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3.
Zhonghua Bing Li Xue Za Zhi ; 45(8): 505-6, 2016 Aug 08.
Artículo en Chino | MEDLINE | ID: mdl-27510771
4.
Carcinogenesis ; 30(1): 114-21, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18796737

RESUMEN

Endometrial and ovarian cancers are the most common and the most lethal gynecologic malignancies worldwide, respectively. By performing differential expression analysis using annealing control primer-based reverse transcription (RT)-polymerase chain reaction (PCR) on pooled complementary DNA (cDNA) from 45 endometrial and 36 ovarian cancers and their non-tumor samples, reduced expression of the follistatin-like 1 (FSTL1) was identified. Downregulation of FSTL1 was further confirmed on individual samples and cell lines by quantitative real-time RT-PCR and western blotting. For in vitro functional study, full-length cDNA of FSTL1 was cloned and transiently transfected into the ovarian cancer cell line Ovca420 and endometrial cancer cell line AN3CA. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and cell count demonstrated significantly slower proliferation rate. By terminal uridine deoxynucleotidyl transferase dUTP nick end labeling and flow cytometric analysis, higher apoptotic activity and a remarkable increase in sub-G(1) cell population were observed in transfected cells, suggesting that FSTL1 induced apoptosis in cancer cells. Subsequent messenger RNA and protein expression analysis on downstream apoptotic molecules revealed upregulation and/or activation of FAS, FASLG, TRADD, Caspase-3, Caspase-7 and PARP by FSTL1 transfection, suggesting that FSTL1-induced apoptosis may be initiated mainly by FAS/FASLG death receptor-ligand binding. Cell migration and invasion assays demonstrated a remarkably lower cell migration and invasion capability in FSTL1-transfected cells in relation to downregulation of matrix metallopeptidase-2. Our findings suggested that a tumor suppressor role of FSTL1 may be important in ovarian and endometrial carcinogenesis.


Asunto(s)
Neoplasias Endometriales/fisiopatología , Proteínas Relacionadas con la Folistatina/fisiología , Genes Supresores de Tumor , Neoplasias Ováricas/fisiopatología , Apoptosis , Western Blotting , Proliferación Celular , Regulación hacia Abajo , Neoplasias Endometriales/patología , Femenino , Citometría de Flujo , Proteínas Relacionadas con la Folistatina/genética , Humanos , Etiquetado Corte-Fin in Situ , Invasividad Neoplásica , Metástasis de la Neoplasia , Neoplasias Ováricas/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
5.
Histopathology ; 52(2): 167-74, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18184265

RESUMEN

AIMS: Hydatidiform mole (HM) is the most common type of gestational trophoblastic disease. A proportion of patients with HM develop gestational trophoblastic neoplasia (GTN) requiring chemotherapy. The aim was to identify differentially expressed genes that are associated with development of GTN. METHODS AND RESULTS: Using cDNA microarray, differential expression of prostate stem cell antigen (PSCA) was identified in HMs that developed GTN compared with those that spontaneously regressed. Significant overexpression of PSCA RNA (P = 0.037) and protein (P < 0.05) in aggressive HM was verified by real-time polymerase chain reaction (PCR) and immunohistochemical analysis in 10 first-trimester placentas, 36 HM that subsequently regressed and 11 HM that developed GTN. A high level of PSCA expression was also found in three choriocarcinomas and three placental site trophoblastic tumours. A positive correlation was observed between PSCA expression and proliferation and apoptotic indices as assessed by Ki67 (P = 0.01), mcm7 (P = 0.001) and M30 (P = 0.016), as well as p53 (P < 0.01), p21(WAF1/CIP1) (P < 0.01) and mdm2 (P = 0.002) expression. CONCLUSIONS: Overexpression of PSCA is associated with development of GTN in HM. PSCA probably plays a role in the regulation of cell growth through p53-related signaling pathways.


Asunto(s)
Enfermedad Trofoblástica Gestacional/metabolismo , Mola Hidatiforme/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias de la Próstata/metabolismo , Adolescente , Adulto , Antígenos de Neoplasias , Biomarcadores de Tumor/metabolismo , Proliferación Celular , ADN de Neoplasias/genética , Femenino , Proteínas Ligadas a GPI , Regulación Neoplásica de la Expresión Génica , Enfermedad Trofoblástica Gestacional/genética , Enfermedad Trofoblástica Gestacional/patología , Humanos , Mola Hidatiforme/genética , Mola Hidatiforme/patología , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Embarazo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Transducción de Señal/genética , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
6.
Histopathology ; 51(4): 477-83, 2007 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17880529

RESUMEN

AIMS: To investigate p63 expression in ovarian neoplasms. METHODS AND RESULTS: Immunohistochemistry using an antibody that detects all p63 isoforms was performed on 103 primary ovarian neoplasms of different histological types. Diffuse nuclear immunoreactivity of p63 was demonstrated in the 17 benign and five borderline Brenner tumours. Only one of the six malignant Brenner tumours displayed p63 expression. p63 immunoreactivity was absent in all the ovarian transitional cell carcinomas (TCC), but was demonstrated extensively in TCCs of the urinary bladder. Besides focal p63 expression in epidermal basal cells of immature and mature teratomas, all other ovarian lesions were devoid of p63 expression. p63 expression was also demonstrated in cervical transitional cell metaplasia and Walthard cell nests of fallopian tubes. CONCLUSIONS: Expression of p63 protein is apparently cell lineage specific and in ovarian neoplasms is confined to benign and borderline Brenner tumours. The loss of expression in malignant Benner tumours suggests a role for p63 in Brenner carcinogenesis. The distinct patterns of p63 expression in TCCs in the ovary and urinary bladder may help in their differential diagnosis.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Tumor de Brenner/metabolismo , Carcinoma de Células Transicionales/metabolismo , Proteínas de la Membrana/metabolismo , Neoplasias Ováricas/metabolismo , Tumor de Brenner/diagnóstico , Tumor de Brenner/patología , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/patología , Diagnóstico Diferencial , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas de la Membrana/genética , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Pronóstico
7.
Br J Cancer ; 95(8): 1087-91, 2006 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-17047655

RESUMEN

Mitochondrial DNA (mtDNA) content in ovarian carcinomas was assessed by quantitative PCR. Results show that mtDNA content in tumour cell was significantly higher than that in normal ovary. Change in mtDNA content was not related with patients' age or tumour stages. However, the average mtDNA copy number in pathological low-grade tumours was over two-fold higher than that in high-grade carcinomas (P=0.012). Moreover, type I carcinomas also had a significantly higher mtDNA copy number than in type II carcinomas (P=0.019). Change in mtDNA content might be an important genetic event in the progression of ovarian carcinomas.


Asunto(s)
ADN Mitocondrial/genética , Neoplasias Ováricas/patología , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patología , Adulto , Anciano , Cistadenocarcinoma Mucinoso/genética , Cistadenocarcinoma Mucinoso/patología , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patología , Replicación del ADN/genética , ADN Mitocondrial/metabolismo , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/genética
8.
Carcinogenesis ; 27(7): 1502-6, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16574671

RESUMEN

Epidemiological studies suggested that ovulation was associated with ovarian carcinogenesis. Follicle-stimulating hormone (FSH) played an important role in follicular development and was recently found to affect growth of ovarian epithelial cells. Single nucleotide polymorphisms (SNPs) Thr307Ala and Asn680Ser were two non-synonymous variations in the coding region of the FSH receptor (FSHR) gene. This hitherto first case-control study investigating the association between these two FSHR SNPs and the risk of ovarian cancer involved 202 histopathologically confirmed ovarian cancer patients and 266 age-matched cancer-free control subjects using restriction fragment length polymorphism assay and direct sequencing. Our results demonstrated that the 307Ala and 680Ser carriers were associated with significantly increased risk of developing serous and mucinous types of ovarian cancers (P < 0.0005, OR = 2.60, 95% CI = 1.56-4.34; and P < 0.0005, OR = 2.89, 95% CI = 1.73-4.84, adjusted for age, respectively) but not endometrioid and clear cell types. The two SNPs were found to be in modest linkage disequilibrium, D' = 0.804 and 0.701, r2 = 0.581 and 0.406 for the cancer and control groups, respectively. The major haplotype of 307Ala-680Ser was also associated with higher cancer risk (P = 0.033, OR = 1.39, 95% CI = 1.03-1.88), especially for the serous and mucinous carcinomas (P = 0.001, OR = 1.82, 95% CI = 1.27-2.60). Our results suggested that the two FSHR SNPs might affect the susceptibility of women to specific subtypes of ovarian cancer. Different types of ovarian cancer might adopt distinct carcinogenetic pathways. Such understanding may be important in selecting patients for ovulation induction therapy.


Asunto(s)
Predisposición Genética a la Enfermedad , Neoplasias Ováricas/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de HFE/genética , Secuencia de Bases , Estudios de Casos y Controles , Femenino , Humanos , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Factores de Riesgo
9.
J Clin Pathol ; 59(8): 845-50, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16461808

RESUMEN

BACKGROUND: All-trans retinoic acid (ATRA) is a natural vitamin A derivative that has a profound effect on the regulation of cell growth, differentiation and death. AIM: To investigate the tissue dynamic and cellular invasion effects of ATRA in choriocarcinoma (CCA), an aggressive trophoblastic tumour, by using a three-dimensional organotypic culture model system and cell invasion assay, respectively. METHODS: An organotypic culture model of two CCA cell lines, JAR and JEG, was established. The effects of 1 microM ATRA on proliferation, differentiation and apoptosis on this CCA model were assessed by morphological assessment of the mitotic and apoptotic figures as well as by Ki-67 and caspase-related M30 cytoDeath antibody immunohistochemistry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay. The effect of ATRA on p53 and its regulated protein product, WAF1/Cip1, was also evaluated with DO7 and p21(WAF1) antibodies, respectively. Moreover, the effect of ATRA on cellular (CCA) invasion was also investigated with Cell Invasion Kit on the JEG cell line. RESULTS: ATRA was found to induce marked apoptosis in organotypic cultures of both cell lines, as evidenced by increased M30-positive cells (p<0.0001) and increased TUNEL-positive cells (p<0.0001) in treated cultures; to decrease proliferation, as evidenced by decreased Ki-67-positive cells (p<0.0001); and to decrease p53-DO7 immunoreactivity (p<0.0001) and increase p21(WAF1) (p<0.0001) immunoreactivity. 1.5 microM ATRA was found to effectively inhibit JEG cell invasion in the cell invasion assay. CONCLUSION: ATRA treatment was found to inhibit invasion and proliferation and enhance apoptosis, probably by the activation of caspases and induction of differentiation. ATRA and synthetic retinoids may be alternative agents for the treatment of CCA.


Asunto(s)
Antineoplásicos/farmacología , Coriocarcinoma/patología , Tretinoina/farmacología , Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Coriocarcinoma/metabolismo , Relación Dosis-Respuesta a Droga , Humanos , Etiquetado Corte-Fin in Situ/métodos , Proteína p53 Supresora de Tumor/metabolismo
10.
J Clin Pathol ; 59(2): 179-83, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16443735

RESUMEN

BACKGROUND: Placental trophoblast can be considered to be pseudomalignant tissue and the pathogenesis of gestational trophoblastic diseases remains to be clarified. AIMS: To examine the role of caspases 8 and 10, identified by differential expression, on trophoblast tumorigenesis. METHODS: cDNA array hybridisation was used to compare gene expression profiles in choriocarcinoma cell lines (JAR, JEG, and BeWo) and normal first trimester human placentas, followed by confirmation with quantitative real time polymerase chain reaction and immunohistochemistry. Caspase 10 and its closely related family member caspase 8 were analysed. RESULTS: Downregulation of caspase 10 in choriocarcinoma was detected by both Atlastrade mark human cDNA expression array and Atlastrade mark human 1.2 array. Caspase 10 mRNA expression was significantly lower in hydatidiform mole (p = 0.035) and chorioarcinoma (p = 0.002) compared with normal placenta. The caspase 8 and 10 proteins were expressed predominantly in the cytotrophoblast and syncytiotrophoblast, respectively, with significantly lower expression in choriocarcinomas than other trophoblastic tissues (p < 0.05). Immunoreactivity for both caspase 8 and 10 correlated with the apoptotic index previously assessed by terminal deoxynucleotidyl transferase mediated dUTP nick end labelling (p = 0.02 and p = 0.04, respectively) and M30 (p < 0.001 and p = 0.003, respectively) approaches. CONCLUSIONS: These results suggest that the downregulation of capases 8 and 10 might contribute to the pathogenesis of choriocarcinoma.


Asunto(s)
Caspasas/biosíntesis , Coriocarcinoma/enzimología , Regulación Neoplásica de la Expresión Génica , Neoplasias Uterinas/enzimología , Apoptosis , Caspasa 10 , Caspasa 8 , Caspasas/genética , Coriocarcinoma/patología , ADN de Neoplasias/genética , Regulación hacia Abajo , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Mola Hidatiforme/enzimología , Mola Hidatiforme/patología , Hibridación de Ácido Nucleico , Análisis de Secuencia por Matrices de Oligonucleótidos , Placenta/enzimología , Embarazo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Células Tumorales Cultivadas , Neoplasias Uterinas/patología
11.
Placenta ; 27(4-5): 521-6, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16026829

RESUMEN

Complete hydatidiform mole (CHM) is a type of gestational trophoblastic disease with pure paternal chromosome contribution and unpredictable malignant potential. As an attempt to assess the molecular pathogenesis of CHM, suppression subtractive hybridization (SSH) combined with cDNA microarray was used to compare the gene expression pattern of CHM compared with normal first-trimester placenta of similar gestational ages. cDNA microarray analysis using tissue-specific chips constructed with subtracted cDNA libraries identified 13 differentially expressed gene transcripts. Quantitative real-time polymerase chain reaction (PCR) confirmed up-regulation of human chorionic gonadotropin beta subunit (CGB) (P=0.0008) and KIAA1200 (P=0.0005), a G-protein regulator, as well as down-regulation of osteopontin (SPP1) (P<0.0001) in 14 genotyped CHM when compared with 15 normal placentas. These candidate genes may contribute toward understanding the mechanism involved with the development and progression of CHM.


Asunto(s)
Mola Hidatiforme/metabolismo , Adulto , Estudios de Casos y Controles , Gonadotropina Coriónica Humana de Subunidad beta/metabolismo , Regulación hacia Abajo , Femenino , Proteínas de Unión al GTP/metabolismo , Perfilación de la Expresión Génica/métodos , Humanos , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Osteopontina , Placenta/metabolismo , Reacción en Cadena de la Polimerasa , Embarazo , Trimestres del Embarazo , Análisis de Secuencia de ADN , Sialoglicoproteínas/metabolismo , Regulación hacia Arriba
12.
Histopathology ; 47(3): 303-9, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16115231

RESUMEN

AIMS: To assess the expression of Id proteins in trophoblastic tissues and to correlate this with clinical parameters, proliferative and apoptotic indices as well as to related oncogene expression. METHODS AND RESULTS: Immunohistochemistry for Id1, Id2, Id3 and Id4 was performed on 83 trophoblastic tissues including 17 normal first-trimester placentas, seven term placentas, 47 hydatidiform moles (HM), and 12 spontaneous miscarriages. The four Id proteins were predominantly expressed in the villous and implantation site intermediate trophoblast. Expression of Id1 in HM was significantly higher than that in normal placenta (P = 0.0006) and spontaneous miscarriage (P = 0.0001) but did not correlate with subsequent development of gestational trophoblastic neoplasia (GTN). Id1 expression correlated with the proliferation index as assessed by MCM7 (P = 0.003) and Ki67 (P = 0.017) and with the apoptotic activity assessed by TUNEL (P = 0.001) and M30 CytoDeath antibody (P = 0.013). Moreover, the expression of Id1 correlated with the expression of p53 (P = 0.004), p21(WAF1) (/CIP1) (P = 0.003) but not with p16 (P = 0.107). CONCLUSIONS: Id proteins may play a role in the regulation of proliferative and apoptotic activity in trophoblastic tissue and are potentially useful in differentiating molar and non-molar gestation, but are not helpful in predicting GTN.


Asunto(s)
Mola Hidatiforme/patología , Proteínas Represoras/biosíntesis , Factores de Transcripción/biosíntesis , Proteínas de Ciclo Celular/análisis , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Femenino , Secuencias Hélice-Asa-Hélice , Humanos , Mola Hidatiforme/metabolismo , Inmunohistoquímica , Proteína 1 Inhibidora de la Diferenciación , Placenta/química , Embarazo , Trofoblastos/química , Trofoblastos/patología , Proteína p53 Supresora de Tumor/análisis
13.
Histopathology ; 46(3): 307-13, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15720416

RESUMEN

AIMS: To assess, in tissue microarray (TMA), the proliferative activity of endometrial carcinoma using one of the minichromosome maintenance (MCM) proteins (MCM7), and to explore its potential value for prognosis. MCM proteins are essential for eukaryotic DNA replication and have recently been used to define the proliferative compartments in human tissues. METHODS AND RESULTS: Immunohistochemistry for MCM7 and Ki67 was performed on TMAs constructed from 212 cases of endometrial carcinoma. MCM7 and Ki67 expression was quantified according to the extent of nuclear staining. An analysis was carried out of the association between MCM7 expression and that of Ki67 and the clinicopathological characteristics of endometrial carcinoma. MCM7 and Ki67 immunoreactivity was clearly evident in the nuclei of tumour cells. MCM7 and Ki67 labelling indices in endometrial carcinomas correlated with each other (P < 0.001). A significant correlation existed between the MCM7 labelling index and histological grade (P = 0.008) and patients' age at diagnosis (P < 0.001). Well-differentiated carcinomas and younger patients had a lower MCM7 index. Poor survival was observed in patients with endometrial carcinoma with a high MCM7 index (P = 0.03) and MCM7 was found to be an independent prognostic factor by multivariate analysis (P = 0.04). The Ki67 labelling index correlated with histological grade (P = 0.01) but had no significant prognostic impact (P = 0.50). CONCLUSIONS: In this TMA study on endometrial carcinoma, MCM7 was found to be a more reliable and useful marker than Ki67 in assessing tumour proliferation and in the prognosis of patients.


Asunto(s)
Biomarcadores de Tumor/análisis , Proteínas de Ciclo Celular/análisis , Proteínas de Unión al ADN/análisis , Neoplasias Endometriales/patología , Proteínas Nucleares/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Proliferación Celular , Replicación del ADN , Neoplasias Endometriales/metabolismo , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Persona de Mediana Edad , Componente 7 del Complejo de Mantenimiento de Minicromosoma , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Análisis de Supervivencia , Análisis de Matrices Tisulares
14.
Int J Gynecol Cancer ; 13(6): 879-88, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-14675328

RESUMEN

The clinical significance of cadherins in gestational trophoblastic diseases (GTD) is not fully understood. In this study, the expression of E-cadherin and cadherin-11 in 12 normal placentas, 32 cases of hydatidiform mole (HM) including 15 complete HMs and 17 partial HMs, and five choriocarcinomas was investigated by immunohistochemistry and correlated with follow-up of HMs. Cases with available frozen blocks were further analyzed by western blot and semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR). Methylation of E-cadherin was investigated by methylation-specific PCR in six normal first trimester placentas, 19 HMs and their associated deciduas. E-cadherin expression was localized to cytotrophoblast and intermediate trophoblast whereas cadherin-11 was expressed in syncytiotrophoblast, intermediate trophoblast, and decidua. Immunoreactivity of E-cadherin was reduced in choriocarcinoma and complete HM when compared with that in normal first trimester placenta (P < 0.01, P = 0.04). Hypermethylation of E-cadherin was demonstrated in three complete HMs with the lowest level of E-cadherin. Compared with normal first trimester placenta, immunoreactivity of cadherin-11 was higher in complete HM (P = 0.02), but lower in choriocarcinoma (P = 0.02). Such differential expression was confirmed by western blot and semiquantitative RT-PCR. No obvious association was observed between the development of persistent trophoblastic disease with the expression of E-cadherin and cadherin-11.


Asunto(s)
Cadherinas/biosíntesis , Cadherinas/metabolismo , Coriocarcinoma/genética , Coriocarcinoma/patología , Regulación Neoplásica de la Expresión Génica , Enfermedad Trofoblástica Gestacional/genética , Enfermedad Trofoblástica Gestacional/patología , Mola Hidatiforme/genética , Mola Hidatiforme/patología , Neoplasias Uterinas/genética , Neoplasias Uterinas/patología , Adulto , Western Blotting , Femenino , Humanos , Inmunohistoquímica , Metilación , Placenta/fisiología , Embarazo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
15.
Histopathology ; 43(5): 485-90, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14636275

RESUMEN

AIMS: To assess the proliferative activity of gestational trophoblastic disease (GTD) using one of the novel proliferation markers (MCM7) and to determine its prognostic value in hydatidiform mole (HM). METHODS AND RESULTS: Immunohistochemical staining for MCM7 was performed on 122 samples of paraffin-embedded trophoblastic tissues including 22 normal first-trimester placentas, 12 term placentas, 12 spontaneous miscarriages (SM), 21 partial moles (PM), 44 complete hydatidiform moles (CM), and 11 choriocarcinomas (CCA). The correlations between the proliferative indices assessed by MCM7, proliferating cell nuclear antigen (PCNA) and Ki67 (MIB1) immunoreactivity as well as clinical progress were assessed. MCM7 immunoreactivity was found predominantly in the nuclei of cytotrophoblast and intermediate trophoblast and decreased with placental maturation. MCM7 expression was highest in CCA, followed by CM, PM, normal first-trimester placenta, SM and term placenta. MCM7 index was significantly higher in PM and CM than in SM (P = 0.007, P < 0.001) but not between PM and CM themselves (P = 0.560). Eighteen of the 65 patients with HM developed persistent trophoblastic disease (PTD) requiring chemotherapy. There was no significant difference in MCM7 indices between the patients who developed PTD and those who did not (P = 0.312). MCM7 indices correlated well with Ki67 (P = 0.002) but not with PCNA (P = 0.054) indices. MCM7 indices demonstrated less variability than PCNA and Ki67 and may be a better proliferation marker than the latter two. CONCLUSIONS: We conclude that MCM7 is useful in differentiating molar and non-molar gestations but is not helpful in discriminating PM from CM or in predicting PTD.


Asunto(s)
Biomarcadores de Tumor/análisis , Enfermedad Trofoblástica Gestacional/metabolismo , Enfermedad Trofoblástica Gestacional/patología , Antígeno Ki-67/biosíntesis , Antígeno Nuclear de Célula en Proliferación/biosíntesis , Femenino , Humanos , Inmunohistoquímica , Placenta/metabolismo , Placenta/patología , Embarazo , Pronóstico
16.
Hum Mutat ; 19(3): 307-8, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11857749

RESUMEN

Previous mutational analysis for BRCA gene mutations in sporadic ovarian cancer occurring in Chinese patients in Hong Kong identified six germline BRCA1 mutations and one germline BRCA2 mutation, six of which were novel (Khoo et al., 2000). Knowledge of BRCA gene mutations in the Chinese population is relatively scant. In this study, we focussed on whether any of these mutations could be recurrent in our Chinese population, making use of archival paraffin embedded tissue. A consecutive series of 214 ovarian cancer cases, half of Southern Chinese origin from Hong Kong whilst the other half of Northern Chinese origin from Beijing were used for the study. We identified one further novel mutation, 1081delG, in BRCA1. This was found to occur in two unrelated individuals with shared haplotype as revealed by allelotype analysis, thus demonstrating founder effect. Two other recurrent mutations were also identified, the 2371-2372delTG mutation in BRCA1 and the 3337C>T mutation in BRCA2 recurring in two and three unrelated individuals respectively, giving an overall prevalence 4.7% of recurrent BRCA mutations in ovarian cancer in the Southern Chinese population. Most importantly, all our recurrent mutation carriers were identified from Southern Chinese patients from Hong Kong whilst such mutations were absent in samples from the Northern Chinese. Our findings indicate possible heterogeneity in the BRCA genotype between Northern and Southern Chinese. The identification of a founder mutation and two recurrent mutations moreover, has important implications towards screening strategies for breast and ovarian cancer among Chinese of southern ancestral origin who are now dispersed throughout the world.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Carcinoma/genética , Efecto Fundador , Genes BRCA1 , Genes BRCA2 , Mutación de Línea Germinal/genética , Neoplasias Ováricas/genética , Adulto , Anciano , Carcinoma/patología , China/etnología , Femenino , Genética de Población , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/patología , España/epidemiología
17.
Eur J Cancer ; 37(9): 1104-10, 2001 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-11378340

RESUMEN

The inhibitor of apoptosis proteins (IAP) suppress apoptosis induced by a variety of stimuli. The aims of this study were to: (a) compare the expression of X-linked IAP (Xiap) and Human IAP-2 (Hiap-2) in cervical carcinoma cells and normal cervix, (b) determine the correlation between IAP expression and tumour apoptosis or proliferation, and (c) assess their prognostic significance in cervical carcinomas. Paraffin-embedded tissue sections were retrieved from 77 patients with cervical squamous carcinomas prior to treatments and 47 normal subjects. Tumour apoptosis was determined by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuracil triphosphate (dUTP) nick-end labelling (TUNEL) and apoptotic index (AI), and the proliferative rate was measured by Ki-67 and mitotic (MI) indices. Immunoreactive Xiap and Hiap-2 were found in both cervical cancer cells and normal tissues. IAP expressions in cancers did not correlate with apoptotic and proliferative parameters, disease stage and patient survival. The lower AI and Ki-67 index were associated with a better survival. In conclusion, the basal expression levels of IAPs have no prognostic significance, but AI and Ki-67 expression are potential prognostic indicators in cervical carcinoma.


Asunto(s)
Carcinoma de Células Escamosas/patología , Neoplasias del Cuello Uterino/patología , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/fisiología , División Celular , Femenino , Humanos , Inmunohistoquímica , Etiquetado Corte-Fin in Situ/métodos , Antígeno Ki-67/análisis , Persona de Mediana Edad , Mitosis/fisiología , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia
18.
Cancer ; 91(5): 1052-60, 2001 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-11251959

RESUMEN

BACKGROUND: Primary peritoneal malignant mixed Müllerian tumors (MMMTs) are rarely reported in the literature. METHODS: The clinical, pathologic, and immunohistochemical features of five cases of MMMT of female peritoneum were analyzed. The tumors were also investigated for expression of hormone receptors, specific BRCA-1 mutations, and clonality. RESULTS: The patients' ages ranged from 33 to 67 years. They presented with abdominal pain or mass. One case of peritoneal MMMT was associated with a synchronous endometrial carcinoma whereas another case was detected 2 years after the diagnosis of a primary adenocarcinoma of the fallopian tube. One patient died 1 month after diagnosis whereas 2 patients died with disease within 1 year. Both carcinomatous and sarcomatous elements are present in all the tumors. Squamous differentiation was noted in two cases. Heterologous elements, including chondroid, rhabodomyoblastic, and osteoid differentiation were detected in all tumors. Immunohistochemical studies confirm the biphasic differentiation with variable demonstration of neural and smooth muscle differentiation. All five MMMTs were negative for estrogen and progestogen receptors although the related endometrial and tubal carcinomas were positive. Heteroduplex analysis used to screen for specific BRCA-1 mutations were negative in all five MMMTs. Clonality study of the two MMMTs found in association with endometrial carcinoma and tubal carcinoma was inconclusive. CONCLUSIONS: Our study confirmed that primary peritoneal MMMTs were aggressive tumors with poor prognosis. The presence of synchronous or metachronous genital carcinomas suggests multifocal tumorigenesis from tissue of same embryologic origin. The lack of hormone receptor in these tumors indicates deviation from hormonal control. Specific BRCA-1 mutations found in ovarian carcinoma in Chinese patients could not be detected in our series.


Asunto(s)
Tumor Mulleriano Mixto/patología , Neoplasias Peritoneales/patología , Adulto , Anciano , Diferenciación Celular , Transformación Celular Neoplásica , Análisis Mutacional de ADN , Cartilla de ADN , ADN de Neoplasias/análisis , Progresión de la Enfermedad , Femenino , Genes BRCA1/genética , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Tumor Mulleriano Mixto/genética , Tumor Mulleriano Mixto/inmunología , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/inmunología , Reacción en Cadena de la Polimerasa , Pronóstico
20.
Int J Gynecol Pathol ; 17(4): 351-7, 1998 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-9785136

RESUMEN

The chromosomal composition of cancers arising in ovarian mature cystic teratoma (MCT) was analyzed using chromosome in situ hybridization (CISH) performed on paraffin-embedded material from 10 squamous cell carcinomas, 1 adenocarcinoma, 1 thyroid papillary carcinoma, and 1 strumal carcinoid. Cervical tissue from seven of these patients was used as a control. In the cancers, a relative gain of chromosome 16 (in 7 cases), chromosome 12 (in 9), chromosome 11 (in 10), and chromosome X (in 8) was detected. Trisomy 12 was diagnosed in eight cases. No chromosomal aberrations were detected in the strumal carcinoid. In the benign areas of the MCTs, only one case showed a gain of chromosome 11, although, in another case, there was a gain of chromosome X. Malignant transformation of MCTs often occurs in association with complex chromosome aberrations that may play a role in the development of such carcinomas.


Asunto(s)
Transformación Celular Neoplásica/genética , Aberraciones Cromosómicas , Neoplasias Ováricas/genética , Teratoma/genética , Adenocarcinoma/genética , Adulto , Anciano , Anciano de 80 o más Años , Tumor Carcinoide/genética , Carcinoma Papilar/genética , Carcinoma de Células Escamosas/genética , Cromosomas Humanos Par 11 , Cromosomas Humanos Par 12 , Cromosomas Humanos Par 16 , Femenino , Humanos , Hibridación in Situ , Persona de Mediana Edad , Neoplasias de la Tiroides/genética , Cromosoma X
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