Análise da expressão dos receptores de estrogênio, progesterona e EAR3 (COUP-TFI) em neoplasias epiteliais ovarianas e ovários normais
Arquivos
Data
2007
Autores
Damiao, Roberio de Sousa 
Orientadores
Goncalves, Wagner Jose
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Os hormônios sexuais estão envolvidos na carcinogênese de algumas
neoplasias ginecológicas, seus receptores estão implicados como
indicadores de prognóstico e resposta terapêutica em neoplasias de mama
e endométrio. No ovário, este papel não está claramente definido;
neoplasias epiteliais são consideradas pouco responsivas a terapêutica
hormonal. COUP-TFI (Fator transcricional I de ovalbumina) são receptores
nucleares órfãos, sinalizadores de processos biológicos, expressados em
vários tecidos e que regulam o receptor de estrogênio (ER) por competição
com DNA. Para investigar sua participação na carcinogênese ovariana e
implicação no prognóstico, avaliamos, por imunohistoquímica a expressão
dos receptores de estrogênio (ER), progesterona (PR) e COUP-TFI em
neoplasias epiteliais ovarianas benignas, malignas e ovários normais.
Analisamos 113 espécimes de ovários, sendo 40 com diagnóstico de
neoplasia epitelial maligna (Grupo A), 45 com neoplasia epitelial benigna
(Grupo B) e 28 com ovários normais (Grupo C). Houve imunoexpressão do
ER em 70% das pacientes do Grupo A, 57,8% do Grupo B e 57,1 % do
Grupo C; sem diferença estatística entre os mesmos (p=0,426). No Grupo
A, a imunoexpressão do PR foi de 12,5%, no Grupo B 42,2% e no Grupo C
32,1%; com diferença significativamente menor no Grupo A em relação aos
demais (p=0,010). De forma semelhante, COUP-TFI expressou-se em
apenas 10% do Grupo A e significativamente menor em relação ao Grupo
B 31,1% e Grupo C 39,3% (p=0,014). Não houve associação entre a
expressão destes marcadores, aumento da sobrevida ou variáveis clínicas
de prognóstico. Análise multivariada no Grupo A, destacou a neoplasia
residual menor que 1cm como a variável clínica de maior significado
estatístico (p=0,010) em relação ao prognóstico (OR=4,14). Estes dados
reforçam a importância da citorredução no tratamento da neoplasia de
ovário e o papel dos receptores esteróides no mecanismo de
carcinogênese e seleção de subgrupos que possam responder à
terapêutica hormonal.
Sex hormones are involved in the carcinogenesis of some gynecologic cancers and the status of their receptors represents an indicator of prognosis and of the therapeutic response in breast and endometrial cancers. In the ovary, this role is not clearly defined, with epithelial cancers being poorly responsive to hormone therapy. COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I) is an orphan nuclear receptor, which is expressed in various tissues and regulates the estrogen receptor (ER) by competition for DNA binding. To investigate the role of these receptors in ovarian carcinogenesis and their implications for cancer prognosis, we evaluated the immunohistochemical expression of ER, progesterone receptor (PR) and COUP-TFI in benign and malignant ovarian epithelial neoplasms and in normal ovaries. A total of 113 ovarian specimens, including 40 with a diagnosis of malignant epithelial neoplasms (group A), 45 with benign epithelial tumors (group B), and 28 from normal ovaries (group C) were analyzed. Immunoexpression of ER was observed in 70% of patients of group A, 57.8% of group B and 57.1% of group C, with no significant difference between groups (P=0.426). Immunoexpression of PR was significantly lower in group A (12.5%) compared to group B (42.2%) and group C (32.1%) (P=0.010). Similarly, COUP-TFI was expressed in only 10% of group A patients, a rate significantly lower than that observed for group B (31.1%) and group C (39.3%) (P=0.014). No association was observed between the expression of these markers and increased survival or clinical prognostic variables. Multivariate analysis revealed a residual tumor smaller than 1 cm as the most significant clinical prognostic factor in group A (P=0.010, OR=4.14). These data support the importance of cytoreduction in the treatment of ovarian cancer, the role of steroid receptors in the mechanism of carcinogenesis, and the need for selection of subgroups that may respond to hormone therapy.
Sex hormones are involved in the carcinogenesis of some gynecologic cancers and the status of their receptors represents an indicator of prognosis and of the therapeutic response in breast and endometrial cancers. In the ovary, this role is not clearly defined, with epithelial cancers being poorly responsive to hormone therapy. COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I) is an orphan nuclear receptor, which is expressed in various tissues and regulates the estrogen receptor (ER) by competition for DNA binding. To investigate the role of these receptors in ovarian carcinogenesis and their implications for cancer prognosis, we evaluated the immunohistochemical expression of ER, progesterone receptor (PR) and COUP-TFI in benign and malignant ovarian epithelial neoplasms and in normal ovaries. A total of 113 ovarian specimens, including 40 with a diagnosis of malignant epithelial neoplasms (group A), 45 with benign epithelial tumors (group B), and 28 from normal ovaries (group C) were analyzed. Immunoexpression of ER was observed in 70% of patients of group A, 57.8% of group B and 57.1% of group C, with no significant difference between groups (P=0.426). Immunoexpression of PR was significantly lower in group A (12.5%) compared to group B (42.2%) and group C (32.1%) (P=0.010). Similarly, COUP-TFI was expressed in only 10% of group A patients, a rate significantly lower than that observed for group B (31.1%) and group C (39.3%) (P=0.014). No association was observed between the expression of these markers and increased survival or clinical prognostic variables. Multivariate analysis revealed a residual tumor smaller than 1 cm as the most significant clinical prognostic factor in group A (P=0.010, OR=4.14). These data support the importance of cytoreduction in the treatment of ovarian cancer, the role of steroid receptors in the mechanism of carcinogenesis, and the need for selection of subgroups that may respond to hormone therapy.
Descrição
Citação
DAMIãO, Robério de Sousa. Análise da expressão dos receptores de estrogênio, progesterona e EAR3 (COUP-TFI) em neoplasias epiteliais ovarianas e ovários normais. 2007. 115 f. Tese (Doutorado em Ciências) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2007.