Gestational Trophoblastic Disease (GTD) encompasses a spectrum of disease that involves abnormal trophoblastic proliferation. It includes hydatidiform mole (HM), placental site trophoblastic tumor (PSTT), epithelioid trophoblastic tumor (ETT) and choriocarcinoma (CCA). While HMs are abnormal pregnancies with limited invasive potential, CCAs are true malignancies requiring chemotherapy. Although the majority of HM is resolved by surgical intervention, approximately 8-30% of them would develop into persistent GTD. In addition to that, being the most aggressive neoplasm in GTD, choriocarcinoma is a frankly malignant gestational trophoblastic neoplasm (GTN) that could be arisen from HM and could be fetal when widespread metastasis is developed. However, the underlying mechanisms of this disease progression are still unclear. FBI-1 (Factor that Binds to Inducer of Short Transcripts (IST) protein 1) is a transcription factor that has been observed to be overexpressed in various types of human cancers. Recently, overexpression of FBI-1 is also reported in GTD and also in association with GTN development. However, the causes of FBI-1 overexpression in GTD are still unclear. This study aims to investigate gene amplification as a possible cause of FBI-1 overexpression in GTD. A quantitative real time PCR (qPCR) assay was established and was used to investigate ZBTB7A (the gene encoding FBI-1) amplification in GTD cell lines and clinical samples. Using our qPCR assay, we demonstrated that ZBTB7A is not amplified in the CCA cell lines JEG-3 and JAR, in comparison with an immortalized trophoblast cell line HTR-8/SVneo. Testing ZBTB7A amplification in clinical samples also obtained similar findings although overexpression of FBI-1 was demonstrated in our previous studies. This is the first report illustrating absence of ZBTB7A amplification in cells with FBI-1 overexpression. There are other techniques that can detect gene amplification and/or other genetic and epigenetic mechanisms that may govern FBI-1 expression in GTD. Further studies will be worthwhile to pursue as FBI-1 is a potential target for cancer therapy. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

published_or_final_version / abstract / Anatomy / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

No description available.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (M. Med. Sc.)--University of Hong Kong, 2006.

Resumo: Traçar um padrão de distribuição geográfica da doença trofoblástica gestacional (DTG) em centro de referência do estado da Bahia, no Nordeste do Brasil e determinar as características demográficas na apresentação da doença. Estudo observacional descritivo com dados obtidos de prontuários de 140 pacientes com DTG encaminhadas ao Centro de Doença Trofoblástica Gestacional da Maternidade Climério de Oliveira, no estado da Bahia, Brasil, de 2002 a 2007. Foi feita uma distribuição geográfica das pacientes com DTG, nas macrorregiões de saúde e foram avaliadas variáveis demográficas, fonte de referência, e tipo de gestação antecedente. Para análise estatística foi usado teste qui-quadrado (p<0,05%). A principal procedência das pacientes foi da macrorregião de saúde Leste (77,9%). A incidência da DTG no centro de referência foi de 8,5/1.000 partos. A faixa etária foi predominante de 20 a 34 anos (65%). Uma pequena proporção de pacientes estava trabalhando (42,9%). O nível educacional foi baixo: 67,9% das pacientes cursaram apenas o ensino fundamental. Hospitais secundários foram a principal fonte de referência de pacientes (84,3%). A maioria das pacientes teve gestação de termo prévia à DTG (42,1%). Neste estudo, a DTG predominou na melhor faixa etária para fecundidade e em pacientes com aspectos sócio-demográficos desfavoráveis. A tendência de referência dessas pacientes foi principalmente da macrorregião de saúde Leste. / Abstract: To outline the geographical distribution pattern of gestational trophoblastic disease (GTD) in a referral center located in the state of Bahia, northeastern Brazil, and to determine the demographic characteristics in the presentation of the disease. Observational, descriptive study of the data retrieved from the medical records of 140 GTD patients referred to the Gestational Trophoblastic Disease Center of Climério de Oliveira Maternity, Bahia, Brazil between 2002 and 2007. The geographical distribution of GTD patients across healthcare macroregions was determined and demographic variables, referral sources and type of previous gestation were assessed. Statistical analysis was performed using the chi-square test (p<0.05%). Results: The majority of the patients originated from the East Healthcare Macroregion (77.9%). DTG incidence at the referral Center was 8.5/1.000 deliveries. The 20-34-year age group predominated (65%). A small percentage of the patients was employed (42.9%). Education level was low: 67.9% of the patients attended only elementary school. Secondary hospitals were the principal sources of patient referral (84.3%). In most cases (42.1%), GTD was preceded by term gestation. DTG predominated in the peak fertility age group and among patients of unfavorable socio-demographic status. Most referred patients tended to come from the East Healthcare Macroregion. / Orientador: Marilza Vieira Cunha Rudge / Coorientador: Izildinha Maestá / Coorientador: Olívia Lúcia Nunes Costa / Banca: Raul Cortes Charry / Banca: Sue Iazaki Sua / Mestre

Orientador: Izildinha Maestá / Banca: Izildinha Maestá / Banca: Sue Yazaki-sun / Banca: José Carlos Peraçoli / Resumo: Objetivo: avaliar a utilidade da curva de regressão normal da gonadotrofina coriônica humana no diagnóstico de neoplasia trofoblástica pós molar (NTG). Metodologia: Foi construída curva de regressão normal considerando-se a média e o limite superior de confiança a 95% dos valores quinzenais de -hCG sérico de 80 pacientes com mola hidatiforme completa (MHC) e remissão espontânea. Nesta curva de regressão normal foram identificados o primeiro valor de -hCG acima do limite superior de confiança a 95% das 25 pacientes com MHC e evolução para NTG. Curvas individuais das 105 pacientes foram estabelecidas e analisadas sobre a curva de regressão normal, verificando-se o comportamento destas curvas. Os valores de 3-hCG que excederam o limite superior da curva normal foram considerados anormais. Resultados: As 25 pacientes que desenvolveram NTG pós-molar tiveram desvio da curva de regressão normal de 3-hCG em 3,84 l 2,57 semanas, enquanto platô ou ascensão ocorreu em 8,40 l 2,94 semanas, pós-esvaziamento uterino, com diferença significativa (p< 0,001). Do total de 25 pacientes com MHC e evolução para NTG, 20 (80%) apresentaram valores de -hCG acima do limite superior da curva de regressão normal dentro de quatro semanas, pós-esvaziamento uterino, enquanto nenhuma apresentou platô ou ascensão. Em seis semanas pós esvaziamento uterino, 23 pacientes com NTG (92%) apresentaram valores anormais, acima do limite superior da curva de regressão normal, enquanto somente 11 (44%) mostraram evolução com platô ou ascensão. Houve diferença no comportamento das curvas individuais dos dois grupos quando analisadas sobre a curva de regressão normal. Conclusões: A identificação de pacientes com MHC e evolução para NTG é mais rápida através da curva de regressão normal de 3-hCG, comparada ao platô ou ascensão. A curva de regressão normal de -hCG é útil no diagnóstico precoce de NTG pós molar. / Abstract: To evaluate the usefulness of the normal 3-human chorionic gonadotrophin (p-hCG) regression curve in the diagnosis of post-molar trophoblastic neoplasia (PMTN). Methods: The normal regression curve was constructed by taking into account the mean and the 95% confidence limit of the bi-weekly values of serum 3-hCG from 80 patients with uneventful complete hydatidiform mole. In this normal regression curve, the first í3-hCG value over the 95% confidence upper limit of the 25 patients with complete hidatidiform mole (CHM) and the development to PMTN were identified. Individual curves of the 105 patients were established and analyzed over the normal regression curve, and the behavior of such curves was analyzed. The 3-hCG values exceeding the upper limit of the normal curve were regarded as abnormal. Results: The 25 patients who developed PMTN showed a devíance in the -hCG normal regression curve in 3.84 l 2.57 weeks while the plateau or increase occurred in 8.40 l 2.94 weeks after evacuation with a significant difference (p< 0.001). Of the total of 25 patients with CHM and development to PMTN, 20 (80%) showed -hCG values over the normal regression curve upper limit within four weeks postevacuation while none showed a plateau or increase. In six weeks post-uterine emptying, 23 patients with PMTN (92%) showed abnormal values over the normal regression curve upper limit while only 11(44%) showed development with a plateau or increase. A difference was noted in the behavior of indívidual curves in the two groups when they were analyzed over the normal regression curve. Conclusions: The identification of patients with CHM and development to PMTN is quicker when using the -hCG normal regression curve as compared to the plateau or increase. The -hCG normal regression curve is useful in the early diagnosis of post-molar NTG. / Mestre

published_or_final_version / Pathology / Doctoral / Doctor of Philosophy