older than 40 years may have no great difference from the same disease affecting younger ones in terms of sex, oral habits and tumor site.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A boca pode ser acometida por doenÃas, variando de alteraÃÃes de desenvolvimento à neoplasias malignas agressivas e metastatizantes. O conhecimento destas condiÃÃes auxilia no diagnÃstico diferencial realizado pelo clÃnico. Este trabalho tem como objetivo realizar uma anÃlise epidemiolÃgica das lesÃes de cavidade oral em cinco laboratÃrios de anÃtomo patologia da cidade de Fortaleza, CearÃ, Brasil. MÃtodos: Coleta de dados a partir de laudos histopatolÃgicos de lesÃes orais, no perÃodo de 2001 a 2005, oriundos de cinco laboratÃrios, de anatomia patolÃgica, pÃblicos e privados. As variÃveis utilizadas foram sexo, idade, raÃa, localizaÃÃo anatÃmica e laudo histopatolÃgico. As lesÃes analisadas foram agrupadas em nÃo-neoplÃsicas, neoplÃsicas e laudos descritivos. Resultados: No perÃodo analisado, foram coletadas 6231 lesÃes orais, das quais 41,41% oriundas de laboratÃrios particulares e 58,59% de laboratÃrios pÃblicos. O sexo feminino foi o mais acometido, com proporÃÃo homem:mulher de 1:1,68. As lesÃes ocorreram em uma ampla faixa etÃria, variando de 0 a 100 anos, com pico de incidÃncia entre 31 e 60 anos. As lesÃes nÃo-neoplÃsicas representaram 64,89% dos casos, com as lesÃes inflamatÃrias/reativas sendo as mais prevalentes, seguidas pelas lesÃes inflamatÃrias de glÃndula salivar, cistos e hiperplasias epiteliais sem atipias. As neoplasias representaram 30,80% dos casos, das quais 59,52% eram benignas, 32,45% malignas e 8,03% eram lesÃes prÃ-malignas. A hiperplasia fibroepitelial foi a lesÃo mais prevalente em todo o estudo e o carcinoma de cÃlulas escamosas, a neoplasia maligna mais comum, com 23,14% e 8,52% respectivamente ConclusÃo: As lesÃes foram mais comuns no sexo feminino, na faixa etÃria economicamente ativa, representadas principalmente por lesÃes inflamatÃrias/reativas. Apesar da alta ocorrÃncia de lesÃes inflamatÃrias/reativas neste estudo, a prevalÃncia de lesÃes malignas foi significativa, demonstrando a necessidade do conhecimento destas lesÃes pelo cirurgiÃo dentista e a criaÃÃo de polÃticas pÃblicas que enfatizem a prevenÃÃo e o diagnÃstico precoce das mesmas / A wide range of diseases can affect the oral cavity, from developmental defects to metastasizing malignant neoplasms. The knowledge on Oral Pathologies`s prevalence helps the clinician making differential diagnosis. The aim of this study was to perform an epidemiological survey of oral lesions in five anatomopathological laboratories in Fortaleza, CearÃ, Brazil. Methods: The sample was obtained from histopathology reports of oral lesions diagnosed between the years of 2001 to 2005 in five anatomopathological laboratories. Data regarding sex, race, age, anatomical site and histopathological diagnosis were registered. Lesions were categorized in non-neoplastic, neoplastic and descritive reports. Results: During the five-year period, 6231 oral lesions reports were collected, 41,41% from private laboratories and 58,59% from public laboratories. Female were more affected, with a male:female ratio of 1:1,68. Lesions occurred in a wide age range, varying from 0 to 100 years old, with an incidence peak between 31 to 60 years. Non-neoplastic lesions represented 64,89% of cases, with inflammatory/reactive lesions being the most prevalent group, followed by inflammatory lesions of salivary glands, cysts and non-atypical epithelial hyperplasia. Neoplastic lesion represented 30,80% of cases, 59,52% benign, 32,45% malignant and 8,03% pre-malignant lesions. Fibroepithelial hyperplasia was the most common lesion in this study and squamous cell carcinoma was the most prevalent malignant neoplasm, with 23,14% and 8,52%, respectively. Conclusions: Oral lesions were more common among femaleâs reports, in economically active age, mainly represented by inflammatory/reactive lesion. Although, the occurrence of inflammatory/reactive lesions was high, the prevalence of malignant neoplastic and pre-malignant lesion was significant. There dental surgeon must know about the occurrence of such lesions, and public health politics for prevention and early diagnose must be enfasized