RESUMEN
Oestrogen receptor-binding fragment associated gene 9, EBAG9, is an oestrogen-responsive gene that was identified in MCF-7 human breast carcinoma cell line. It is identical to RCAS 1, a cancer cell surface antigen possibly involved in immune escape. In the present study, we examined the expression of EBAG9/RCAS1 in human epithelial ovarian cancer using immunohistochemistry, immunoblotting and reverse transcription-polymerase chain reaction (RT-PCR). A total of 90 epithelial ovarian cancer cases were examined immunohistochemically by means of the antibodies for EBAG9 and ERalpha. The correlation between EBAG9 immunoreactivity and clinicopathological parameters was examined. mRNA expression of EBAG9 and ERalpha were evaluated by RT-PCR in 22 cases. The expression for EBAG9 and ERalpha was examined by immunoblotting in 12 ovarian cancer cell lines. EBAG9 immunoreactivity was detected in the surface and cytoplasm of carcinoma cells in 46 out of 90 cases (51.1%). EBAG9 expression was significantly higher in serous histology (P=0.0402) and advanced disease (P=0.0206). No significant relationship was detected between EBAG9 immunoreactivity and overall survival (P=0.689). There was a highly significant correlation between EBAG9 and ER immunoreactivity (P<0.0001). The EBAG9 mRNA was detected in 20 out of 22 cases. In all of the cases that were positive for ERalpha mRNA, they were also positive for EBAG9 mRNA. Immunoreactive band corresponding to EBAG9 was detected in 11 out of 12 of ovarian cancer cell lines, and was consistent with ERalpha expression. In conclusion, the wide distribution of EBAG9 and its relation to advanced disease suggest that this protein may play important roles in epithelial ovarian cancer.
Asunto(s)
Antígenos de Neoplasias/genética , Antígenos de Neoplasias/farmacología , Perfilación de la Expresión Génica , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Femenino , Humanos , Immunoblotting , Inmunohistoquímica , Persona de Mediana Edad , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Androgen metabolism and possible actions are considered to play some roles in human epithelial ovarian neoplasms, but the details have not been well studied. We have examined the expression of 5alpha-reductase type 1 and type 2, which catalyze the conversion of testosterone to more active androgen, 5alpha-dehydrotestosterone, and androgen receptor (AR), using immunohistochemistry (104 cases) and reverse transcription-polymerase chain reaction (RT-PCR) (16 cases) as a first step toward understanding the metabolism and possible actions of androgens in human common epithelial ovarian carcinoma. 5alpha-Reductase type 1 was immunopositive in 75 / 104 cases (72.0%), and 5alpha-reductase type 2 in 52 / 104 cases (50.0%) (P < 0.001). There was no significant correlation between patterns of immunolocalization and clinicopathological parameters examined. Median labeling index (LI) for AR was 17.8% (range 0 - 84.4%) which was significantly higher in serous carcinoma than other histological types (P < 0.001). There was a significant positive correlation between 5alpha-reductase type 1 immunoreactivity and AR LI (P = 0.0027), but no significant correlation was detected in 5alpha-reductase type 2. Results of RT-PCR analysis were also consistent with those of immunohistochemistry. The relatively wide distribution of 5alpha-reductase type 1, and its correlation to AR status in human epithelial ovarian malignancies suggest that this isozyme plays important roles in androgen metabolism and actions in these tumors.
Asunto(s)
3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/biosíntesis , Adenocarcinoma de Células Claras/enzimología , Cistadenocarcinoma Mucinoso/enzimología , Cistadenocarcinoma Seroso/enzimología , Isoenzimas/biosíntesis , Proteínas de Neoplasias/biosíntesis , Neoplasias Hormono-Dependientes/enzimología , Neoplasias Ováricas/enzimología , Receptores Androgénicos/biosíntesis , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Adenocarcinoma de Células Claras/química , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Endometrioide/química , Carcinoma Endometrioide/enzimología , Cistadenocarcinoma Mucinoso/química , Cistadenocarcinoma Seroso/química , Femenino , Humanos , Isoenzimas/genética , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Estadificación de Neoplasias , Neoplasias Hormono-Dependientes/química , Neoplasias Ováricas/química , ARN Mensajero/análisis , ARN Neoplásico/análisis , Receptores Androgénicos/genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Progesterone receptor (PR) is a member of the nuclear receptor superfamily. To date, two isoforms of PR have been identified, PR-A and PR-B. In progesterone responsive tissues, the relative ratio of PR-A and PR-B is considered to contribute to the tissue-specific actions of progesterone. In this study, we examined the distribution of PR-A and PR-B in human fetal tissues ranging from 11 to 40 gestational weeks using immunohistochemistry and RT-PCR analysis. PR immunoreactivity was detected in a wide range of fetal tissues until 20 weeks of gestation, but gradually decreased towards the late gestational period. However, PR continued to remain positive throughout the gestational period in the interstitial cells of Cajal and endocrine tissues. PR-B was demonstrated as the predominant isoform in comparison to PR-A in all fetal tissues examined. These findings suggest that progesterone may be involved in the development of fetal organs throughout the gestational period.
Asunto(s)
Desarrollo Embrionario y Fetal , Receptores de Progesterona/metabolismo , Células Enteroendocrinas/química , Feto/citología , Feto/metabolismo , Feto/fisiología , Edad Gestacional , Humanos , Inmunohistoquímica , Intestinos/citología , Intestinos/embriología , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/fisiología , ARN Mensajero/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Distribución TisularRESUMEN
The expression of 5alpha-reductase types 1 and 2 was examined in human breast carcinoma using immunohistochemistry and RT-PCR. Immunoreactivity for 5alpha-reductase isozymes was also correlated with various clinicopathological parameters to examine possible local regulatory mechanisms of sex steroids, including progesterone and androgens, in human breast carcinoma tissues. Immunoreactivity for 5alpha-reductase type 1 was detected in the cytoplasm and possibly in the nuclear membrane of tumor cells in 35 of 60 invasive ductal carcinomas (58%), and type 2 signal was detected in 9 of these 60 cases (15%). The results from RT-PCR (n = 8) were consistent with those from immunohistochemistry. A significant positive correlation was detected between 5alpha-reductase type 1 immunoreactivity and androgen and progesterone receptor A or B labeling indexes, and immunoreactivities of 5alpha-reductase type 2, 17beta-hydroxysteroid dehydrogenase type 5, or 3beta-hydroxysteroid dehydrogenase, which recognizes both types I and II. An inverse correlation was detected between 5alpha-reductase type 1 immunoreactivity and tumor size, histological grade, or Ki-67 labeling index. 5alpha-Reductase type 2 immunoreactivity was significantly correlated with 17beta-hydroxysteroid dehydrogenase type 5 immunoreactivity, but not with other parameters. This study suggests that 5alpha-reductase type 1 is mainly expressed in human breast carcinoma, which may play an important role in the in situ production and actions of the potent androgen, 5alpha-dihydrotestosterone, including inhibition of cancer cell proliferation, in hormone-dependent human breast carcinoma.
Asunto(s)
3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/metabolismo , Neoplasias de la Mama/enzimología , Carcinoma Ductal de Mama/enzimología , Dihidrotestosterona/metabolismo , Isoenzimas/metabolismo , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , 3-Hidroxiesteroide Deshidrogenasas/metabolismo , 3-Oxo-5-alfa-Esteroide 4-Deshidrogenasa/genética , Adulto , Anciano , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Femenino , Humanos , Inmunohistoquímica , Isoenzimas/genética , Persona de Mediana Edad , Receptores Androgénicos/análisis , Receptores de Progesterona/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: In the present study, we conducted a multicenter retrospective analysis to elucidate the prognostic factors of stage IV epithelial ovarian cancer. METHODS: In November 1999, 24 Japanese institutions received questionnaires regarding stage IV epithelial ovarian cancer patients. Eligibility criteria included all patients with stage IV epithelial ovarian cancer who were surgically confirmed and initially treated in each institution between January 1990 and December 1997. Data were collected regarding age, performance status, tumor histologic subtype, site of metastasis, preoperative CA125, cytoreductive surgery, residual disease after cytoreductive surgery, and response to primary chemotherapy. Survival analysis and comparisons were performed by univariate and multivariate methods. RESULTS: Two hundred twenty-five patients with stage IV ovarian cancer were identified. The median age of the patients was 54 years. The most common site of extraperitoneal disease was malignant pleural effusion (39.6%). Of the 225 patients who underwent an attempt at surgical debulking, 70 (31.1%) were optimally cytoreduced. Most patients received platinum-based combination chemotherapy for primary chemotherapy. In multivariate analysis, performance status, histology, and residual disease after cytoreductive surgery were independent prognostic predictors of outcome. The overall median survival for optimally debulked patients was 32 months compared to 16 months for suboptimally debulked patients (P < 0.0001, hazard ratio: 0.415). CONCLUSION: Optimal surgical debulking, performance status, and histology appear to be important prognostic factors of survival in patients with stage IV epithelial ovarian cancer.